StemCell Therapy

Of the nearly 4 million women in the United States who have had either breast cancer or ovarian cancer, at least 1.5 million have a high risk of carrying certain types of genetic mutations that could increase their risk for additional cancers in the future.

And although the mutations, including those that affect the BRCA1 and BRCA2 genes, can be identified through a simple blood or saliva test, more than 80 percent of those women have not taken the test or even discussed it with a health care provider, according to a new study from the UCLA Fielding School of Public Health.

The study is published online August 18 in the peer-reviewed Journal of Clinical Oncology.

"Many of these women have inherited genetic changes that put them and their family members at risk for future cancers," said Dr. Christopher Childers, a resident physician in the department of surgery at the David Geffen School of Medicine at UCLA and the study's lead author. "Identifying a mutation is often important for surgical decision-making and cancer therapy, but its importance extends further than that. If individuals are aware that they have these mutations, they can take steps to lower their future cancer risk."

Childers said people who know they have the mutations would be advised to undergo more frequent and specialized screening (such as breast MRI), consider preventive medications, undergo risk-reducing surgery or make lifestyle modifications (including improving diet and exercise habits, and stopping smoking).

Testing for BRCA1 and BRCA2 mutations, which are still the leading risk factors for inherited breast and ovarian cancer, has been available since the mid-1990s. But scientists now know that mutations in several other genes can increase the risk for breast and ovarian cancers; those mutations can also be detected by contemporary genetic tests.

The researchers examined data from the 2005, 2010 and 2015 National Health Interview Surveys, which are conducted by the Centers for Disease Control and Prevention. Then, drawing from the National Cancer Center Network's guidelines for managing care for people with cancer, the scientists identified five criteria to determine women for whom the genetic test would be most beneficial:

Of 47,218 women whose records were reviewed, 2.7 percent had had breast cancer. Among those who met at least one of these four criteria, 29 percent had discussed the genetic test with a health care provider, 20.2 percent were advised to undergo the test, and only 15.3 percent had taken it.

Some 0.4 percent of women in the survey had had ovarian cancer. Of them, 15.1 percent discussed the genetic test with a health care provider, 13.1 percent were advised to undergo the test and just 10.5 percent had taken it.

Based on those figures, the UCLA researchers estimated that 1.2 million to 1.3 million women in the U.S. who would be most likely to benefit from the test have not taken it.

"Many women are not receiving vital information that can aid with cancer prevention and early detection for them and their family," said co-author Kimberly Childers, a genetic counselor and regional manager of the Providence Health and Services Southern California's clinical genetics and genomics program. "Thus, we have identified an incredible unmet need for genetic testing across the country."

The paper suggests some reasons that so few women have undergone the test, including that NCCN guidelines have changed over the years, and the relatively small number of board-certified genetic counselors who specialize in cancer testing. (The researchers also note that genetic counselors are unevenly distributed throughout the country, with 500 in California but only five each in Wyoming, Alaska, Missouri and Mississippi.)

"Also, when women change doctors, their new physicians may not be aware of their histories or of the new eligibility guidelines," said James Macinko, professor of health policy and management and of community health sciences at the Fielding School, and the study's senior author.

The study has some limitations, including that data was self-reported and not verified by medical records, and that subjects may not have accurately remembered whether they discussed or took the genetic test.

Explore further: Genetic predisposition to breast cancer due to non-brca mutations in ashkenazi Jewish women

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Few women with history of breast cancer and ovarian cancer take a recommended genetic test - Medical Xpress

VIDEO Life Lessons: Next generation...

When Audrey Lapidus 10-month old son, Calvin, didnt reach normal milestones like rolling over or crawling, she knew something was wrong.

He was certainly different from our first child, said Lapidus, of Los Angeles. He had a lot of gastrointestinal issues and we were taking him to the doctor quite a bit.

Four specialists saw Calvin and batteries of tests proved inconclusive. Still, Lapidus persisted.

I was pushing for even more testing, and our geneticist at UCLA said, If you can wait one more month, were going to be launching a brand new test called exome sequencing, she said. We were lucky to be in the right place at the right time and get the information we did.

In 2012, Calvin Lapidus became the first patient to undergo exome sequencing at UCLA. He was subsequently diagnosed with a rare genetic condition known as Pitt-Hopkins Syndrome, which is most commonly characterized by developmental delays, possible breathing problems, seizures and gastrointestinal problems.

Though there is no cure for Pitt-Hopkins, finally having a diagnosis allowed Calvin to begin therapy.

The diagnosis gave us a point to move forward from, rather than just existing in that scary no-mans land where we knew nothing, Lapidus said.

Unfortunately, there are a lot of people living in that no-mans land, desperate for any type of answers to their medical conditions, said Dr. Stanley Nelson, professor of human genetics and pathology and laboratory medicine at the David Geffen School of Medicine at UCLA. Many families suffer for years without so much as a name for their condition.

What exome sequencing allows doctors to do is to analyze more than 20,000 genes at once, with one simple blood test.

In the past, genetic testing was done one gene at a time, which is time-consuming and expensive.

Rather than testing one sequential gene after another, exome sequencing saves time, money and effort, said Dr. Julian Martinez-Agosto, a pediatrician and researcher at the Resnick Neuropsychiatric Hospital at UCLA.

The exome consists of all the genomes exons, which are the coding portion of genes. Clinical exome sequencing is a test for identifying disease-causing DNA variants within the 1 percent of the genome which codes for proteins, the exons, or flanks the regions which code for proteins, called splice junctions.

To date, mutations in the protein-coding parts of genes accounts for nearly 85 percent of all mutations known to cause genetic diseases, so surveying just this portion of the genome is an efficient and powerful diagnostic tool. Exome sequencing can help detect rare disorders like spinocerebellar ataxia, which progressively diminishes a persons movements, and suggest the likelihood of more common conditions like autism spectrum disorder and epilepsy.

More than 4,000 adults and children have undergone exome testing at UCLA since 2012. Of difficult to solve cases, more than 30 percent are solved through this process, which is a dramatic improvement over prior technologies. Thus, Nelson and his team support wider use of genome-sequencing techniques and better insurance coverage, which would further benefit patients and resolve diagnostically difficult cases at much younger ages.

Since her sons diagnosis, Lapidus helped found the Pitt-Hopkins Syndrome Research Foundation. Having Calvins diagnosis gave us a roadmap of where to start, where to go and whats realistic as far as therapies and treatments, she said. None of that would have been possible without that test.

Next, experts at UCLA are testing the relative merits of broader whole genome sequencing to analyze all 6 billion bases that make up a persons genome. The team is exploring integration of this DNA sequencing with state-of-the-art RNA or gene expression analysis to improve the diagnostic rate.

The entire human genome was first sequenced in 1990 at a cost of $2.7 billion. Today, doctors can perform the same test at a tiny fraction of that cost, and believe that sequencing whole genomes of individuals could vastly improve disease diagnoses and medical care.

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Life Lessons: Next generation testing - WFMZ Allentown

In this photo provided by Oregon Health & Science University, taken through a microscope, human embryos grow in a laboratory for a few days after researchers used gene editing technology to successfully repair a heart disease-causing genetic mutation. The work, a scientific first led by researchers at Oregon Health & Science University, marks a step toward one day preventing babies from inheriting diseases that run in the family.(Oregon Health & Science University via AP)

By Johnny Kung

Mon., Aug. 21, 2017

Recently, an international team of scientists successfully corrected a disease-causing gene in human embryos, using a gene editing technique called CRISPR. This has led to much excitement about the prospects of curing debilitating diseases in entire family lineages.

At the same time, the possibility of changing embryos genes has renewed fear about designer babies. The hype in both directions should be tempered by the fact that both these scenarios are some ways off a lot more work will need to be done to improve the techniques safety and efficacy before it can be applied in the clinic.

And because a lot of diseases, as well as other physical and behavioural characteristics, are controlled by the complex interaction of many genes with each other and with the environment, in many cases simple genetic fixes may never be possible.

But while the technology is still in early stages, now is the time to have frank, open and societywide conversations about how gene editing should be moving forward and genetic medicine more broadly, including the use of advanced genetic testing and sequencing to diagnose disease, personalize medical treatments, screening babies, etc.

We must raise broad awareness of the health benefits as well as the personal, social and ethical implications of genetics. This is important for individuals both to understand their options when making decisions about their own health care, and to participate as informed citizens in democratic deliberations about whether and how genetic technologies should be developed and applied.

In the U.S., affordability and insurance coverage strongly influence access to genetic medicine. In Canada, the reality of strapped budgets means access is far from equal either. But our public health-care system means it is at least conceivable that these technologies will eventually be available to a higher proportion of people who need them.

For example, OHIP currently pays for genetic testing and counselling for a number of diseases, such as http://www.mountsinai.on.ca/care/mkbc/medical-services/genetic-testingBRCA testingEND for breast and ovarian cancer, for patients who satisfy certain eligibility criteria. It also covers a kind of genetic screening tests called non-invasive prenatal testing (NIPT) for eligible pregnant women. Precisely because of this potential for widespread adoption, there is all the greater need for broad-based conversations about genetics.

Crucially, to ensure that the largest possible cross section of society will benefit from, and not be harmed by, advances in genetic technologies, these conversations must include the voices of all communities.

This is especially true for those who, for well-justified historical reasons, may harbour deep distrust of the biomedical establishment. In the U.S., for much of the 20th century, the eugenics movement had resulted in a range of sterilization programs, discriminatory policies and scientific abuses (such as the infamous Tuskegee syphilis trials) that disproportionately targeted the poor and, especially, racial minorities such as African Americans.

While the eugenics movement might have been less established in Canada, where it did occur (e.g., the sterilization program in Alberta or the Indian hospitals in B.C.) it had most heavily affected Indigenous communities. In both countries, this shameful history has led to lower trust and usage of the health-care system by the affected communities.

As genetic medicine advances, many scientists and health researchers are pointing out the importance of having the diversity of human populations represented in genetic studies in order to gain medical insights that can benefit everyone. If we fail to fully engage these under-represented communities and ensure that genetics is not just another way to exploit and discriminate against them, then we risk worsening this historical and ongoing injustice.

New genetic technologies, such as gene editing, also bring issues of disability rights into sharper focus. While designer babies may not be an immediate concern, even the possibility of selecting and changing our offsprings characteristics raises thorny questions.

For example, what conditions count as medically necessarily to treat how about deafness, dwarfism, autism, or intersex conditions? Ultimately, it is about what kinds of people get to live, and who gets to make those decisions. Many disability rights advocates (e.g., the Down syndrome community) are already voicing concerns about what these emerging technologies mean for how their communities are seen and valued today.

We must make sure that the conversations around genetics are not only about generalized notions of safety or effectiveness, or concerns of playing God. These conversations must also encompass questions of access and justice, and acknowledge that the benefits and harms of genetic technologies, like any new technologies, are not distributed equally.

And these conversations must involve all communities (be they of different racial or ethnic background, gender or sexuality, and physical or cognitive abilities) in a way that ensures their voices are respected and heard.

This is a task that will involve concerted efforts from scientists, funders and industry, to build trust with these communities and to genuinely listen and respond to their concerns. And it will need to be done in collaboration with many partners, including schools, community and faith groups, and the art/entertainment industry.

The ability to understand and, perhaps one day, change our genetics has huge potential to improve human well-being. Lets make sure that everyone will enjoy these benefits, and that no communities are left behind, or worse yet, harmed in the process.

Johnny Kung is the director of new initiatives for the Personal Genetics Education Project (www.pged.org ) at Harvard Medical Schools Department of Genetics.

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Designer babies the not most urgent concern of genetic medicine - Toronto Star

We all have about 24,000 genes. How those genes are structured and interact can determine our current health and our future health.

Modern medicine includes specialists in this field called Clinical Geneticists. In todays TPR Lifeline, Bioscience-Medicine reporter Wendy Rigby talks to Baylor College of Medicines Scott McLean, MD, about his work at the Childrens Hospital of San Antonio.

Rigby: Dr. McLean, what is clinical genetics?

McLean: Clinical genetics is the medical specialty that uses genetic information to improve your genetic health or to understand the basis for a variety of medical conditions.

Those of us who have had children in Texas know that while youre still in the hospital, you get some genetic testing done. What is that called and what are you looking for?

We have newborn screening which is actually a blood test that is given to all babies 24 and 48 hours of age. The blood test involves collecting that blood on a piece of paper, filter paper, and sending that to the Texas State Department of Health Services in Austin where they do a series of tests.

This is the foot prick?

This is where you prick the heel. It seem awfully cruel. Babies cry. Parents dont like it. But its actually a wonderful test because it allows us to screen for over 50 conditions.

Give us some examples. What are some of the genetic conditions we might have heard of?

Well, the initial condition that was screened for in newborn screening in the United States was PKU which stands for Phenylketonuria. This is a condition that results in intellectual disability and seizures. We can change that outcome if we are able to identify the condition early enough and change the diet.

Lets say a child comes in to Childrens Hospital of San Antonio. Doctors are having trouble figuring out whats going on. Are you called in to consult?

Most of our patients that we see in the outpatient clinic are sent to us by consultation from physicians in the community or from nurseries, neonatal intensive care units. They range from situations such as multiple birth defects, to autism, intellectual disability, seizures, encephalopathy, blindness, deafness. Theres a whole gamut of reasons that folks come to see us.

When these children become grownups, does that information that youve learned about them help them out if theyre planning to have their own children in the future?

So when pediatric patients make the transition from pediatric care to adult care, its very common for information and ideas to get lost. And we certainly would hope that people remember that. Sometimes when we have identified a situation in a little baby, I tell the parents that I want them to put a sticky note on the last page of their baby book so that when they are showing the baby book to their childs fiance and they get to the last page, it reminds them you need to go back to see the geneticist because theres this genetic situation that you need to have a nice long chat about so that you can plan your family as carefully as possible.

Right. So the work youre doing today could help someone 30 years in the future.

Well, genetics is a very unique specialty in that regard because when we see a patient were not thinking about their next year of life or their next two years of life or the next month. We do think about that. But this is a lifelong diagnosis and a lifelong situation. So I often joke with my patients that Im going to try to put them on the 90-year plan. What we figure out now about their genetics is going to be helpful for them throughout their entire lifespan, at least up until 90 years. And then after that theyre on their own. But well get them to 90.

So its an exciting time to be in the field.

Very exciting. I think the era of gene therapy which for many people we thought was never going to happen, its very promising because we have new technologies that I think are going to allow for advances in that area.

Dr. Scott McLean with Baylor College of Medicine and the Childrens Hospital of San Antonio, thanks for the information.

Youre quite welcome.

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TPR Lifeline: Clinical Genetics Is A Growing Field - Texas Public Radio

Credit: CC0 Public Domain

A comprehensive genomic analysis of Wilms tumor - the most common kidney cancer in children - found genetic mutations involving a large number of genes that fall into two major categories. These categories involve cellular processes that occur early in kidney development. The study, published in Nature Genetics, offers the possibility that targeting these processes, instead of single genes, may provide new opportunities for treatment of Wilms tumor.

"It is very difficult to therapeutically target over 40 genes that may be mutated in Wilms tumor," said senior author Elizabeth Perlman, MD, from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago. "We discovered that many of these genetic mutations converge into two developmental pathways that lead to cancer. Early development of the kidney starts with rapid proliferation of undifferentiated cells. Within these cells, a signal triggers a switch to undergo differentiation into the normal cells of the kidney. In Wilms tumors, one set of mutations promotes abnormal and continued proliferation of the undifferentiated cells. A second set of mutations impacts the differentiation switch itself. Targeting these two different pathways in future studies might be more efficient than targeting individual gene mutations."

Perlman is the Head of the Department of Pathology and Laboratory Medicine at Lurie Children's and a Professor of Pathology at Northwestern University Feinberg School of Medicine. She is the Arthur C. King Professor of Pathology and Laboratory Medicine.

In the study, Perlman and colleagues in the Children's Oncology Group and the National Cancer Institute initially identified all genetic mutations in 117 Wilms tumor cases. Then they focused on a set of genetic mutations that occurred in more than one case and conducted a targeted analysis of these recurrent mutations in 651 Wilms tumors to validate the results. They found that the most common genes mutated in Wilms tumor were TP53, CTNNB1, DROSHA, WT1 and FAM123B.

In an unexpected finding, Perlman and colleagues also identified underlying germline mutations - or mutations in all the cells of the body - in at least 10 percent of Wilms tumor cases. "Our discovery of germline mutations in so many cases of Wilms tumor means that the children and family members of these patients may be at risk for tumor development," said Perlman.

Explore further: Researchers find new gene mutations for Wilms Tumor

More information: A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nature Genetics (2017). DOI: 10.1038/ng.3940

Journal reference: Nature Genetics

Provided by: Ann & Robert H. Lurie Children's Hospital of Chicago

Read more here:
Comprehensive genomic analysis offers insights into causes of Wilms tumor development - Medical Xpress

Mathias Uhlen

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.Center for Biosustainability, Danish Technical University, Copenhagen, Denmark.School of Biotechnology, AlbaNova University Center, KTHRoyal Institute of Technology, Stockholm, Sweden.

Cheng Zhang

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Sunjae Lee

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Evelina Sjstedt

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Linn Fagerberg

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Gholamreza Bidkhori

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Rui Benfeitas

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Muhammad Arif

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Zhengtao Liu

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Fredrik Edfors

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Kemal Sanli

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Kalle von Feilitzen

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Per Oksvold

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Emma Lundberg

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Sophia Hober

School of Biotechnology, AlbaNova University Center, KTHRoyal Institute of Technology, Stockholm, Sweden.

Peter Nilsson

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Johanna Mattsson

Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Jochen M. Schwenk

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.

Hans Brunnstrm

Division of Pathology, Lund University, Skne University Hospital, Lund, Sweden.

Bengt Glimelius

Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Tobias Sjblom

Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Per-Henrik Edqvist

Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Dijana Djureinovic

Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Patrick Micke

Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Cecilia Lindskog

Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Adil Mardinoglu

Science for Life Laboratory, KTHRoyal Institute of Technology, Stockholm, Sweden.School of Biotechnology, AlbaNova University Center, KTHRoyal Institute of Technology, Stockholm, Sweden.Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.

Fredrik Ponten

Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.

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A pathology atlas of the human cancer transcriptome - Science Magazine

Using fragments of circulating tumor DNA in blood, University of California San Diego School of Medicine researchers were able to identify theoretically targetable genetic alterations in 66 percent of patients with cancer of unknown primary (CUP), a rare disease with seven to 12 cases per 100,000 people each year.

In order to plan treatment for cancer in general, physicians first attempt to pinpoint the primary cancer where the tumor first developed. In CUP, despite its spread throughout the body, the origin remains unknown, making treatment more difficult. The current standard of care is platinum-based combination chemotherapies with a median survival time of six to eight months.

Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at Moores Cancer Center at UC San Diego Health.

In a study published in the journal Cancer Research on August 15, researchers report that by sequencing circulating tumor DNA (ctDNA) derived from blood samples in 442 patients with CUP, they were able to identify at least one genetic alteration linked to cancer in 290 66 percent of patients. Researchers used a screening test developed by Guardant Health that evaluates up to 70 genes. Based on known carcinogenic mutations, 99.7 percent of the 290 patients who had detectable tumor DNA in their bloodstream had genomic alterations that could hypothetically be targeted using existing FDA-approved drugs (as off-label use) or with therapies currently under investigation in clinical trials.

By definition, CUP does not have a definite anatomical diagnosis, but we believe genomics is the diagnosis, said Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at Moores Cancer Center at UC San Diego Health and senior author. Cancer is not simple and CUP makes finding the right therapy even more difficult. There are multiple genes and abnormalities involved in different areas of the body. Our research is the first to show that evaluating circulating tumor DNA from a tube of blood is possible in patients with CUP and that most patients harbor unique and targetable alterations.

A blood or liquid biopsy is a diagnostic tool based on the idea that critical genetic information about the state of disease can be found in blood or other fluids. One vial of blood could be used to detect the onset of disease, monitor its progression and measure its retreat less invasively than a tissue biopsy.

Shumei Kato, MD, assistant professor of medicine at UC San Diego School of Medicine.

Another advantage of the liquid biopsy is that the location of the cancer does not matter, said Shumei Kato, MD, assistant professor of medicine at UC San Diego School of Medicine and first author. With a blood sample, we can analyze the DNA of tumors throughout the body to find targetable alterations. With tissue biopsies, we can only see genomic changes that are in that one site and that may not be the same as what is in different sites not biopsied, such as the lung or bone.

Liquid biopsies are relatively simple to get and can be obtained regularly to monitor changes over time, as was the case with a 60-year-old woman with CUP. Her case, which was evaluated by Brian Leyland-Jones, MB, BS, PhD and study co-author with colleagues at Avera Cancer Institute, was described in the study to show the changes observed in ctDNA over the course of her treatment.

What we saw was that the patient was responding to treatment, but the cancer had emerging new mutations, said Kurzrock. Whats new here is that we can do the same evaluation through a blood test that we previously could only do with a tissue sample. You will see these changes with a simple blood test and it is easy to repeat blood tests, but hard to repeat tissue biopsies.

The study also reported the case of an 82-year-old man who was prescribed a checkpoint inhibitor immunotherapy as part of his treatment because of a mismatch repair gene anomaly that is typically observed in less than two percent of patients. He showed a partial response within eight weeks and blood biopsies showed the tumor DNA disappearing.

We can see that each patient has different mutations in their tumor DNA, which means that treatment plans cannot be a one-size-fits-all approach; a personalized approach is needed, said Kato.

Kurzrock is already using liquid biopsy technology in the Profile Related Evidence Determining Individualized Cancer Therapy (PREDICT) clinical trial a project focusing on the outcome of patients who have genomic testing performed on their tumors and are treated with targeted therapy.

The authors suggest that a liquid biopsy approach should be further investigated in next-generation clinical trials focusing on CUP.

Co-authors include: Nithya Krishnamurthy, Scott M. Lippman, UC San Diego; Kimberly C. Banks, Richard B. Lanman, Guardant Health, Inc.; Pradip De, Kirstin Williams, and Casey Williams, Avera Cancer Institute.

This research was funded, in part, by the National Cancer Institute (P30 CA016672) and the Joan and Irwin Jacobs fund.

Disclosure: Razelle Kurzrock receives consultant fees from X-biotech and from Actuate Therapeutics, as well as research funds from Genentech, Pfizer, Sequenom, Guardant, Foundation Medicine and Merck Serono, and has an ownership interest in Novena Inc. and CureMatch Inc.

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Blood Biopsy Reveals Unique, Targetable Genetic Alterations in Patients with Rare Cancer - UC San Diego Health

Researchers from Portland, Ore. genetically modified human embryos for the first time on American soil, but this is not a new feat. The process has already been done in China. To date, no genetically modified embryo has been inserted into a womb.

The lead researcher, Shoukhrat Mitalipov of Oregon Health and Science University, has a history of embryo work and demonstrated this round that its possible to safely remove inherited diseases by changing defective genes. This is called germline engineering. However, none of the embryos were allowed to last longer than a few days and the results are still pending publication.

Germline engineering typically uses CRISPR-Cas9, technology which precisely alters DNA. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats.

At its roots, CRISPR is comprised of a small piece of RNA and a protein called Cas9. The RNA is preprogrammed to match a specific genetic code to then subsequently alter a specific strand of DNA once injected. The RNA guides the injection, and Cas9 tags along because, as an enzyme, it is able to break the DNA at an exact spot.

The challenge is that DNA tends to repair itself pretty fast. To avoid this, some CRISPR injections carry another strand of DNA the cell can use to fix the break thats created, therefore allowing genetic alterations.

The implications are very large, Dr. Charles Murry, Director of the UW Medicines Institute for Stem Cell and Regenerative Medicine, said. It gives us the ability to permanently eradicate a genetic disease from a familys pedigree. And as a physician, thats something thats extremely exciting to me.

Genetic modifications have been around for decades, and CRISPR has applied since early 2013. The possibilities for CRISPR were first realized through a natural bacterial process that defends against invasive viruses also known as this all started with yogurt, surprise.

However, the real breakthrough happened in 2015 with Junjiu Huangs first human embryo edits in China. Scientists are also looking at this system to eliminate pests and the diseases they carry.

Theres another side to it of course, Murry contended. When humans begin to rewrite our own genetic code, and there are all kinds of chances to not only make corrections as we edit but to make new mistakes as we edit we may inadvertently create problems in the attempt to solve others.

UW Health Sciences and Medicine public information editor Leila Gray said UW Medicine researchers are using CRISPR on specific somatic cells, which are the ones that make up your body. These cells were collected from patients with their approval. One team, for example, is trying to edit cells with kidney disease, studying certain conditions in petri dishes. But no UW researcher is reporting work to remove genetic diseases from human embryos.

Currently, the National Institutes of Health wont federally fund this research. However, the National Academy of Sciences and the National Academy of Medicine are recommending cautious reconsideration.

Murry predicts that before any of this would apply to a human being, a large animal would have to successfully carry to term a genetically modified embryo. Scientists would also likely have to monitor the newborns life afterward.

There are ethical conundrums with this new technology. Its so concerning that upon its first big embryonic debut, there was a three-day summit in December 2015 for hundreds of local and global scientists, policymakers, and the US presidential science adviser.

Some worry genetic engineering could lead to a dark future where humans are pre-edited for appearance, physical strength, or intelligence.

George Church, a Harvard Medical School geneticist, first told the Washington Post two years ago that there were nearly 2,000 genetic therapy trials already underway that didnt use CRISPR. The difference between those and the few that have is cost.

Its about 1,000 times cheaper for an ordinary academic to do, Church is quoted in the article. It could be a game-changer.

Reach reporter Kelsey Hamlin at news@dailyuw.com. Twitter: @ItsKelseyHamlin

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First human embryo genetically modified in the US - Dailyuw

James N. Jarvis, MD, is conducting a study of the gene-environment paradigm for juvenile idiopathic arthritis pathogenesis.

Published August 14, 2017

JamesN. Jarvis, MD, clinical professor of pediatrics, will usean Arthritis Foundationgrant to study how genes and environment work together to influencethe immune dysfunction in juvenile arthritis.

After asthma, juvenile idiopathic arthritis (JIA) is the mostcommon chronic disease condition in children. While genetics play asmall role in the disease, environmental factors are also known tobe important.

Study Focuses on Influence of Epigenome

The study, titled Interplay Between Genetics andEpigenetics in Polyarticular JIA, builds upon previous workby Jarvis and his fellow researchers.

The epigenome refers to the features of DNA and the proteinsthat DNA is wrapped around that do not control the genetic makeupof a person but do influence how cells respond to the environment,says Jarvis, principal investigator on the grant.

Specifically, the epigenome determines what genes a cellwill turn on or turn off in response to environmental cues,he notes.

New Paradigm of Pathogenesis Informs Research

Like most complex traits, genetic risk for JIA is principallylocated within non-coding regions of the genome.

Our preliminary studies present the hope that we canfinally understand the gene-environment paradigm forJIA pathogenesis, Jarvis says.

Rather than regarding JIA as an autoimmunedisease, triggered by inappropriate recognition of aself protein by the adaptive immune system, Jarvishypothesizes that JIA emerges because leukocytes suffer geneticallyand epigenetically mediated perturbations that blunt their capacityto regulate and coordinate transcriptions across the genome.

This loss of coordinate regulation leads to inappropriateexpression of inflammatory mediators in the absence of the normalexternal signals typically required to initiate or sustain aninflammatory response, he says.

Our field has been dominated by a single hypothesis forJIA pathogenesis for 30 years, Jarvis notes. However,as the field of functional genomics becomes increasingly wedded tothe field of therapeutics, our work carries the promise ofcompletely new approaches to therapy based on a completelydifferent paradigm of pathogenesis.

Newly Diagnosed Children Tested in Study

The researchers are recruiting 30 children with newly diagnosedpolyarticular JIA for its study to survey the epigenome and CD4+ Tcells in them and compare the results with findings in 30 healthychildren.

We plan to build a multidimensional genomic map thatsurveys the functional epigenome, examines underlying geneticvariation and examines the effects of genetic and epigeneticvariation on gene expression, Jarvis says.

He notes the work will focus on CD4+ T cells because theresearchers have already identified interesting interactionsbetween their epigenome and transcriptome in the context oftherapeutic response in JIA.

Taking Novel Approach to Understanding Disease

Because the epigenome is the medium through which theenvironment exerts its effects on cells, Jarvis believes thatcharacterizing the epigenome in pathologically relevant cells,ascertaining where epigenetic change is linked to genetic variationand determining how genetic and epigenetic features of the genomeregulate or alter transcription is the key to truly understandingthis disease.

This project addresses a question that parents alwaysask, which I never thought wed begin to answer in mylifetime: What causes JIA? This study wontprovide the whole answer, but it will go a long way toward takingus there, he says.

The project has three specific aims:

Arthritis Patients Help Determine Funded Projects

The two-year, $730,998 grant is part of the ArthritisFoundations 2016 Delivering on Discovery awards. It was oneof only six projects out of 159 proposals chosen for funding. Forthe first time, arthritis patients helped the foundation selectprojects.

Including patient input as part of the selection processwas a new milestone in patient engagement for the ArthritisFoundation and allowed us to select projects that hold the mostpromise from an arthritis patients point of view,says Guy Eakin, senior vice president, scientific strategy.

Partners from JSMBS, Philadelphia Hospital

Collaborators from the JacobsSchool of Medicine and Biomedical Sciences are:

Other collaborators include researchers from theChildrens Hospital of Philadelphia.

See the article here:
Studying How Genes, Environment Contribute to Juvenile Arthritis - UB School of Medicine and Biomedical Sciences News

By KIMBERLY HOUGHTONUnion Leader CorrespondentAugust 14. 2017 11:06PM

This sequence of images shows the development of embryos after being injected with a biological kit to edit their DNA, removing a genetic mutation known to cause hypertrophic cardiomyopathy.(Oregon Health & Science University)

Bryan Luikart, an associate professor of molecular and systems biology at Geisel School of Medicine at Dartmouth College.

It is pretty amazing. It is a super-exciting time to be a scientist right now, said Bryan Luikart, an associate professor of molecular and systems biology at Geisel School of Medicine at Dartmouth College.

The study, which was published in the journal Nature, was detailed in a New York Times report. According to the article, Oregon researchers reported they repaired dozens of human embryos, fixing a mutation that causes a common heart condition that can lead to sudden death later in life.

The way they have dodged some ethical considerations is that they didnt go on to have that embryo grow into a person, said Luikart, explaining that if the embryos with the repaired mutation did have the opportunity to develop, they would be free of the heart condition.

At the Geisel School of Medicine at Dartmouth, Luikart and his colleagues have already been using this concept with mouse embryos, focusing specifically on autism.

Researchers are using the gene-editing method called CRISPR-Cas9 in hopes of trying to more fully understand autism, which he said is the most critical step in eventually finding a cure.

I think the CRISPR is a tremendous breakthrough. The question really is where and when do you want to use it, Luikart said. I have no ethical concerns using it as a tool to better understand biology.

The new milestone, an example of human genetic engineering, does carry ethical concerns that Luikart said will trigger some debates. He acknowledged that while the advancement of gene-editing technology could eventually stop unwanted hereditary conditions, it also allows for creating babies with smarter, stronger or more attractive traits.

The ability to do that is now within our grasp more than it has ever been, he said.

More importantly, the breakthrough could ultimately eliminate diseases, Luikart said. As the technology advances, he said, genetic diseases that are passed down to children may be corrected before the child receives them.

He used another example of a brain tumor, which often returns after it is surgically removed. Now, once the brain tumor is removed, there is the possibility of placing something in the space to edit and fix the mutation that causes the brain tumor in the first place if physicians are able to find the right cell to edit, Luikart said.

People are definitely thinking along those lines, or cutting the HIV genome, said Luikart, who predicts that those advancements will occur in mice within the next decade, and the ability to do that in humans is definitely there.

The big question is whether that can occur without some sort of side effect that was not predicted, he said.

Columbia University Medical Center posted an article earlier this year warning that CRISPR gene editing can cause hundreds of unintended mutations, based on a study published recently in Nature Methods.

This past May, MilliporeSigma announced it has developed a new genome editing tool that makes CRISPR more efficient, flexible and specific, giving researchers more experimental options and faster results that can accelerate drug development and access to new therapies, according to a release.

CRISPR genome editing technology is advancing treatment options for some of the toughest medical conditions faced today, including chronic illnesses and cancers for which there are limited or no treatment options, states the release, adding the applications of CRISPR are far ranging from identifying genes associated with cancer to reversing mutations that cause blindness.

It is pretty big news, Luikart said.

khoughton@newstote.com

HealthHanover

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New Hampshire biologist reacts to gene-editing discovery - The Union Leader

FAIRBANKS Organizers hope a giant fundraiser Saturday will help save the life of a baby.

Six-month-old Quinn Bartholomew has been diagnosed with spinal muscular atrophy (SMA), the No. 1 genetic cause of death ininfants. She is the daughter of lifelong Fairbanksan Brienna Marok-Bartholomew and Jack Bartholomew.

A new drug called Spinraza recently wasapproved by the Federal Drug Administration to combat the condition, but the drug is very expensive. Little Quinn will need at least seven treatments at a cost of $125,000 per dose.

Her insurance will not cover the medication or any expenses pertaining to the procedure, fundraiser organizers said. This means insurance will not pay for the medicine, hospital stay, anesthesia, bloodwork, radiology and more.

So family and friends are reaching out to Fairbanksans for help.

Fairbanksans are responding, as always, with incredible generosity. People can donate and also keep track of Quinns progress on YouCaring.com at http://bit.ly/2wKUOFK. The posts are heart rending.

Spinal muscular atrophy is a genetic disease in which the motor neurons in the spinal cord degenerate, causing muscle weakness. Babies born with Type 1, like Quinn, are very floppy and have trouble swallowing and feeding. Life expectancy is generally less than two years.

The good news is, it appears Quinn is benefitting from the treatments. Her parents posted on the YouCaring site Saturday: We are only two treatments in and already we have seen drastic improvements, not only in Quinns strength, but her personality as well. She has been able to hold her head up for around five seconds on multiple occasions over the last few days. She wakes us up every morning with giggles and gurgling stories.

Her third treatment is Wednesday.

When friends of the family offered to organize fundraisers to help pay for these treatments, the Maroks and Bartholomews were grateful. Now, they are overwhelmed at the outpouring of love and support.

Quinns grandparents are retired teachers Bob and Blanche Marok. They have lived in Alaska for 40 years and in Fairbanks for the past 28 years. They are longtime volunteers in the community for everything from Fairbanks Community Food Bank and hospice to sports activities and youth organizations. Over the years, they served as foster parents for 26 children through Fairbanks Counseling and Adoption. Their three children, Chris, Brienna and Trina, all grew up in Fairbanks.

The generosity of the community has been overwhelming, Bob Maroksaid.

People are always asking us, Why do you live in Fairbanks? he said. This is exactly why. Its just blown us away.

The big fundraiser planned for Saturday is called Quinns Roundup. Everyone is invited to saddle up for an evening of games, raffles and shopping, as everyone rounds up funds for Quinns treatments.

The fundraiser takes place at the Event Center and Lounge, 1288 Sadler Way. Doors open at 2 p.m. The silent auction is 2-7 p.m. and a taco bar opens at 5 p.m. An outcry auction begins at 8 p.m. There will be live music throughout the day, including a performance by Nashville singer Ryan Bexley. The fundraiser will include outside volleyball, vendors, 50/50 raffle and door prizes. Some of the auction items aregift cards, artwork, tickets to NASCARevents, airline tickets, a Hawaiian vacation package, chainsaw, the chance to have a photo booth at your own event, hotel stays and gift baskets.

All proceeds go to Quinn and her family to help pay for medical treatments.

Organizers are recruiting support from vendors, donations of gift certificates, merchandise or services. Contact Krystal Wester at 750-6098 or drop off auction donations at the Chris Marok Allstate Agency, 59 College Road.

Another fundraiser is set for Aug. 25. From 5:30-8:30 p.m., you can Spin for Quinn at Lavelles Taphouse. F&H Fitnessis hosting the event. Its a Spin-athon that includes a live disc jockey, prizes and refreshments.

Reach columnist/community editor Kris Capps at kcapps@newsminer.com. Call her at the office: 459-7546. Follow her on Twitter: @FDNMKris.

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Fairbanks fundraiser benefits baby with genetic disease - Fairbanks Daily News-Miner

Using health insurance claims data from more than 480,000 people in nearly 130,000 families, researchers have created a new classification of common diseases based on how often they occur among genetically-related individuals.

Researchers hope the work, published this week in Nature Genetics, will help physicians make better diagnoses and treat root causes instead of symptoms.

Understanding genetic similarities between diseases may mean that drugs that are effective for one disease may be effective for another one, says senior author Andrey Rzhetsky, professor of medicine and human genetics at the University of Chicago. And for those diseases with a large environmental component, that means we can perhaps prevent them by changing the environment.

The results of the study suggest that standard disease classificationscalled nosologiesbased on symptoms or anatomy may miss connections between diseases with the same underlying causes. For example, the new study showed that migraine, typically classified as a disease of the central nervous system, appeared to be most genetically similar to irritable bowel syndrome, an inflammatory disorder of the intestine.

Rzhetsky and a team of researchers analyzed records from Truven MarketScan, a database of de-identified patient data from more than 40 million families in the United States. They selected a subset of records based on how long parents and their children were covered under the same insurance plan within a time frame most likely to capture when children were living in the same home with their parents. They used this massive data set to estimate genetic and environmental correlations between diseases.

Next, using statistical methods developed to create evolutionary trees of organisms, the team created a disease classification based on two measures. One focused on shared genetic correlations of diseases, or how often diseases occurred among genetically-related individuals, such as parents and children. The other focused on the familial environment, or how often diseases occurred among those sharing a home but who had no or partially matching genetic backgrounds, such as spouses and siblings.

The results focused on 29 diseases that were well represented in both children and parents to build new classification trees. Each branch of the tree is built with pairs of diseases that are highly correlated with each other, meaning they occur frequently together, either between parents and children sharing the same genes, or family members sharing the same living environment.

The large number of families in this study allowed us to obtain precise estimates of genetic and environmental correlations, representing the common causes of multiple different diseases, says Kanix Wang, a graduate student and lead author of the study. Using these shared genetic and environmental causes, we created a new system to classify diseases based on their intrinsic biology.

Genetic similarities between diseases tended to be stronger than their corresponding environmental correlations. For the majority of neuropsychiatric diseases, such as schizophrenia, bipolar disorder, and substance abuse, however, environmental correlations are nearly as strong as genetic ones. This suggests there are elements of the shared, family environment that could be changed to help prevent these disorders.

The researchers also compared their results to the widely used International Classification of Diseases Version 9 (ICD-9) and found additional, unexpected groupings of diseases. For example, type 1 diabetes, an autoimmune endocrine disease, has a high genetic correlation with hypertension, a disease of the circulatory system. The researchers also saw high genetic correlations across common, apparently dissimilar diseases such as asthma, allergic rhinitis, osteoarthritis, and dermatitis.

The study received support from the Defense Advanced Research Projects Agency (DARPA) Big Mechanism program, the National Institutes of Health, and a gift from Liz and Kent Dauten. Additional authors are from the University of Chicago, Microsoft Research, and Vanderbilt University.

Source: University of Chicago

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Insurance claims reveal new links among diseases - Futurity: Research News

On August 2nd, scientists achieved a milestone on the path to human genetic engineering. For the first time in the United States, scientists successfully edited the genes of a human embryo. A transpacific team of researchers used CRISPR-Cas9 to correct a mutation that leads to an often devastating heart condition. Responses to this feat followed well-trodden trails. Hype over designer babies. Hope over new tools to cure and curb disease. Some spin, some substance and a good dose of science-speak. But for me, this breakthrough is not just about science or medicine or the future of humankind. Its about faith and family, love and loss. Most of all, its about the life and memory of my brother.

Jason was born with muscle-eye-brain disease. In his case, this included muscular dystrophy, cerebral palsy, severe nearsightedness, hydrocephalus and intellectual disability. He lived past his first year thanks to marvels of modern medicine. A shunt surgery to drain excess cerebrospinal fluid building up around his brain took six attempts, but the seventh succeeded. Aside from those surgeries complications and intermittent illnesses due to a less-than-robust immune system, Jason was healthy. Healthy and happy very happy. His smile could light up a room. Yet, that didnt stop people from thinking that his disability made him worse off. My family and those in our religious community prayed for Jason. Strangers regularly came up to test their fervor. Prayer circles frequently had his name on their lists. We wanted him to be healed. But I now wonder: What, precisely, were we praying for?

Jasons disabilities fundamentally shaped his experience of the world. If praying for his healing meant praying for him to be normal, we were praying for Jason to become someone else entirely. We were praying for a paradox. If I could travel back in time, Id walk up to young, devout Joel and ask: How will Jason still be Jason if God flips a switch and makes him walk and talk and think like you? The answer to that question is hard. Yes, some just prayed for his seizures to stop. Some for his continued well-being. But is that true of most? Is that what I was praying for?

The ableist conflation of disability with disease and suffering is age-old. Just peruse the history of medicine. Decades of eugenic practices. Sanctioned torture of people with intellectual disability. The mutilation of otherwise healthy bodies in the name of functional or aesthetic normality. These stories demonstrate over and over again how easily biomedical research and practice can mask atrocity with benevolence and injustice with progress. Which leads me to ask: What, precisely, are we editing for?

Although muscle-eye-brain disease does not result from a single genetic variant, researchers agree that a single gene, named POMGNT1, plays a large role. Perhaps scientists will soon find a way to correct mutations in that and related genes. Perhaps people will no longer be born with it. But that means there would never be someone like Jason. Those prayers I mentioned above? Science will have retroactively answered them. That thought brings me to tears.

I wish we could cure cancer, relieve undue pain and heal each break and bruise. But I also wish for a world with Jason and people like him in it. I want a world accessible and habitable for people full stop not just the people we design. I worry that in our haste to make people healthy, we are in fact making people we want. We, who say we pray for healing, but in fact pray for others to be like us. We, who say were for reducing disease and promoting health, but support policies and practices aimed instead at being normal. We, who are often still unable to distinguish between positive, world-creating forms of disability and negative, world-destroying forms between Deafness, short stature or certain types of neurodiversity and chronic pain, Tay-Sachs or Alzheimers. It is with great responsibility that we as a society balance along the tightrope of biomedical progress. I long for us to find that balance. Ive certainly not found it for myself. Lest I forget how often weve lost it and how easy it is to fall, I hold dearly onto the living memory of Jason. I no longer pray for paradoxes, but for parity for the promise of a world engineered not for normality, but equality.

But that world will never come if we edit it away.

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Gene Editing Might Mean My Brother Would've Never Existed - TIME

CHARLOTTESVILLE, Va. (WVIR) -

The University of Virginia School of Medicine is using a $50,000 donation to further research for an un-named, rare genetic disorder.

The money comes from the Bow Foundation which works to help people affected by the disease. Right now the disease is fairly new; it was only discovered in the past year and has only 50 known patients.

The disorder has mainly been targeting children, and can cause seizures, severe development delays, and movement disorders.

"By making the cells that we're making from the first patients, we'll then be able to compare those cells with other researchers and really broaden the research in this field. In a way that wouldn't be possible without this initial funding, Mike McConnell, UVA professor and researcher, said.

The hospital says they still know very little about this disease, but the funding is a step in the right direction.

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UVA School of Medicine Using Grant to Research Rare Genetic Disorder - NBC 29 News

The chip has not been tested in humans, but it has been used to heal wounds in mice. Wexner Medical Center/The Ohio State University hide caption

The chip has not been tested in humans, but it has been used to heal wounds in mice.

Scientists have created an electronic wafer that reprogrammed damaged skin cells on a mouse's leg to grow new blood vessels and help a wound heal.

One day, creator Chandan Sen hopes, it could be used to be used to treat wounds on humans. But that day is a long way off as are many other regeneration technologies in the works. Like Sen, some scientists have begun trying to directly reprogram one cell type into another for healing, while others are attempting to build organs or tissues from stem cells and organ-shaped scaffolding.

But other scientists have greeted Sen's mouse experiment, published in Nature Nanotechnology on Monday, with extreme skepticism. "My impression is that there's a lot of hyperbole here," says Sean Morrison, a stem cell researcher at the University of Texas Southwestern Medical Center. "The idea you can [reprogram] a limited number of cells in the skin and improve blood flow to an entire limb I think it's a pretty fantastic claim. I find it hard to believe."

When the device is placed on live skin and activated, it sends a small electrical pulse onto the skin cells' membrane, which opens a tiny window on the cell surface. "It's about 2 percent of the cell membrane," says Sen, who is a researcher in regenerative medicine at Ohio State University. Then, using a microscopic chute, the chip shoots new genetic code through that window and into the cell where it can begin reprogramming the cell for a new fate.

Sen says the whole process takes less than 0.1 seconds and can reprogram the cells resting underneath the device, which is about the size of a big toenail. The best part is that it's able to successfully deliver its genetic payload almost 100 percent of the time, he says. "No other gene delivery technique can deliver over 98 percent efficiency. That is our triumph."

Chandan Sen, a researcher at Ohio State University, holds a chip his lab created that has reprogrammed cells in mice. Wexner Medical Center/The Ohio State University hide caption

Chandan Sen, a researcher at Ohio State University, holds a chip his lab created that has reprogrammed cells in mice.

To test the device's healing capabilities, Sen and his colleagues took a few mice with damaged leg arteries and placed the chip on the skin near the damaged artery. That reprogrammed a centimeter or two of skin to turn into blood vessel cells. Sen says the cells that received the reprogramming genes actually started replicating the reprogramming code that the researchers originally inserted in the chip, repackaging it and sending it out to other nearby cells. And that initiated the growth of a new network of blood vessels in the leg that replaced the function of the original, damaged artery, the researchers say. "Not only did we make new cells, but those cells reorganized to make functional blood vessels that plumb with the existing vasculature and carry blood," Sen says. That was enough for the leg to fully recover. Injured mice that didn't get the chip never healed.

When the researchers used the chip on healthy legs, no new blood vessels formed. Sen says because injured mouse legs were was able to incorporate the chip's reprogramming code into the ongoing attempt to heal.

That idea hasn't quite been accepted by other researchers, however. "It's just a hand waving argument," Morrison says. "It could be true, but there's no evidence that reprogramming works differently in an injured tissue versus a non-injured tissue."

What's more, the role of exosomes, the vesicles that supposedly transmit the reprogramming command to other cells, has been contentious in medical science. "There are all manners of claims of these vesicles. It's not clear what these things are, and if it's a real biological process or if it's debris," Morrison says. "In my lab, we would want to do a lot more characterization of these exosomes before we make any claims like this."

Sen says that the theory that introduced reprogramming code from the chip or any other gene delivery method does need more work, but he isn't deterred by the criticism. "This clearly is a new conceptual development, and skepticism is understandable," he says. But he is steadfast in his confidence about the role of reprogrammed exosomes. When the researchers extracted the vesicles and injected them into skin cells in the lab, Sen says those cells converted into blood vessel cells in the petri dish. "I believe this is definitive evidence supporting that [these exosomes] may induce cell conversion."

Even if the device works as well as Sen and his colleagues hope it does, they only tested it on mice. Repairing deeper injuries, like vital organ damage, would also require inserting the chip into the body to reach the wound site. It has a long way to go before it can ever be considered for use on humans. Right now, scientists can only directly reprogram adult cells into a limited selection of other cell types like muscle, neurons and blood vessel cells. It'll be many years before scientists understand how to reprogram one cell type to become part of any of our other, many tissues.

Still, Morrison says the chip is an interesting bit of technology. "It's a cool idea, being able to release [genetic code] through nano channels," he says. "There may be applications where that's advantageous in some way in the future."

The rest is here:
A Chip That Reprograms Cells Helps Healing, At Least In Mice - NPR

JoAnne Viviano The Columbus Dispatch @JoAnneViviano

In what researchers consider a major scientific leap, a team at Ohio State University has discovered a new way of turning skin cells into any type of cells the body might need, a technology that has limitless potential, from regenerating a wounded limb to repairing a brain after stroke to healing a damaged heart.

The process involves placing a square chip about the size of a fingernail on the skin, adding a droplet containing genetic code, and zapping it with an energy source.

While it hasn't been used in humans yet, the process was used in animals to healbrains after stroke and to generate blood vessels in legs wherethe femoral artery, the limbs major blood supply, had been cut, said Chandan Sen, the director of the Center for Regenerative Medicine and Cell-Based Therapies at Ohio State's Wexner Medical Center.

In leg experiments involving mice, researchers placed the chip on the animals' wounded legs, delivered the appropriate genetic material, and saw blood vessels grown to regenerate limbs within seven to 14 days, Sen said. Legs that otherwise would have turned black and required amputation were pink, and the mice were able to run again.

In brain experiments on mice, the chip was again placed on the leg, different genetic material was dropped on, and neurological cells grew in the area. Three weeks later, scientists detected firing neurons, and the new cells were taken from the leg and inserted into the brain.

The leg-healing process was duplicated in pigs after the Walter Reed National Military Medical Center in Bethesda, Maryland, expressed interest. Sen said the technology could be used to heal troops in the field. One caveat: It must be deployed within 72 hours of a limb being damaged.

Twenty-six Ohio State researchers from the fields of engineering, science and medicine worked together to make the technology a reality.

Join the conversation at Facebook.com/columbusdispatchand connect with us on Twitter @DispatchAlerts

The discovery could have countless applications across various medical disciplines, Sen said. He's hopeful other researchers will help stretch the impact of the device.

"There are many smart minds throughout the country and the world that will take this and run," Sen said.

Sen expects that human trials will come soon, after a letter on the research is published Monday in the Nature Nanotechnology journal, a peer-reviewed scientificpublication.The research was led by Sen and L. James Lee, professor of chemical and biomolecular engineering in Ohio States College of Engineering.

Sen said it takes less than a second to deliver the genetic code that spurs the skin cells to switch to something else, then several days for new cells to grow.

The equipment needed can fit in a pocket. And the process can be done anywhere; no lab or hospital is needed.

The black chip, made of silicon, acts as a carrier for the genetic code.

"Its like a syringe thats the chip but then what you load in the syringe is your cargo," Sen explained. "Based on what you intend the cells to be, the cargo will change. So if you want a vasculogenic (blood vessel) cell, the code would be different than if you wanted a neuro cell, and so on and so forth."

The genetic code is synthetically made to mirror code from the patient.

The electric field pulls the genetic material into the skin cells.

Because the research project had a high risk of failure, and because Ohio State wanted to keep it close to the vest, public money was not sought, Sen said. Instead it was funded by university and philanthropic money from Leslie and Abigail Wexner, Ohio States Center for Regenerative Medicine and Cell-Based Therapies, and the universitys Nanoscale Science and Engineering Center.

Approval from the federal Food and Drug Administration is required before Sen, Lee and the research team can try the technique in humans. He expects to get that approval and prove human feasibility within a year. Sen's hopeful that "the floodgates will open" and then thetechnology will be used widely within five years.

The chips are already being manufactured locally due to an assist from the Rev1 Ventures business incubator on the Northwest Side, and the technology has gained interest from Taiwan-based Foxconn Technology Group.

Lee called the concept very simple and said he was surprised by how well it worked.

He had developed similar technology prior to 2011, but it only worked on individual cells and only in processes separate from the body. Since then, he said, many researchers and companies have approached him to come up with a system that worked on tissue in the body.

"More and more people said, 'This technology can be very, very powerful if you can do tissue,'" he said. "It turns out that it works. It was very surprising."

This version, he said, is a very significant advancement and is "much, much more useful for the medical applications."

jviviano@dispatch

@JoAnneViviano

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Ohio State researchers report breakthrough in cell regeneration - The Columbus Dispatch

The ACMG Foundation for Genetic and Genomic Medicine announced Aug. 4 that Indian American Madhuri Hegde of Waltham, Mass.-based PerkinElmer Inc. was elected to its board of directors.

"We are delighted that Dr. Hegde has been elected to the ACMG Foundation Board of Directors. She has vast experience in genetic and genomic testing and is a longtime member of the college and supporter of both the college and the foundation," said Dr. Bruce R. Korf, president of the ACMG Foundation, in a statement.

Hegde, who will serve a two-year renewable term, joined PerkinElmer in 2016 as vice president and chief scientific officer of global genetics laboratory services. She is also an adjunct professor of human genetics in Emory Universitys human genetics department.

Previously, Hegde served as the executive director and chief scientific officer at Emory Genetics Laboratory in Atlanta, Ga.; professor of human genetics and pediatrics at Emory University; and assistant professor at Baylor College of Medicines Department of Human Genetics in Houston, Texas.

Additionally, Hegde has served on a number of scientific advisory boards for patient advocacy groups including Parent Project Muscular Dystrophy, Congenital Muscular Dystrophy and the Neuromuscular Disease Foundation.

She earned her doctorate from the University of Auckland in Auckland, New Zealand, and completed her postdoctoral fellowship in molecular genetics at Baylor College of Medicine. She also holds a masters from the University of Mumbai in India.

The foundation, a national nonprofit dedicated to facilitating the integration of genetics and genomics into medical practice, is the supporting educational foundation of the American College of Medical Genetics and Genomics.

Board members are active participants in serving as advocates for the foundation and for advancing its policies and programs.

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Madhuri Hegde Elected to ACMG Foundation for Genetic, Genomic ... - India West

An international team of scientists published a new study last week documenting edits theyd made to viable human embryos carrying a genetic mutation, one associated with a life-threatening heart condition. It is the first study of its kind to take place in the United States.

The researchers were able to remove a problematic mutation in the MYBPC3 gene with a higher success rate than in similar studies. After adjusting their method, 72 percent of the embryos were free of the mutation. The scientists believe they may be able to address other monogenetic diseases using the same technique, CRISPR-Cas9.

But the notion of altering human DNA to eradicate inherited diseases is generating concern, too. These genetic changes would permanently affect the DNA passed through a family line, for one. Other critics raise the possibility of altering embryos to create desired characteristics (though it would be much harder for scientists to target genes associated with humor, creativity or physical traits).

Cardiologist and geneticist Dr. Elizabeth McNally is the director of the Center for Genetic Medicine at Northwestern University. She joins Phil Ponce in discussion.

Related stories:

UIC Launches Stem Cell, Regenerative Medicine Center

June 12: Researchers at UIC will focus on understanding tissue regeneration and spearheading future developments in stem cell biology as a means to repair diseased organs and tissues.

The Science and Ethics of Editing Human Embryos

Feb. 28: Earlier this month, an influential group backs editing the genes in human embryos to eliminate disease. Chicago Tonight guests discuss human gene editing and some of the ethical issues it raises.

Baby with 3 Parents: Genetic Technique Offers Hope, Controversy

Sept. 29, 2016: A baby has been born with the DNA of three parents. We hear about the promise the technique offers for avoiding some birth defects, and the ethical concerns it raises.

Read more:
New Gene Editing Study Raises Possibilities, Questions - Chicago Tonight | WTTW

San Francisco-based genetic diagnostics company Invitae has acquired Good Start Genetics and CombiMatrix, expanding Invitaes portfolio to include prenatal and pediatric testing. Its part of their long-term plan to make genomic testing routine.

Were building a company for the coming genomic era that includes genetic capabilities through all phases of life, said Invitae CEO Sean George in a phone interview.

Invitae offers a wide range of genomic panels to detect anomalies that could contribute to heart disease, cancer, neurologic disorders and other conditions. In Good Start, Invitae picks up expertise in carrier screening and preimplantation genetic testing. CombiMatrix also provides preimplantation testing, as well as panels to analyze miscarriages and pediatric developmental disorders.

Invitae is issuing 1.65 million shares of stock, paying $18.3 million in cash and assuming $6 million in debt for privately-held Good Start. CombiMatrix shareholders will receive around $27 million in common stock.

Spun off from Genomic Health in 2012, Invitae initially focused on adult inherited diseases and has gradually expanded their portfolio. They now enter a crowded field that includes LabCorp (which acquired Sequenom last year), Illumina, Progenity and others. George believes Invitaes ability to do the hard things will carry them through these market battles.

We are building a technology engine to win the race of scale, said George. We are looking to the OB market and the perinatal space to extend our platforms capabilities. But more importantly, in order to move the world away from the current disease-by-disease, test-by-test market, its managing genetic information for an individual over the course of their life.

Good Start appealed to Invitae for their cost-effective pre-implantation screening and diagnosis. CombiMatrix brings specific expertise in chromosomal microarrays. In addition, the companies could expand Invitaes marketing reach.

The two together have a pretty good commercial presence in the IVF and reproductive medicine sector, said George. Combined, especially with our capabilities, I think its fair to say we are immediately the number one player in the IVF, reproductive medicine segment for genetic information.

These acquisitions add around 150 people to the Invitae payroll, a 20 percent workforce increase. George notes they are always looking around for potential acquisitions but will probably take a breather to focus on moving new products to market. Ultimately, Invitae wants to be the company that mainstreams clinical genomics.

With the broad capabilities we now have at all stages of life, we expect to get traction in this new age of genomic medicine, where all this information can be brought to bear, said George. The first company to have broad capabilities across all of it and to continue to lower the cost basis and deliver that information is likely in position to truly bring genetics into medicine for everybody.

Photo: mediaphotos, Getty Images

Originally posted here:
Invitae CEO says the diagnostic company has big plans for genomic medicine - MedCity News

An international team of researchers recently published, in the journal Nature, their study using genome editing to correct a heterozygous mutation in human preimplantation embryos using a technique called CRISPR-Cas9. This bench research, while far from bedside use, raises questions about the medical ethics of what could be considered genetic engineering. The AMA Code of Medical Ethics has guidance for physicians conducting research in this area.

In Opinion 7.3.6, Research in Gene Therapy and Genetic Engineering, the Code explains:

Gene therapy involves the replacement or modification of a genetic variant to restore or enhance cellular function or the improve response to nongenetic therapies. Genetic engineering involves the use of recombinant DNA techniques to introduce new characteristics or traits. In medicine, the goal of gene therapy and genetic engineering is to alleviate human suffering and disease. As with all therapies, this goal should be pursued only within the ethical traditions of the profession, which gives primacy to the welfare of the patient.

In general, genetic manipulation should be reserved for therapeutic purposes. Efforts to enhance desirable characteristics or to improve complex human traits are contrary to the ethical tradition of medicine. Because of the potential for abuse, genetic manipulation of nondisease traits or the eugenic development of offspring may never be justifiable.

Moreover, genetic manipulation can carry risks to both the individuals into whom modified genetic material is introduced and to future generations. Somatic cell gene therapy targets nongerm cells and thus does not carry risk to future generations. Germ-line therapy, in which a genetic modification is introduced into the genome of human gametes or their precursors, is intended to result in the expression of the modified gene in the recipients offspring and subsequent generations. Germ-line therapy thus may be associated with increased risk and the possibility of unpredictable and irreversible results that adversely affect the welfare of subsequent generations.

Thus, in addition to fundamental ethical requirements for the appropriate conduct of research with human participants, research in gene therapy or genetic engineering must put in place additional safeguards to vigorously protect the safety and well-being of participants and future generations.

Physicians should not engage in research involving gene therapy or genetic engineering with human participants unless the following conditions are met:

(a) Participate only in those studies for which they have relevant expertise.

(b) Ensure that voluntary consent has been obtained from each participant or from the participants legally authorized representative if the participant lacks the capacity to consent, in keeping with ethics guidance. This requires that:

(i) prospective participants receive the information they need to make well-considered decisions, including informing them about the nature of the research and potential harms involved;

(ii) physicians make all reasonable efforts to ensure that participants understand the research is not intended to benefit them individually;

(iii) physicians also make clear that the individual may refuse to participate or may withdraw from the protocol at any time.

(c) Assure themselves that the research protocol is scientifically sound and meets ethical guidelines for research with human participants. Informed consent can never be invoked to justify an unethical study design.

(d) Demonstrate the same care and concern for the well-being of research participants that they would for patients to whom they provide clinical care in a therapeutic relationship. Physician researchers should advocate for access to experimental interventions that have proven effectiveness for patients.

(e) Be mindful of conflicts of interest and assure themselves that appropriate safeguards are in place to protect the integrity of the research and the welfare of human participants.

(f) Adhere to rigorous scientific and ethical standards in conducting, supervising, and disseminating results of the research.

AMA Principles of Medical Ethics: I,II,III,V

At the 2016 AMA Interim Meeting, the AMA House of Delegates adopted policy on genome editing and its potential clinical use. In the policy, the AMA encourages continued research into the therapeutic use of genome editing and also urges continued development of consensus international principles, grounded in science and ethics, to determine permissible therapeutic applications of germline genome editing.

Chapter 7 of the Code, Opinions on Research & Innovation, also features guidance on other research-related subjects, including informed consent, conflicts of interest, use of placebo controls, and the use of DNA databanks.

The Code of Medical Ethics is updated periodically to address the changing conditions of medicine. The new edition, adopted in June 2016, is the culmination of an eight-year project to comprehensively review, update and reorganize guidance to ensure that the Code remains timely and easy to use for physicians in teaching and in practice.

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Genome editing and the AMA Code of Medical Ethics - American Medical Association (blog)