Category Archives: Gene Medicine

China and India are vying for formal recognition from UNESCO of their cultural ties to ancient Tibetan medicine. Receiving UNESCO recognition could stimulate the Tibetan medicinal industrys growth in either country, but some experts are concerned that the practices would become watered down if produced on a massive scale. (New York Times)

Simulations suggest that nearly half of the matter in the Milky Way galaxy came from the gas of other galaxies.

Visual by NurPhoto / Getty

Those who can afford to outsource tasks they dislike probably should if they want to feel happier, according to a new study in the Proceedings of the National Academy of Sciences. The study found that many people of a variety of income levels stress about not having enough time, but are reluctant to pay others to do chores and tasks for them, which the researchers report decreases well-being. (BBC)

The sperm counts in men from North America, Europe, and Australia have dropped by more than 50 percent over the course of 40 years, according to a new meta-analysis. Because low sperm count can sometimes signify other health concerns, some experts are alarmed by the finding. (Washington Post)

A group of infectious disease experts in the U.K. are making the case against completing the course of prescribed antibiotics as a way to prevent antibiotic resistance in bacteria. The groups controversial stance, which also calls on physicians to stop sending the complete the course message to patients, is receiving some pushback within the medical establishment. (Scientific American)

Using the genome-editing technique CRISPR-Cas9, biologists in Oregon have successfully edited the DNA of viable human embryos, targeting a gene connected to a major disease. Though this type of DNA editing could be used to prevent parents from passing on deadly genetic mutations to their offspring, it faces regulatory obstacles in the United States, and the embryos were not permitted to develop past an early stage. (STAT)

Scientists have discovered that Japanese tits communicate using specific sequences of sounds to alert one another of predators. But the birds only understand the sounds if they are delivered in the proper order sort of like humans only understand sentences if the words are in the right places. (Science)

Almost half of the matter present in the Milky Way might have originated in other galaxies. New simulations have found that high-speed galactic winds could have pushed atoms in gaseous forms away from their home galaxies and into other galaxies such as ours. (Science News)

The ancient Canaanites, who the Bible says were annihilated by the Israelites and who left no textual records, seemed to have survived after all. A new genetic study found that present-day Lebanese people share enough DNA with Canaanite-related populations to be considered their descendants. (Independent)

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A tumor is a trove of data.

In handling some kinds of life-or-death medical judgments, computers have already have surpassed the abilities of doctors. Were looking at something like promise of self-driving cars, according to Zak Kohane, a doctor and researcher at Harvard Medical School. On the roads, replacing drivers with computers could save thousands of lives that would otherwise be lost to human error. In medicine, replacing intuition with machine intelligence might save patients from deadly drug side effects or otherwise incurable cancers.

Consider precision medicine, which involvestailoring drugs to individual patients. And to understand its promise, look toShirley Pepke, a physicist by training who migratedinto computational biology. When she developed a deadly cancer, she responded like a scientist and fought it using big data. And she is winning. She shared her story at a recent conference organized by Kohane.

In 2013, Pepke was diagnosed with advanced ovarian cancer. She was 46, andher kids were 9 and 3. It was just two months after her annual gynecological exam. She had symptoms, which the doctors brushed off, until her bloating got so bad she insisted on an ultrasound. She was carrying six liters of fluid caused by the cancer, which had metastasized. Her doctor, she remembers, said, I guess you werent making this up.

She did what most people do in her position. She agreed to a course of chemotherapy that doctors thought would extend her life and offered a very slim chance of curing her. It was a harsh mixture pumped directly into her abdomen.

She also did something most people wouldnt know how to do -- she started looking for useful data. After all, tumors are full of data. They carry DNA with various abnormalities, some of which make them malignant or resistant to certain drugs. Armed with that information, doctors design more effective, individualized treatments. Already, breast cancers are treated differently depending on whether they have a mutation in a gene called HER2. So far, scientists have found no such genetic divisions for ovarian cancers.

But there was some data. Years earlier, scientistshad started a data bank called the Cancer Genome Atlas. There were genetic sequences on about 400 ovarian tumors. To help her extract useful information from the data, she turned to Greg ver Steeg, a professor at the University of Southern California, who was working on an automated pattern-recognition technique called correlation explanation, or CorEx. It had not been used to evaluate cancer, but she and ver Steeg thought it might work.She also got genetic sequencing done on her tumor.

In the meantime, she found out she was not one of the lucky patients cured by chemotherapy. The cancer came back after a short remission. A doctor told her that she would only feel worse every day for the short remainder of her life.

But CorEx had turned up a clue. Her tumor had something on common with those of the luckier women who responded to the chemotherapy -- an off-the-charts signal for an immune system product called cytokines. She reasoned that in those luckier patients, the immune system was helping kill the cancer, but in her case, there was something blocking it.

Eventually she concluded that her one shot at survival would be to take a drug called a checkpoint inhibitor, which is geared to break down cancer cells defenses against the immune system.

Checkpoint inhibitors are only approved so far for melanoma. Doctors can still prescribe such drugs for other uses, though insurance companies wont necessarily cover them. She ended up paying thousands of dollars out of pocket. At the same time, she went in for another round of chemotherapy. The checkpoint inhibitor destroyed her thyroid gland, she said, and the chemotherapy was damaging her kidneys. She stopped, not knowing whether her cancer was still there or not. To the surprise of her doctors, she started to get better. Her cancer became undetectable. Still healthy today, she works on ways to allow other cancer patients to benefit from big data the way she did.

Kohane, the Harvard Medical School researcher, said similar data-driven efforts might help find side effects of approved drugs. Clinical trials are often not big enough or long-running enough to pick up even deadly side effects that show up when a drug is released to millions of people. Thousands died from heart attacks associated with the painkiller Vioxx before it was taken off the market.

Last month, an analysis by another health site suggested a connection between the rheumatoid arthritis drug Actemra and heart attack deaths, though the drug had been sold to doctors and their patients without warning of any added risk of death. Kohane suspects there could be many other unnecessary deaths from drugs whose side effects didnt show up in testing.

So whats holding this technology back? Others are putting big money into big data with the aim of selling us things and influencing our votes. Why not use it to save lives?

First theres the barrier of tradition, said Kohane, whose academic specialty is bioinformatics, a combination of math, medicine and computer science. Medicine does not understand itself as an information-processing discipline, he said. It still sees itself as a combination of intuitive leaps and hard science. And doctors arent collecting the right kinds of data. Were investing in information technology thats not optimized to do anything medically interesting, he said. Its there to maximize income but not to make us better doctors.

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Physicians arent likely to be replaced by algorithms, at least not right away, but their skill sets might have to change. Already, machines have proven themselves better than humans in the ability to read scans and evaluate skin lesions. Pepke ended her talk by saying that in the future, doctors may have to think less statistically and more scientifically. Her doctors made decisions based on rote statistical information about what would benefit the average patient -- but Shirley Pepke was not the average patient. The status quo is an advance over guessing or tradition, but medicine has the potential to do so much better.

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

To contact the author of this story: Faye Flam at fflam1@bloomberg.net

To contact the editor responsible for this story: Tracy Walsh at twalsh67@bloomberg.net

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Big Data Shows Big Promise in Medicine - Bloomberg

Injectinga smaller but functional form of the dystrophin gene, called microdystrophin, intodogs naturally affected by Duchenne muscular dystrophyallowed them to recover muscle strength and stabilized their overall disease symptoms, a new study shows.

This preclinical study demonstrates the safety and efficacy of microdystrophin, and makes it possible to consider developing a clinical trial in patients, Caroline Le Guiner, first author of the study, said in a news release.

Indeed, this is the first time that it has been possible to treat the whole body of a large-sized animal with this protein. Moreover, this innovative approach allows treatment of all patients with Duchenne muscular dystrophy, regardless of the genetic mutation responsible, Le Guiner added.

The study, titled Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy, was featured in the journalNature Communications.Researchers used a delivery system based on a viral vector, a strategy commonly used in gene therapy, to inject the engineered microdystrophin in 12 Golden Retrievers naturally affected by DMD.

DMD is a rare inherited disorder caused by mutations in the gene that encodes the protein dystrophin, which is essential for normal muscle function. It is one of the longest human genes, which makes therapeutic usein its natural form technically impossible. To overcome this limitation, researchers created the new variant called microdystrophinthat is shorter, but retains the function of the protein.

The results demonstrated microdystrophins potential as a gene therapy for people with DMD. The treatment increased levels of dystrophin protein in the dogs and significantly restored muscle function. Clinical symptoms of DMD in the dogs were stabilized for more than two years following treatment. No significant adverse side effects associated with the treatment were observed, demonstrating that it can be a safe treatment strategy.

This is tremendously exciting progress towards a gene therapy for DMD, said George Dickson, senior author of the study and researcher at Royal Holloway, University of London. The studies in [Golden Retrievers naturally affected by DMD) have been spectacular and exceeded our expectations.

The study also provided important data to support the therapeutic potential of this new gene therapy for DMD in children.

This new evidence of the efficacy of gene therapy in Duchenne muscular dystrophy strengthens the therapeutic arsenal developed (exon skipping, CRISPR Cas-9, pharmacogenetics, etc.), and the first results are there. We need to forge ahead to complete the final phase and transform these scientific advances into drugs for children, said Serge Braun, scientific director of AFM-Telethon.

The study resulted from the collaborative work between researchers from Genethon, the AFM-Telethon laboratory, Inserm (Nantes), and the University of London (Royal Holloway), and was supported by donations from the French Telethon.

My team has worked for many years to optimize a gene therapy medicine for DMD, and now the quite outstanding work of colleagues in France, in Genethon, in Nantes, and in Paris has taken us close to clinical trials in DMD patients, Dickson said. I pay thanks also to the amazing and steadfast support of this research by AFM-Telethon and MDUK (Muscular Dystrophy UK) which has been essential to this achievement.

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Microdystrophin Gene Therapy Shows Promise in Dogs with Duchenne Muscular Dystrophy, Study Shows - Muscular Dystrophy News

(Reuters) - Technology that allows alteration of genes in a human embryo has been used for the first time in the United States, according to Oregon Health and Science University (OHSU) in Portland, which carried out the research.

The OHSU research is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating it is possible to safely and efficiently correct defective genes that cause inherited diseases, according to Technology Review, which first reported the news.

None of the embryos were allowed to develop for more than a few days, according to the report.

Some countries have signed a convention prohibiting the practice on concerns it could be used to create so-called designer babies.

Results of the peer-reviewed study are expected to be published soon in a scientific journal, according to OHSU spokesman Eric Robinson.

The research, led by Shoukhrat Mitalipov, head of OHSU's Center for Embryonic Cell and Gene Therapy, involves a technology known as CRISPR that has opened up new frontiers in genetic medicine because of its ability to modify genes quickly and efficiently.

CRISPR works as a type of molecular scissors that can selectively trim away unwanted parts of the genome, and replace it with new stretches of DNA.

Scientists in China have published similar studies with mixed results.

In December 2015, scientists and ethicists at an international meeting held at the National Academy of Sciences (NAS) in Washington said it would be "irresponsible" to use gene editing technology in human embryos for therapeutic purposes, such as to correct genetic diseases, until safety and efficacy issues are resolved.

But earlier this year, NAS and the National Academy of Medicine said scientific advances make gene editing in human reproductive cells "a realistic possibility that deserves serious consideration.

Reporting By Deena Beasley; Editing by Michael Perry

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First editing of human embryos carried out in United States - Reuters

Nearly five years ago, MesotheliomaHelp reported about a breakthrough treatment called gene therapy. At the time, it was touted as the next frontier in medicine, and cancer patients from around the world watched closely in the hopes that the treatment could bring a cure to even the rarest of cancers, such as mesothelioma. Now, all eyes are on the U.S. Food and Drug Administration as it is poised to approve two types of gene therapy.

The Oncologic Drugs Advisory Committee (ODAC) sent its recommendation to the FDA on July 12 for CTL019 (tisagenlecleucel) for the treatment of a form of leukemia. Then, on July 17, the FDA accepted a Biologics Licensing Application from Spark Therapeutics for gene therapy for a rare inherited eye disease that causes blindness, approved the name Luxturna for the treatment, and assigned priority status to the treatment for accelerated review.

To better understand these two pending landmark approvals and the future of gene therapy, MesotheliomaHelp turned to Ricki Lewis, a New York-based geneticist and author.

Its not right for every disease, said Lewis. But it is an approach that can be considered some day along with drugs, surgery and everything else.

Tisagenlecleucel is an investigational chimeric antigen receptor (CAR) T cell therapy from Novartis, developed by researchers at the University of Pennsylvania. The pharmaceutical company wants to use the therapy to treat a rare form of leukemia, B-cell acute lymphoblastic leukemia affecting children and young adults under the age of 25, according to NPR.

Lewis explains that CAR-T therapy is not conventional gene therapy, which has been in clinical trials to treat single-gene diseases since 1990. However, she notes that CAR T cell technology has had astonishing success in treating a form of leukemia and its being tested for multiple myeloma, brain cancer, breast cancer, and soft tissue cancers.

Although both approaches deliver DNA in viruses, classical gene therapy adds a working copy of a single mutant gene, restoring a specific proteins function, says Lewis. Revving up a not-naturally-occurring immune response isnt the same thing as replacing an enzyme, which is what Luxturna does.

According to the National Cancer Institute, in CAR-T treatment, T cells are removed from the patients blood and genetically altered in a lab to have chimeric antigen receptors on their surface. The T cells are then multiplied, into the billions, in the lab and infused back into the patients blood, where they seek out the cancer cells and launch a precise immune attack against them.

Lewis offers the following explanation of CAR-T:

CAR operates like a drone, targeting and obliterating cancer cells. It introduces a gene manufactured to contain instructions for making two immune system components in one, something that doesnt exist in nature: an antibody and a T cell receptor. When delivered in a virus, the CAR enters the persons T cells, which then manufacture the hybrid (chimeric) protein.

The engineered receptor portion guides the T cells to a specific target such as cancerous B cells where the antibody part binds. The action alerts the immune system to respond and kill the cancer cells.

Ultimately, CAR-T, also described as a process that genetically alters a patients own cells to fight cancer, could be used for many more diseases and cancers, and bring an effective treatment to mesothelioma patients.

In a 2013 article for MesotheliomaHelp, Lewis wrote about CAR-T treatment saying, An ingenious technique that has vanquished leukemia in a handful of patients is also being applied to mesothelioma.

Lewis highlighted the CAR-T process being used in a mesothelioma clinical trial from the University of Pennsylvania that uses the doctored T cells, known as chimeric immune receptor (CIR) instead of CAR, against mesothelin, a protein that is found to be in excess in mesothelioma and other cancers. The idea is that T cells led to the mesothelioma cells will attract an immune response, said Lewis.

Find out more about the mesothelioma clinical trial from the University of Pennsylvania here.

In her book The Forever Fix, Lewis followed the journey of the use of gene therapy to restore the vision of a young boy who was nearly blind from a hereditary disorder. The doctors added a working copy of a single defective gene in the New York boys eyes that prevented his eyes from using vitamin A to send visual signals to his brain. The treatment was a success: the boys vision was restored and no further treatments or surgery were required.

Last weeks FDA advisory committees greenlight for CAR technology overshadowed a milestone for what is likely to be the first approval of classic gene therapy for a form of inherited blindness, Lewis told MesotheliomaHelp. Thats the Leber congenital amaurosis type 2 renamed RPE65-mediated inherited retinal dystrophy that I wrote my book about.

In an interview with Lewis last week, Dr. Katherine High, MD, President, Chief Scientific Officer, and a founder of Spark Therapeutics, said of the future of gene therapy:

I hope we will see continued accumulation of successful clinical results in a range of target tissues and continued progress in bringing gene therapy products to licensing. When gene therapy products are licensed, there will be increased interest in the medical community, and that will help to expand opportunities.

Mesothelioma patients typically show disease symptoms years or even decades after exposure to asbestos, a known carcinogen. The cancer is eventually fatal, but aggressive therapy may prolong the lives of patients who are diagnosed early. Approximately 3,000 Americans are diagnosed with the cancer each year.

Getting at the basis of why one person develops mesothelioma and another person doesnt, that is going to hold a clue to really fighting it, Lewis said, referring to a clinical trial conducted at Wake Forest University in 2013 to determine whether some mesothelioma patients are genetically predisposed to developing mesothelioma. Then we will know what to do the gene therapy on.

The pending FDA approvals could bring groundbreaking treatment to cancer patients and to patients with genetic diseases. Perhaps someday, mesothelioma patients will enjoy long, productive lives through gene therapy.

The FDA is not bound to follow the ODACs recommendations, however, the Agency nearly always follows the recommendation. Approval for CTL019 is expected in November. The FDA will decide on Luxturna in January, 2018.

About Ricki Lewis,PhD Ricki Lewis is a science writer with a PhD in genetics. The author of several textbooks and thousands of articles in scientific, medical, and consumer publications, Rickis first narrative nonfiction book, The Forever Fix: Gene Therapy and the Boy Who Saved It, was published by St. Martins Press in March 2012. In addition to writing, Ricki provides genetic counseling for parents-to-be at CareNet Medical Group in Schenectady, NY and teaches Genethics an online course for masters degree students at the Alden March Bioethics Institute of Albany Medical Center.

Read more about gene therapy on Ricki Lewiss DNA Science blog.

Find out more about Ricki Lewis at her website.

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Two Gene Therapy Approaches Pending Approval from FDA Bring Hope to Mesothelioma Community - MesotheliomaHelp.org (blog)

When the groundbreaking geneticist Barbara McClintock was born in Hartford, Connecticut, in 1902, her parents initially named her Eleanor. But they soon felt that the name was too delicate for their daughter and began to call her Barbara instead, which they thought better suited her strong personality. Her parents accurately predicted her determination.

To say that McClintock was a pioneer is an understatement. In 1944, she became the third woman to be elected to the US National Academy of Sciences and the first woman to lead the Genetics Society of America. Shortly afterwards, she discovered that certain genetic regions in maize could jump around the chromosome and, consequently, influence the color of mottled ears of maize with kernels ranging from golden yellow to dark purple. She dubbed these jumping bits of genetic code controlling units, which later became known as transposons or transposable elements. Unfortunately, by the mid-1950s, McClintock began to sense that the scientific mainstream was not ready to accept her idea, and she stopped publishing her research into this area to avoid alienation from the scientific establishment. But scientific ideas can re-emerge and integrate into the mainstream, and 30 years later, McClintock received a Nobel Prize in Physiology or Medicine for her revolutionary insights into these moving chunks of genetic code.

In recent years, medical research has uncovered new evidence showing that moving parts of the genome in humans can contribute to life-threatening diseases ranging from cancer to diabetes. For example, a handful of hemophilia cases have been traced to transposable elements that, at some point before the patient was born, or even, perhaps, conceived, inserted themselves into and disrupted genes that facilitate blood clotting. At the same time, experiments also offer mounting data to suggest that some transposable elementsand the genes that these roving bits of DNA help to resurrecthave beneficial roles.

The study of transposable elements is a hotbed of research, according to Josh Meyer, a postdoctoral fellow who studies these bits of DNA at Oregon Health & Science University in Portland. Way back in the mists of time for the field, the general category of these things was junk DNA, he explains. Now, he says, researchers have begun to understand that transposable elements aren't always neutral genetic components: There's nothing that transposon biologists love more than to have the discussion of whether these things are, on balance, bad for us or good for us.

Since McClintock's breakthrough, researchers have identified different classes of transposable elements in the genomes of every organism in which they have sought them, ranging from fruit flies to polar bears. About 3% of the human genome consists of transposons of DNA origin, which belong to the same class as the ones that McClintock studied in maize. The other type of transposable elements, known as retrotransposons, are more abundant in our genome. These include the transposable elements that originate from viruses and make up as much as 10% of the human genome1. These elements typically trace back many millennia. They arise when viruses integrate into the genome of sperm or egg cells, and thus get passed down from one generation to the next.

The ancient viruses that became 'fossilized' in the genome remain dormant for the most part, and degenerate over time. However, there are hints that they might have the ability to re-emerge and contribute to illnesses that some scientists say could include autoimmune disease and schizophrenia2. In one example, a 2015 study found elevated levels of one embedded virus, known as human endogenous retrovirus K, in the brains of individuals with amyotrophic lateral sclerosis, also known as Lou Gehrig's disease3. However, researchers stress that the data do not yet establish a causal link.

Yet another category of retrotransposons, called long interspersed nuclear elements-1, or LINE-1 for short, make up a whopping 17% or more of the human genome4. When LINE-1 retrotransposons move within the genome of reproductive cells and insert themselves in new places, they can disrupt important genes. Researchers have so far identified more than 120 LINE-1 gene insertions, resulting in diseases ranging from muscular dystrophy to cystic fibrosis5.

Much of the focus on transposable elementsand particularly, on endogenous retroviruses and LINE-1shas centered on the possible negative repercussions of these DNA insertions. But work tracing back to the 1980s has suggested that endogenous retroviruses may also support reproductive function in some way6. In 2000, scientists found that remnants of an ancient virus in the human genome encode a protein called syncytin, which cell experiments indicate is important for placental development7. And although it is not shown definitely, there are also hints that an endogenous retrovirus that became embedded in the DNA of a primate ancestor might help boost the production of the digestive enzyme amylase, which helps to break down starch, in our saliva8, 9.

To peer deeper into the effects of transposable elements in humans, geneticist Nels Elde and his colleagues at the University of Utah in Salt Lake City used CRISPRCas9 gene editing to target an endogenous retrovirus called MER41, thought to come from a virus that integrated into the genome perhaps as far back as 60 million years ago. The scientists removed the MER41 element from human cells cultured in a dish. In humans, MER41 appears near genes involved in responding to interferon, a signaling molecule that helps our immune response against pathogens. Notably, as compared with normal cells, cells engineered to lack MER41 were more susceptible to infection by the vaccinia virus, used to inoculate people against smallpox. The findings, reported last year, suggest that MER41 has a crucial role in triggering cells to launch an immune response against pathogens through the interferon pathway10.

Meyer stresses that these insights elevate the already eminent discoveries by McClintock. I would hope she would be extremely gratified and vindicated, he says. She recognized a type of sort of factor of genomic dynamism that no one else had seen before. And I am firmly convinced that it's going to only become more and more and more central to our understanding of how genomics works.

In 2005, with a freshly minted doctorate in molecular genetics, Nels Elde landed a job as a research fellow in Seattle and was tasked with studying the evolution of the immune system of gibbons, a type of ape. Each morning as he biked to the lab downtown, he would pass the city's zoo and hear its gibbons calling to each other. Occasionally, he would visit the zoo and look at them, but he had no idea at the time that the squirrel monkeys that he also saw there would feature so largely in his future research. At work, Elde's primate investigations focused on the gibbon DNA that he was responsible for extracting and analyzing using sequencing machinery.

Then, six years ago, Elde received his first lab of his own to run, at the University of Utah. He did not expect his team's first discovery there to come so swiftly, or that it would involve transposable elements. Elde had arrived at the university with the intention of learning how cells recognize and defeat invading viruses, such as HIV. But he hadn't yet obtained the equipment that he needed to run experiments, despite already having two employees who were eager to do work, including his lab manager, Diane Downhour. Given the lack of lab tools, the two lab staff members spent their time on their computers, poking around databases for interesting patterns in DNA. After just two weeks of this, Downhour came into Elde's office and told him that they had found a couple of extra copies of a particular gene in New World monkeysspecifically, in squirrel monkeys.

Elde initially brushed off Downhour's insight. I said, 'Why don't you go back to the lab and not worry about it?' he recalls. But a couple of days later, she returned to his office with the idea. I was just in the sort of panicked mode of opening a lab, ordering freezers, trying to set up equipment and hiring people, Elde explains. Diane definitely had to come back and say, 'Come on, wake up here. Pay attention.'

The gene that they detected multiple copies of in squirrel monkeys is called charged multivesicular body protein 3, or CHMP3. Each squirrel monkey seems to have three variants of the gene. By comparison, humans have only the one, original variant of CHMP3. The gene is thought to exist in multiple versions in the squirrel monkey genome thanks to transposable elements. At some point around 35 million years ago, in an ancestor of the squirrel monkey, LINE-1 retrotransposons are thought to have hopped out of the genome inside the cell nucleus and entered the cytoplasm of the cell. After associating with CHMP3 RNA in the cytoplasm, the transposable elements brought the code for CHMP3 back into the nucleus and reintegrated it into the genome. When the extra versions of CHMP3 were copied into the genome, they were not copied perfectly by the cellular machinery, and thus changes were introduced into the sequences. Upon a first look at the data, these imperfections seemed to render them nonfunctional 'pseudogenes'. But as Elde's team delved into the mystery of why squirrel monkeys had so many copies of CHMP3, an intriguing story emerged.

The discovery of pseudogenes is not wholly uncommon. There are more than 500,000 LINE-1 retrotransposons in the human genome11, and these elements have scavenged and reinserted the codes for other proteins inside the cell as well. Unlike with the endogenous retroviral elements in the genome, which can be clearly traced back to ancient viruses, the origin of LINE-1 retrotransposons is murky. However, both types of transposable elements contain the code for an enzyme called reverse transcriptase, which theoretically enables them to reinsert genetic code into the genome in the cell nucleus. This enzyme is precisely what allowed LINE-1 activity to copy CHMP3 back into the genome of the squirrel-monkey ancestor.

Elde couldn't stop thinking about the mystery of why squirrel monkeys had multiple variants of CHMP3. He knew that in humans, the functional variant of the CHMP3 gene makes a protein that HIV uses to bud off of the cell membrane and travel to and infect other cells of the body. A decade ago, a team of scientists used an engineered vector to prompt human cells in a dish to produce a truncated, inoperative version of the CHMP3 protein and showed that the truncated protein prevented HIV from budding off the cells12. There was hope that this insight would yield a new way of treating HIV infection and so prevent AIDS. Unfortunately, the protein also has a role in allowing other important molecular signals to facilitate the formation of packages that bud off of the cell membrane. As such, the broken CHMP3 protein that the scientists had coaxed the cells to produce soon caused the cells to die.

Given that viruses such as HIV use a budding pathway that relies on normal CHMP3 protein, Elde wondered whether the extra, altered CHMP3 copies that squirrel monkeys carry confers some protection against viruses at the cellular level. He coordinated with researchers around the globe, who sent squirrel-monkey blood from primate centers as far-reaching as Bastrop, Texas, to French Guiana. When Elde's team analyzed the blood, they found that the squirrel monkeys actually produced one of the altered versions of CHMP3 they carry. This finding indicated that in this species, one of the CHMP3 copies was a functional pseudogene, making it more appropriately known as a 'retrogene'. In a further experiment, Elde's group used a genetic tool to coax human kidney cells in a dish to produce this retrogene version of CHMP3. They then allowed HIV to enter the cells, and found that the virus was dramatically less able to exit the cells, thereby stopping it in its tracks. By contrast, in cells that were not engineered to produce the retrogene, HIV was able to leave the cells, which means it could theoretically infect many more.

In a separate portion of the experiment Elde's group demonstrated that whereas human cells tweaked to make the toxic, truncated version of CHMP3 (the kind originally engineered a decade ago) die, cells coaxed to make the squirrel-monkey retrogene version of CHMP3 can survive. And by conducting a further comparison with the truncated version, Elde found that the retrogenewhat he calls retroCHMP3in these small primates had somehow acquired mutations that resulted in a CHMP3 protein containing twenty amino acid changes. It's some combination of these twenty points of difference in the protein made by the retrogene that he thinks makes it nontoxic to the cell itself but still able to sabotage HIV's efforts to bud off of cells. Elde presented the findings, which he plans to publish, in February at the Keystone Symposia on Viral Immunity in New Mexico.

The idea that retroCHMP3 from squirrel monkeys can perhaps inhibit viruses such as HIV from spreading is interesting, says Michael Emerman, a virologist at the Fred Hutchinson Cancer Research Center. Having an inhibitor of a process always helps you understand what's important for it, Emerman explains. He adds that it's also noteworthy that retroCHMP3 wasn't toxic to the cells, because this finding could inspire a new antiviral medicine: It could help you to design small molecules or drugs that could specifically inhibit that part of the pathway that's used by viruses rather than the part of the pathway used by host cells.

Akiko Iwasaki, an immunologist at the Yale School of Medicine in New Haven, Connecticut, is also optimistic that the finding will yield progress. What is so cool about this mechanism of HIV restriction is that HIV does not bind directly to retroCHMP3, making it more difficult for the virus to overcome the block imposed by retroCHMP3, Iwasaki says. Even though humans do not have a retroCHMP3 gene, by understanding how retroCHMP3 works in other primates, one can design strategies to mimic the activity of retroCHMP3 in human cells to block HIV replication.

Elde hopes that, if the findings hold, cells from patients with HIV infection might one day be extracted and edited to contain copies of retroCHMP3, and then reintroduced into these patients. Scientists have already used a similar cell-editing approach in clinical trials to equip cells with a variant of another gene, called CCR5, that prevents HIV from entering cells. In these experiments, patients have received infusions of their own cellsmodified to carry the rare CCR5 variant. But although preliminary results indicate that the approach is safe, there is not enough evidence yet about its efficacy. (Another point of concern is that people with the rare, modified version of the CCR5 gene might be as much as 13 times more susceptible to getting sick from West Nile virus than those with the normal version of this gene13.) By editing both retroCHMP3 and the version of CCR5 that prevents HIV entry into cells, Elde suggests, this combination of gene edits could provide a more powerful way of modifying patient cells to treat HIV infection.

You could imagine doing a sort of cocktail genetic therapy in order to block HIV in a way that the virus can't adapt around it, Elde says. His team also plans to test whether retroCHMP3 has antiviral activity against other viruses, including Ebola.

The investigations into how pseudogenes and retrogenes might influence health are ongoing. And there is mounting evidence that the LINE-1 elements that create them are more active than previously thought. In 2015, for example, scientists at the Salk Institute in California reported a previously unidentified region of LINE-1 retrotransposons that are, in a way, supercharged. The region that the researchers identified encodes a protein that ultimately helps the retrotransposons to pick up bits of DNA in the cell cytoplasm to reinsert them into the genome14. The same region also enhances the ability of LINE-1 elements to jump around the genome and thus create variation, adding weight to the idea that these elements might have an underappreciated role in human evolution and in creating diversity among different populations of people.

The active function of transposable elements is more important than many people realize, according to John Coffin, a retrovirus researcher who divides his time between his work at the US National Cancer Institute in Frederick, Maryland, and Tufts University in Boston. They canand havecontributed in important ways to our biology, he says. I think their role in shaping our evolutionary history is underappreciated by many evolutionary biologists.

Squirrel monkeys are not the only animals that might reap protection against viral invaders thanks in part to changes in the genome caused by transposable elements. In 2014, Japanese scientists reported on a chunk of Borna virus embedded in the genome of ground squirrels (Ictidomys tridecemlineatus). The team's results from cellular experiments suggest that this transposed chunk encodes a protein that might interfere with the pathogenicity of external Borna viruses that try to invade these animals15. Humans also have embedded chunks of Borna virus in their genomes. But we don't have the same antiviral version that the ground squirrels haveand we might therefore be less protected against invading Borna viruses.

Other studies of endogenous viruses might have clearer implications for human health, and so scientists are looking at the activity of these transposable elements in a wide range of other animals, including the house cat. This past October, another group of Japanese researchers found that viruses embedded in the genomes of domesticated cats have some capacity to replicate. This replication was dependent on how well the feline cells were able to squelch the endogenous viruses in the genome through a silencing process called methylation16. But perhaps the most striking example of a replicating endogenous retrovirus is in koalas. In the 1990s, veterinarians at Dreamworld, a theme park in Queensland, Australia, noticed that the koalas were getting lymphoma and other cancers at an alarming rate. The culprit turned out to be a retrovirus that was jumping around in the animals' genomes and wreaking havoc. Notably, koalas in the south of the country showed no signs of the retrovirus, which suggests that the virus had only recently begun to integrate into these animals' DNA17.

The risks of transposable elements to human health are a concern when it comes to the tissue transplants we receive from other species, such as from pigs, which have porcine endogenous retroviruses. These embedded viruseswhich have the unfortunate abbreviation PERVscan replicate and infect human cells.

Transplants from pigs, for example, commonly include tissues such as tendons, which are used in ACL-injury repair. But these tissues are stripped of the pig cellsand thus of PERVsso that just the tissue scaffold remains. However, academic institutions and companies are actively designing new ways to use pig tissues in humans. Earlier this year, Smithfield Foods, a maker of bacon, hotdogs and sausages, announced it had launched a new bioscience unit to help supply pig parts to medical companies in the future. Meanwhile, George Church, a Harvard Medical School geneticist and entrepreneur, has formed a company called eGenesis Bio to develop humanized pigs for tissue transplantation. In March, the company announced that it had raised $38 million in venture funding. Church published a paper two years ago showing that his team had edited out key bits of 62 PERVs from pig embryos, disrupting the PERVs' replication process and reducing their ability to infect human cells by 1,000-fold18.

Whereas Church and other scientists have tried disrupting endogenous retroviruses in animal genomes, researchers have also experimented with resurrecting them: a decade ago, a group of geneticists in France stirred up some controversy when the researchers recreated a human endogenous retrovirus by correcting the mutations that had rendered it silent in the genome for millennia. The scientists called it the 'Phoenix' virus, but it showed only a weak ability to infect human cells in the lab19. There was, perhaps unsurprisingly, pushback against the idea of resurrecting viruses embedded in our genomeno matter how wimpy the resulting viral creation.

But emerging data suggest that the retroviruses buried in the human genome might not be quite as dormant as we thought. The ability for these endogenous retroviruses to awaken from the genome is more widespread than has been previously appreciated, says virologist Rene Douville at the University of Winnipeg in Canada. She views this phenomenon as being the rule, rather than the exception within the cell: These retroelements are produced from the genome as part of the cell's normal function to varying degrees.

Interestingly, the cellular machinery involved in keeping cancer at bay might also have a connection to transposable elements. One in three binding sites in the human genome for the important tumor-suppressor protein p53 are found within endogenous retroviruses in our DNA20. And last year, a team led by John Abrams at University of Texas Southwestern Medical Center in Dallas offered preliminary evidence that p53 might do its work by perhaps keeping embedded retroelements in check21.

When I first started openly publicly talking about this story, some of my colleagues here who are in the cancer community said, 'Hey, that's cute, but it can't be true. And the reason it can't be true is that we would know this already,' Abrams recalls. The reason it wasn't seen before, he explains, is that many genetic analyses throw out repeated sequenceswhich often consist of retroelements. So his team had to go dumpster diving in the genetic databases for these sequences of interest to demonstrate the link to p53. Abrams suspects that when p53 fails to keep retrotransposons at bay, tumors might somehow arise: The next question becomes, 'How do you get to cancer?' Abrams says that this is an example of what he calls transposopathies.

Not all scientists are convinced of a causal link between p53 and retroelements in cancer. My question is, if p53 is so vital in suppressing retrotransposon activity in cancer, why do we not find evidence of dysregulated retrotransposons inserting copies of themselves into the tumor genome more often? asks David Haussler, a genomics expert at the University of California, Santa Cruz. Most tumors have p53 mutations, yet only a very small percentage of tumors show evidence of significantly dysregulated rates of new retrotransposon copy insertion.

Still, there are others interested in exploring whether ancient viruses might reawaken in cancer or have some other role in this disease. Five years ago, scientists at the University of Texas MD Anderson Cancer Center reported that a type of viral protein produced by the human endogenous retrovirus type K (HERV-K) is often found on the surface of breast cancer cells. In a mouse experiment, they showed that cancers treated with antibodies against this protein grew to only one-third of the size of tumors that did not receive this therapy22.

But some cancer scientists are thinking about co-opting endogenous retroviruses to use against cancer. Paul Bieniasz of the Rockefeller University in New York City gained insight into this approach by studying human endogenous retrovirus type T (HERV-T)an ancient virus that spread for 25 million years among our primate ancestors until its extinction roughly 11 million years ago and at some point became fossilized in our DNA lineage. In April, his group found that a particular HERV-T encodes a protein that blocks a protein called monocarboxylate transporter 1, which is abundant on the surface of certain types of cancer cells23. It's thought that monocarboxylate transporter 1 has a role in enabling tumors to grow. Blocking it could help to stymie the expansion of malignancies, Bieniasz speculates. He and his colleagues are now trying to build an 'oncolytic virus' that uses elements of HERV-T to treat cancer.

The idea that new viruses might still be trying to creep into our genomes is a scary one, even if they don't appear very effective at achieving this. One of the most recent to integrate into our genome in a way that it is passed down from generation to generation is human endogenous retrovirus type K113 (HERV-K133), which sits on chromosome 19. It's found in only about one-third of people worldwide, most of whom are of African, Asian or Polynesian background. And researchers say that it could have integrated into the genome as recently as 200,000 years ago6.

Although experts remain skeptical that a virus will integrate into the human genome again anytime soon, other transposable elements, such as LINE-1s, continue to move around in our DNA. Meanwhile, the field that Barbara McClintock seeded more than half a century ago is growing quickly. John Abrams, who is studying retroelements, says that we're only just beginning to understand how dynamic the genome is. He notes that only recently have people begun to appreciate how the 'microbiome' of bacteria living in our guts can influence our health. We're really an ecosystem, Abrams says of the gut, and the genome is the same way. There is the host DNAbelonging to usand the retro-elements it contains, he explains, and there's this sort of productive tension that exists between the two.

This article is reproduced with permission and wasfirst publishedon July 11, 2017.

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Medicine's Movable Feast: What Jumping Genes Can Teach Us about Treating Disease - Scientific American

This article is authored by the Mayo Clinic Center for Individualized Medicine. The mission of the Center is to discover and integrate the latest in genomic, molecular and clinical sciences into personalized care for patients.

New technology is reshaping prenatal screening to assess the health of a developing baby. Now pregnant women can have their baby initially screened for genetic disorders, such as Down syndrome, through the use of a newer blood test that evaluates DNA present in the mothers blood stream. Another test for couples planning a family uses a single blood sample to assess whether future children might be at risk for developing a genetic disease.

Its an exciting time in perinatal testing, explains Myra Wick, M.D., Ph.D. DNA sequencing and molecular technology have improved and become more cost effective. These tests are important for family planning before pregnancy as well as planning for the care of a baby who is found to have a genetic disorder during pregnancy.

Researchers from Mayo Clinic and the Center for Individualized Medicine have helped implement several of these tests, which use a personalized medicine approach to perinatal screening. Three state-of-the-art perinatal genetic tests are becoming more widely available to expectant parents.

Mayo Medical Laboratories recently launched a blood test to screen for the most common chromosome disorders diagnosed in pregnancy, such as Down syndrome. Its known as a cell-free DNA test. It screens the mothers blood that contains DNA from the baby, looking for genetic disorders in the fetus. The new test generally has a higher detection rate and fewer false positives than traditional screening tests.

Prior to this new test, mothers had the option of traditional first trimester screening, which is a blood test and ultrasound, or second trimester screening, which is a blood test. In general, the cell free DNA blood test can be used in place of the traditional first and second trimester screening, explains Dr. Wick. It is important to remember that the cell free DNA testing is a screening test, and abnormal results should be followed up with additional testing.

The out-of-pocket cost for the new blood test varies depending on insurance coverage, and the specific laboratory performing the testing; a general estimate is approximately $350. Results are usually ready within one week.

2. Expanded carrier screening

In the past, couples had genetic screening based on family history of a genetic disorder, or if they were part of an ethnic group at risk for certain inherited diseases. Previous tests only screened for a small defined group of genetic disorders. Those tests didnt help couples who were uncertain of their ethnic heritage, plus the tests were very limited in scope.

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Its an exciting time in perinatal testing. DNA sequencing and molecular technology has improved and become more cost effective. These tests are important for family planning prior to pregnancy as well as planning for the care of a child who is found to have a genetic disorder during pregnancy. - Dr. Myra Wick

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Now couples may choose a more comprehensive test that looks for 100 or more genetic disorders. Its called expanded carrier screening. This test is done with a blood sample from each prospective parent.

Expanded carrier screening looks at multiple genes associated with genetic diseases. Most of the disorders included on an expanded carrier screen are inherited in an autosomal recessive manner. This means that the parents are carriers of the disorder, with one normal copy of the gene and one abnormal copy of the gene. Carriers of an autosomal recessive disorder do not typically have signs or symptoms of the disease. A child is affected with an autosomal recessive disorder when he or she inherits one abnormal copy of the gene from mom, and one abnormal copy of the gene from dad. Approximately 5% of couples who undergo expanded carrier screening are found to be carriers for the same disorder, and at risk for having an affected says Dr. Wick.

Depending upon insurance coverage, the test costs approximately $350. Test results are returned within one to two weeks.

3. Whole exome sequencing (WES)

In rare cases, an ultrasound during pregnancy reveals that the baby has several medical problems. Traditional genetic testing may not identify a diagnosis. Now whole exome sequencing (WES), which looks at most of the genes linked to growth and health, can be used to evaluate the fetuss condition. It can provide a diagnosis in 30 percent of cases.

For this testing, an amniocentesis is performed first to obtain DNA for genetic analysis.

We are beginning to use WES even before the baby is born. Results can be used to plan for care of an infant who may be born with several complex medical concerns. In addition, parents can use this information for future family planning, says Dr. Wick.

Whole exome sequencing is expensive, with typical costs of approximately $8,000, depending upon the specific test and insurance coverage. Results from this more complex screening usually take several weeks, depending upon the specific test being used.

Dr. Wicks suggests that you ask your health care provider about genetic testing and recommends that all prospective and expectant parents consult with a medical geneticist or genetic counselor before genetic screening.

If your provider is at a large medical center, genetic counseling should be available. At smaller facilities, your primary provider may order initial blood tests, but you may be referred to a larger facility if test results indicate you need genetic counseling.

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3 Genetics Tests To Improve Prenatal Screening - HuffPost

A Phase 2/3 clinical trial of elamipretide,a potential treatment for a rare mitochondrial disease known asBarth syndrome, is now enrolling patients, the therapys developer,Stealth BioTherapeutics, announced.

The TAZPOWER study (NCT03098797) will be conducted in McKusick-Nathans Institute of Genetic Medicine, at the Johns Hopkins University School of Medicine, and is expected to include 12 patients, ages 12 or older, with genetically confirmed Barth syndrome and stable symptoms, butimpaired walking ability.

Our understanding of Barth syndrome and how it manifests has evolved significantly, but current treatment efforts are still limited to the management of symptoms, Hilary Vernon, anassistant professor of pediatrics at the McKusick-Nathans Institute and the studys primary investigator, said in a press release. The initiation of TAZPOWER represents an important milestone in the potential development of a disease-specific treatment option.

Barth syndrome is a rare inherited mitochondrial disease that is almost exclusive to males. This disease is characterized by cardiac abnormalities, skeletal muscle weakness, recurrent infections due to low white blood cell (immune cell) counts, and delayed growth. It is caused by caused by genetic mutations in the TAZ gene, which encodes the protein tafazzin that is essential for the normal functioning of mitochondria.

The severe problems experienced by patients with Barth syndrome are caused by misshapen and dysfunctional mitochondria, which reduce the energy production in the affected tissues. The resulting muscle weakness can lead to severe fatigue, heart failure and death, said Doug Weaver, chief medical officer at Stealth. In this study, we hope to show that elamipretide may have clinical benefit by improving function in these affected mitochondria.

Elamipretidewas designed to restore mitochondrias ability to work as the cells power source. Due to its capacity to penetrate the inner membrane of mitochondria, the therapy as the potential to reduce the levels of damaging oxidative stress produced by mitochondrias dysfunctional activity.

TAZPOWER trial is a placebo-controlled crossover study, designed to evaluate the effects of daily administration of elamipretide in patients with Barth syndrome. All participants will receive single daily subcutaneous injections of elamipretide or placebo for 12 weeks, followed by a four-week wash-out period. This will then be followed by additional 12 weeks of therapy, but this time the patients will switch the treatment received, with those previously givenelamipretide now receivinga placebo and vice-versa.

The drugs efficacy will be measured by changes in the distance that patients are able to walk during the 6-minute walk test (6MWT). Secondary endpoints will include other functional assessments (of muscle strength, balance, etc.), patient-reported outcomes, and overall treatment safety.

This study underscores our commitment to develop elamipretide for the treatment of rare genetic mitochondrial diseases, said Reenie McCarthy, Stealths chief executive officer.

Excerpt from:
Phase 2/3 Trial of Elamipretide to Treat Barth Syndrome Now Enrolling Patients - Mitochondrial Disease News

July 26, 2017

An article published in Experimental Biology and Medicine (Volume 242, Issue 13, July, 2017) reports that gene therapy may be used to as an intermediate therapy for newborns with surfactant protein deficiencies until lung transplantation becomes an option. The study, led by Dr. David Dean in the Division of Neonatology at the University of Rochester in Rochester NY reports that electroporation-mediated delivery of the surfactant B gene to deficient mice improves lung function and survival.

Surfactant is present in the lungs of all humans. This important protein makes it easier for people to breath. Without it, lungs would collapse with each breath. Surfactant protein B (SPB) deficiency is a rare but fatal disease that affects full term babies after an apparently uncomplicated pregnancy and delivery. Babies with SBP deficiency have severe breathing problems from birth, and die in infancy even with aggressive medical treatment. To date the only effective treatment is a lung transplant. Given how quickly these babies become ill, and the limited number of available organs, transplantation is often not even an option.

The most promising therapy for this devastating disease is replacement of the absent SPB gene, a process called gene therapy. Gene therapy approaches using viral-based delivery techniques have not achieved therapeutic levels of SPB protein and induce inflammation, which can exacerbate the disease. The current study used electroporation-based delivery techniques which result in higher levels of transgene expression and are well-tolerated even in animals with existing lung injury. Delivery of SPB DNA into the lung cells of SPB-deficient mice reduced lung inflammation, improved lung function, and extended survival. Since the DNA is eventually silenced, SPB expression does not last forever and this is approach cannot provide a cure.

Dr. Barnett, a neonatology fellow and coauthor said "although this treatment does not provide lifelong correction, our data suggest that this may be a useful approach for improving the survival and stability of infants until lung transplant can occur." Dr. Dean added "we are excited to help optimize an approach that may treat and someday even cure this and other devastating diseases."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said, "Dean and colleagues provide evidence that gene therapy may restore surfactant activity in SPB deficiency for sufficient time to allow lung transplants in a greater number of affected neonates. This is represents an important advance in this field of research."

Explore further: Gene delivery to the lung can treat broad range of diseases within and beyond the lung

Data demonstrating sustained protein expression five years after a single intramuscular injection of a gene-based therapy for the treatment of alpha-1 antitrypsin (AAT) deficiency also shows improvements in multiple indicators ...

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Gene therapy to correct surfactant protein B deficiency in newborns - Medical Xpress

July 26, 2017 A microscope image showing glia cells and neurons in the eye's retina. Credit: Tom Reh lab/UW Medicine

Scientists have successfully regenerated cells in the retina of adult mice at the University of Washington School of Medicine in Seattle.

Their results raise the hope that someday it may be possible to repair retinas damaged by trauma, glaucoma and other eye diseases. Their efforts are part of the UW Medicine Institute for Stem Cell and Regenerative Medicine.

Many tissues of our bodies, such as our skin, can heal because they contain stem cells that can divide and differentiate into the type of cells needed to repair damaged tissue. The cells of our retinas, however, lack this ability to regenerate. As a consequence, injury to the retina often leads to permanent vision loss.

This is not the case, however, in zebrafish, which have a remarkable ability to regenerate damaged tissue, including neural tissue like the retina. This is possible because the zebrafish retina contains cells called Mller glia that harbor a gene that allows them to regenerate. When these cells sense that the retina has been injured, they turn on this gene, called Ascl1.

The gene codes for a type of protein called a transcription factor. It can affect the activity of many other genes and, therefore, have a major effect on cell function. In the case of the zebrafish, activation of Ascl1 essentially reprograms the glia into stem cells that can change to become all the cell types needed to repair the retina and restore sight.

The team of researchers in the new study were led by Tom Reh, University of Washington School of Medicine professor of biological structure. The scientists wanted see whether it was possible to use this gene to reprogram Mller glia in adult mice. The researchers hoped to prompt a regeneration that doesn't happen naturally in mammal's retina.

Their research findings appear online July 26 in the journal Nature. The lead author is Nikolas Jorstad, a doctoral student in the Molecular Medicine and Mechanisms of Disease program at the University of Washington.

Like humans, mice cannot repair their retinas. Jorstad said that to conduct their experiment, the team "took a page from the zebrafish playbook." They created a mouse that had a version of the Ascl1 gene in its Mller glia. The gene was then turned on with an injection of the drug tamoxifen.

Earlier studies by the team had shown that when they activated the gene, the Mller glia would differentiated into retinal cells known as interneurons after an injury to the retina of these mice. These cells play a vital role in sight. They receive and process signals from the retina's light-detecting cells, the rods and the cones, and transmit them to another set of cells that, in turn, transfer the information to the brain.

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In their earlier research, however, the researchers found that activating the gene worked only during the first two weeks after birth. Any later, and the mice could no longer repair their retinas. Reh said that at first they thought another transcription factor was involved. Eventually they determined that genes critical to the Mller glia regeneration were being blocked by molecules that bind to chromosomes. This is one way cells "lock up" genes to keep them from being activated. It is a form of epigenetic regulationthe control of how and when parts of the genome operate.

In their new paper, Reh and his colleagues show that, by using a drug that blocks epigenetic regulation called a histone deacetylase inhibitor, activation of Ascl1 allows the Mller glia in adult mice to differentiate into functioning interneurons. The researchers demonstrated that these new interneurons integrate into the existing retina, establish connections with other retinal cells, and react normally to signals from the light-detecting retinal cells.

Reh said his team hopes to find out if there are other factors that can be activated to allow the Mller glia to regenerate into all the different cell types of the retina. If so, it might be possible, he said, to develop treatments that can repair retinal damage, which is responsible for several common causes of vision loss.

Explore further: Study helps explain how zebrafish recover from blinding injuries

More information: Nikolas L. Jorstad et al, Stimulation of functional neuronal regeneration from Mller glia in adult mice, Nature (2017). DOI: 10.1038/nature23283

Journal reference: Nature

Provided by: University of Washington

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Scientists regenerate retinal cells in mice - Medical Xpress