Category Archives: Gene Medicine

Solast week the feds may have dashedUC Berkeleys billion-dollar dreams when it decided not to give the universitypatent rights over CRISPR-Cas9, a revolutionary gene-editing technology.

The Feb. 15ruling from the U.S. Patent and Trademark Office let Berkeleys rivaltheBroad Institutejointly owned by Harvard and MITkeep itsexisting patents issued in 2014.UC Berkeleyhas yet to say whether or not it will appeal.

Berkeley was seeking to have some of those patents repealedbecause the university says they conflict with its pending patent application for CRISPR.

The judges reasoned that Berkeleys patent request doesnt affect Broads existing patents because the two are based on different gene editing techniques.

Berkeleys patent request is for editing genes in bacteria, whereas Broads existing patents are for editing genes in eukaryotic cells, i.e. cells found in plants and animals, including humans.

But Berkeleyargues that its research toolcan easily be extended to use in non-bacterial cells.

That distinction is key since potentially lucrative applications of gene editing in medicine and health will involve eukaryotic cells found in humans.

UC Berkeley biologist Jennifer Doudna, who is credited with co-inventingCRISPR-Cas9 now has two options:

1) Appeal to the U.S. Court of Appeals for the Federal Circuit 2) Go back to the U.S. Patent and Trademark Office

If Berkeley appeals, the court could overrule the patent office decision in favor of Berkeley.

If Berkeley loses, it could go backto the patent office, where itcould be required to narrow itsclaims, i.e., specifying that its technique is only intended to be used in bacteria.

Or it could get a broad patentthat still doesnt specifyhow to use CRISPRin eukaryotic cells. But according to Jacob Sherkow, a law professor at New York Law School, that could lead to future legal challenges.

Its not going to be that strong because anyone who wants to challenge it later can say, that patent doesnt disclose how to use the tool in eukaryotic cells,' says Sherkow.

And the money is in altering those specific cells.

So whats next? Only Berkeley knows; the university has said it will carefully consider all options.

Science journalists are abuzz about what this means for biotech. Heres a sampling of what theyre saying:

1.Berkeley + Broad = VirtualMonopoly on CRISPR-Cas9 (Gizmodo)

Why does this matter? While academic researchers can still use CRISPR for free, companies hoping to harness the gene editing tool to fight disease, solve agricultural problems, or for myriad other potential applications, may have to pay not one, but both institutions, a hefty fee. Its a decision that has caused some to wonder whether the rights to such revolutionary technology dont really belong to a third party: the people.

2. Could the Case Encourage Scientiststo Be Less Honest?(STAT)

The patent judges concluded that the inventors themselves were uncertain about making CRISPR work in human cells.

That could send a terrible message to scientists, said Dr. Robert Cook-Deegan of Arizona State University, an expert on legal and ethical issues surrounding biotechnology. I hope this does not become the poster child that patent offices use to coach scientists not to be honest about uncertainties about their discoveries, he said. The fact that Doudnas quotes were used by the judges mainly tells me Doudna was being honest. I hope scientists will continue to be honest and not succumb to being told they cant say things that might undermine a broad patenting strategy.

3. Fogettaboutit, Companies Can SidestepBerkeleyand Broad(Nature)

Researchers in academia and industry have been pushing CRISPR gene editing beyond the scope of the Broad and Berkeley patents.

Both patent families cover the use of CRISPRCas9, which relies on the Cas9 enzyme to cut DNA. But there are alternatives to Cas9 that provide other functions, and a way to sidestep the BerkeleyBroad patent fight.

One attractive alternative is Cpf1, an enzyme that may be simpler to use and more accurate than Cas9 in some cases. The Broad has already filed patents on applications of Cpf1 in gene editing, and has licensed them to biotech company Editas Medicine in Cambridge, Massachusetts.

Remember, my friends, if UC Berkeley appeals, this whole process could last through 2020. Or longer.

Lindsey Hoshaw is an interactive producer for KQED Science. Before joining KQED, Lindsey was a science correspondent for The New York Times, The Boston Globe, Forbes and Scientific American. On Twitter @lindseyhoshaw

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CRISPR Patent Ruling: 3 Different Takes - KQED

A newly discovered type of genetic mutation that occurs frequently in cancer cells may provide clues about the diseases origins and offer new therapeutic targets, according to new research from Weill Cornell Medicine and the New York Genome Center.

Using next-generation sequencing technology, scientists have previously traced cancers roots to mutations that disrupt the sequence of proteins. As a result, the cell either creates hyperactive or dysfunctional versions of proteins, or fails to produce them at all, leading to cancer. Now, a study published Jan. 12 in Cell illuminates a possible new type of driver of the disease: small (one-50 letter) insertions or deletions of DNA sequence, also called indels, in regions of the genome that do not code for protein.

Dr. Marcin Imielinski Photo credit: John Abbott

Those non-coding regions are still important because they contain sequences that affect how genes are regulated, which is critical for normal cell development, said lead author Dr. Marcin Imielinski, an assistant professor of pathology and laboratory medicine at Weill Cornell Medicine and a core member at the New York Genome Center. We already know they are biologically important. The question is whether they can impact cancer development.

In the study,Dr.Imielinski and colleagues from the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute analyzed sequencing data from several publicly available databases of tumor samples, focusing on the 98 percent of the genome that does not code for protein. They initially looked at lung adenocarcinoma, the most common type of lung cancer, and found that the most frequent indel-mutated regions in their genomes landed in genes encoding surfactant proteins. Though these genes are essential for healthy lung function, they had not previously been associated with lung cancer. However, they are highly and specifically expressed by the cell type that gives rise to lung adenocarcinoma.

The researchers then looked at the genomes of 12 other cancer types and found similar patterns in liver, stomach and thyroid tumors. In each cancer, noncoding indels clustered in genes that are critical to organ function, but had not been associated with the cancer, said Dr. Imielinski, who is also an assistant professor of computational genomics in theHRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicineand a member of theSandra and Edward Meyer Cancer Centerat Weill Cornell Medicine.

This image shows genetic mutations (blue) in the context of their surrounding DNA sequence, highlighting a sequence motif (red) that Dr. Imielinski discovered.

Most strikingly, these non-coding indels are very common, occurring in 20-50 percent of the associated cancers. They occur as frequently as the most famous cancer-causing mutations, said Dr. Imielinski, who is a paid consultant for the company 10X Genomics, which sells devices and technology to analyze genetic information. Any gene or any sequence that mutated at this frequency has been shown to play a causal role in cancer. That would be an exciting outcome, if we can prove it.

Even if these mutations are not shown to cause cancer, they can be used in the future to improve cancer diagnosis and treatment. These mutations can be biomarkers that help us to diagnose a cancer early, or they could be used to pinpoint a primary cancer when there are metastases and we cant find the original cancer, Dr. Imielinski said. There are a lot of potential clinical implications from these findings.

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New Type of Genetic Mutation Identified in Cancer - Cornell Chronicle

February 23, 2017 Many cells in the brain express two copies of each gene, one inherited from mom and one from dad. Others express just one copy. If the single copy happens to carry a genetic mutation, it may cause the cell to become sick. The discovery from the University of Utah offers a previously undescribed nuanced view of genetics that has consequences at the cellular level. Credit: Christopher Gregg

Most kids say they love their mom and dad equally, but there are times when even the best prefers one parent over the other. The same can be said for how the body's cells treat our DNA instructions. It has long been thought that each copy - one inherited from mom and one from dad - is treated the same. A new study from scientists at the University of Utah School of Medicine shows that it is not uncommon for cells in the brain to preferentially activate one copy over the other. The finding breaks basic tenants of classic genetics and suggests new ways in which genetic mutations might cause brain disorders.

In at least one region of the newborn mouse brain, the new research shows, inequality seems to be the norm. About 85 percent of genes in the dorsal raphe nucleus, known for secreting the mood-controlling chemical serotonin, differentially activate their maternal and paternal gene copies. Ten days later in the juvenile brain, the landscape shifts, with both copies being activated equally for all but 10 percent of genes.

More than an oddity of the brain, the disparity also takes place at other sites in the body, including liver and muscle. It also occurs in humans.

"We usually think of traits in terms of a whole person, or animal. We're finding that when we look at the level of cells, genetics is much more complicated than we thought," says Christopher Gregg, Ph.D., assistant professor of neurobiology and anatomy and senior author of the study which publishes online in Neuron on Feb. 23. "This new picture may help us understand brain disorders," he continues.

Among genes regulated in this unorthodox way are risk factors for mental illness. In humans, a gene called DEAF1, implicated in autism and intellectual disability, shows preferential expression of one gene copy in multiple regions of the brain. A more comprehensive survey in primates, which acts as a proxy for humans, indicates the same is true for many other genes including some linked to Huntington's Disease, schizophrenia, attention deficit disorder, and bipoloar disorder.

What the genetic imbalance could mean for our health remains to be determined, but preliminary results suggest that it could shape vulnerabilities to disease, explains Gregg. Normally, having two copies of a gene acts as a protective buffer in case one is defective. Activating a gene copy that is mutated and silencing the healthy copy - even temporarily - could be disruptive enough to cause trouble in specific cells.

Supporting the idea, Gregg's lab found that some brain cells in transgenic mice preferentially activate mutated gene copies over healthy ones. "It has generally been assumed that there is correlation between both copies of a gene," says Elliott Ferris, a computer scientist who co-led the study with graduate student Wei-Chao Huang. Instead, they found something unexpected. "We developed novel methods for mining big data, and discovered something new," Huang explains.

The investigators screened thousands of genes in their study, quantifying the relative levels of activation for each maternal and paternal gene copy and discovered that expression of the two is different for many genes. Surprised by what they saw, they developed statistical methods to rigorously test their validity and determined that they were not due to technical artifacts, nor genetic noise. Following up on their findings, they examined a subset of genes more closely, directly visualized imbalances between gene copies at the cellular level in the mouse and human brain.

Results from Gregg and colleagues build on previous research, expanding on scenarios in which genes play favorites. Imprinted genes and X-linked genes are specific gene categories that differentially activate their maternal and paternal gene copies. Studies in cultured cells had also determined that some genes vary which copy they express. The results from this study, however, suggests that silencing one gene copy may be a way in which cells fine tune their genetic program at specific times during the lifecycle of the animal, or in discrete places.

"Our new findings reveal a new landscape of diverse effects that shape the expression of maternal and paternal gene copies in the brain according to age, brain region, and tissue type," explains Gregg. "The implication is a new view of genetics, one that starts up close."

Explore further: Genetic tug of war in brain subregions influences parental control over offspring behavior

More information: The study publishes in Neuron as "Diverse Non-Genetic Allele Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain". DOI: 10.1016/j.neuron.2017.01.033 , http://www.cell.com/neuron/fulltext/S0896-6273(17)30057-0

Not every mom and dad agree on how their offspring should behave. But in genetics as in life, parenting is about knowing when your voice needs to be heard, and the best ways of doing so. Typically, compromise reigns, and ...

When a child is conceived, he or she receives DNA from both parents. The child's own genome thus consists of a maternal and a paternal genome. However, some genesabout 100 out of the 20,000 encoded genes are exclusively ...

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Playing favorites: Brain cells prefer one parent's gene over the other's - Medical Xpress

A study from Massachusetts General Hospital (MGH) researchers has found that a pattern of gene variants associated with an apple-shaped body type.

In this body type, weight is deposited around the abdomen, rather than in the hips and thighs.This body shape increases the risk for type 2 diabetes and coronary heart disease, as well as the incidence of several cardiovascular risk factors.

[W]e call [this condition] abdominal adiposity, says Sekar Kathiresan, MD, director of the MGH Center for Genomic Medicine. We tested whether genetic predisposition to abdominal adiposity was associated with the risk for type 2 diabetes and coronary heart disease and found that the answer was a firm yes.

No association was found between the genetic risk score and lifestyle factors, and testing confirmed that only the abdominal adiposity effects of the identified gene variants were associated with cardiometabolic risk.

The lack of association between the body type genetic risk score and confounding factors such as diet and smoking provides strong evidence that abdominal adiposity itself contributes to causing type 2 diabetes and heart disease, says lead author Connor Emdin, of the MGH Center for Genomic Medicine and the Cardiology Division.

[The study can be found here.]

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Gene variants associated with body shape increase risk of heart disease, type 2 diabetes

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Diabetes, heart-disease risks rise with 'apple-shape' body gene variant - Genetic Literacy Project

February 23, 2017 This visual abstract depicts the findings of McCoy et al., who show genome-wide interrogation of the functional differences between modern human and Neanderthal alleles reveals that Neanderthal-inherited sequences are not silent remnants of ancient interbreeding but have a measurable impact on gene expression that may contribute to phenotypic variation in modern humans. Credit: McCoy et al./Cell 2017

The last Neanderthal died 40,000 years ago, but much of their genome lives on, in bits and pieces, through modern humans. The impact of Neanderthals' genetic contribution has been uncertain: Do these snippets affect our genome's function, or are they just silent passengers along for the ride? In Cell on February 23, researchers report evidence that Neanderthal DNA sequences still influence how genes are turned on or off in modern humans. Neanderthal genes' effects on gene expression likely contribute to traits such as height and susceptibility to schizophrenia or lupus, the researchers found.

"Even 50,000 years after the last human-Neanderthal mating, we can still see measurable impacts on gene expression," says geneticist and study co-author Joshua Akey of the University of Washington School of Medicine. "And those variations in gene expression contribute to human phenotypic variation and disease susceptibility."

Previous studies have found correlations between Neanderthal genes and traits such as fat metabolism, depression, and lupus risk. However, figuring out the mechanism behind the correlations has proved difficult. DNA can be extracted from fossils and sequenced, but RNA cannot. Without this source of information, scientists can't be sure exactly if Neanderthal genes functioned differently than their modern human counterparts. They can, however, look to gene expression in modern humans who possess Neanderthal ancestry.

In this study, researchers analyzed RNA sequences in a dataset called the Genotype-Tissue Expression (GTEx) Project, looking for people who carried both Neanderthal and modern human versions of any given geneone version from each parent. For each such gene, the investigators then compared expression of the two alleles head-to-head in 52 different tissues.

"We find that for about 25% of all those sites that we tested, we can detect a difference in expression between the Neanderthal allele and the modern human allele," says the study's first author, UW postdoctoral researcher Rajiv McCoy.

Expression of Neanderthal alleles tended to be especially low in the brain and the testes, suggesting that those tissues may have experienced more rapid evolution since we diverged from Neanderthals approximately 700,000 years ago. "We can infer that maybe the greatest differences in gene regulation exist in the brain and testes between modern humans and Neanderthals," says Akey.

One example uncovered by this study is a Neanderthal allele of a gene called ADAMTSL3 that decreases risk of schizophrenia, while also influencing height. "Previous work by others had already suggested that this allele affects alternative splicing. Our results support this molecular model, while also revealing that the causal mutation was inherited from Neanderthals," says McCoy. Alternative splicing refers to a process in which mRNAs are modified before they leave the cell's nucleus. When the Neanderthal mutation is present, the cell's machinery removes a segment of the mRNA that is expressed in the modern human version. The cell ends up making a modified protein because of a single mutation from a Neanderthal ancestor.

The connection between that modified protein, height, and schizophrenia still requires more investigation, but it's an example of how small differences between modern humans and Neanderthals can contribute to variation in people.

"Hybridization between modern humans and Neanderthals increased genomic complexity," explains Akey. "Hybridization wasn't just something that happened 50,000 years ago that we don't have to worry about anymore. Those little bits and pieces, our Neanderthal relics, are influencing gene expression in pervasive and important ways."

Next steps may include investigating whether Denisovansanother species of hominins that crossbred with modern humansare contributing to gene expression, as well as applying the side-by-side method of expression analysis more broadly. For this study, McCoy and his colleagues had to develop a new statistical approach to sift through the immense amount of RNA data, but the same technique could be used to compare gene expression differences between modern human alleles.

Explore further: Long ago humans and Neanderthals Interbred: What happened to Neanderthal genes?

More information: Cell, McCoy et al.: "Impacts of Neanderthal-introgressed sequences on the landscape of human gene expression" http://www.cell.com/cell/fulltext/S0092-8674(17)30128-9 , DOI: 10.1016/j.cell.2017.01.038

Journal reference: Cell

Provided by: Cell Press

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Neanderthal DNA contributes to human gene expression - Phys.Org

Crowd control: Nearly 4 percent of people carry at least one genetic variant tied to a serious medical condition.

brainmaster / Getty Images

Most adults with genetic variants tied to certain conditions, such as heart disease or cancer, go undiagnosed, according to a study of more than 50,000 people1.

The variants silence leaves these people unaware of their risk of developing the conditions later in life, says lead investigator David Carey, director of the Weis Center for Research at Geisinger Health System in Danville, Pennsylvania.

Careys team looked for genetic variants associated with 27 chronic conditions. The list of conditions does not include autism, but does include tuberous sclerosis complex. As many as half of all people with tuberous sclerosis complex have autism. Other teams are studying the same population to gauge the effects of variants linked to autism.

The value lies in the huge population, all captured within the same healthcare system. Its really fantastic, says Dan Arking, associate professor of genetic medicine at Johns Hopkins University in Baltimore, Maryland, who was not involved in the new work.

The variants in the study are clinically significant: Some increase the risk of the linked condition by up to 70 percent. But variants interact with many other genetic and environmental factors, and these interactions may cause the conditions features to be more or less severe or even absent.

People used to say anytime there is a [spontaneous] variant or something really rare, that it must cause disease, says Arking. The new study instead suggests that, on the contrary, some rare variants have weak ties to conditions such as autism, he says. The results appeared 23 December in Science2.

Carey and his team looked at data from the MyCode Community Health Initiative, launched in 2007 by Geisinger Health System in central Pennsylvania. MyCode researchers have collected DNA samples and up to 14 years worth of medical records from the participants.

The researchers probed the 50,726 participants genomes for inserted or deleted sequences, and for single nucleotide variants, called SNVs, in the code. Their analysis revealed that each individual harbors about 21,409 SNVs, consistent with findings from previous studies.

The researchers then narrowed their analysis to 76 genes known to contribute to life-threatening conditions such as cancer or cardiovascular disease. The list includes three genes tied to tumor growth and to autism: PTEN, TSC1 and TSC2. (Clinicians are obligated to counsel individuals with variants in any of these 76 genes.)

Nearly 4 percent of the general population carries variants in at least one of these genes, the researchers found. But more than one-third of these people show no symptoms and have no family history of the linked condition. For example, most of the individuals who carry a variant linked to an inherited condition that causes high cholesterol have normal cholesterol levels, according to a second study by Careys team in the same issue of Science.

The findings could mean the individual will develop the condition later in life or not, Carey says. Other variants in her genome might mitigate the risk, he says.

We generally look at one gene at a time, but we have about 20,000 genes and they all work in concert, Carey says. Were not sophisticated enough yet to be able to tease out all the genetic interactions, but we know that they exist.

Last year, another team of researchers used the MyCode data to show that genetic changes tied to autism also crop up in many people without the condition. At the 2016 American Society of Human Genetics annual meeting in Vancouver, Canada, last year, they presented results showing that about 2,000 of the MyCode participants carry large deletions or duplications of genetic material associated with autism, intellectual disability or schizophrenia. But less than 5 percent of this group has received treatment for any of the conditions.

The finding suggests that genetic variants can confer features so subtle that they go unrecognized well into adulthood. Researchers could study this group to understand the mildest end of the autism spectrum.

This cohort could help us describe the full picture of autism, the breadth of the phenotype, says Christa Lese Martin, director of the Autism and Developmental Medicine Institute at Geisinger Health System in Lewisburg, Pennsylvania. Martin was a lead investigator on the autism study but was not involved in the new work.

About 125,000 people have enrolled in MyCode so far. By early next year, researchers expect to have sequencing data for 90,000 of the individuals.

See more here:
Many people with harmful genetic variants show no ill effects - Spectrum

OCD-like behavior linked to genetic mutation Science Daily "I believe our study, which found that a mouse with targeted mutations in these genes exhibited OCD-like behaviors, helps support the current genetic studies on neuropsychiatric and neurodevelopmental disorders in humans." The traits of OCD the mice in ... and more »

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OCD-like behavior linked to genetic mutation - Science Daily

Fibrocell Announces Dosing of First Patient in Phase I/II Clinical Trial of FCX-007 Gene Therapy for Treatment of ... P&T Community Fibrocell is an autologous cell and gene therapy company translating personalized biologics into medical breakthroughs for diseases affecting the skin and connective tissue. Fibrocell's most advanced product candidate, FCX-007, has begun a Phase I/II ... and more »

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Fibrocell Announces Dosing of First Patient in Phase I/II Clinical Trial of FCX-007 Gene Therapy for Treatment of ... - P&T Community

CRISPR-Cas9 can be delivered directly into the eyes of mice and treat age-related macular degeneration efficiently and safely.

Asian Scientist Newsroom | February 22, 2017 | In the Lab

AsianScientist (Feb. 22, 2017) - South Korean researchers have used CRISPR-Cas9 gene editing to treat symptoms of age-related macular degeneration (AMD) in mice. Their findings have been published in Genome Research.

It is estimated that almost one in every ten people over 65 has some signs of AMD, and its prevalence is likely to increase as a consequence of the aging population. AMD is a form of blindness which causes distorted vision and blind spots.

AMD in older adults and retinopathy of prematurity in newborns are the leading cause of blindness in those respective age groups. In both diseases, abnormally high levels of vascular endothelial growth factor (VEGF) are secreted. In AMD, VEGF causes the formation of new blood vessels in the eyes but also leads to leakages of blood and fluid into the eye, damaging an area at the center of the retina called macula.

Injections of anti-VEGF drugs are the most common treatment for AMD, but at least seven injections per year are required because VEGF is continuously overexpressed by the cells of the diseased retinal pigment epithelium. Instead of such invasive treatments, scientists at the Institute for Basic Science (IBS) believe that gene therapy with the third generation gene editing tool CRISPR-Cas9 could improve the situation.

The injections tackle the effects, but not the main cause of the problem. By editing the VEGF gene, we can achieve a longer-term cure, explained Professor Kim Jin-Soo, Director of the Center for Genome Engineering at IBS.

CRISPR-Cas9 can precisely cut and correct DNA at the desired site in the genome. The CRISPR-Cas9 system works by cutting DNA at a target site, in this case, inside the VEGF gene. Two year ago, IBS scientists proved that a pre-assembled version of CRISPR-Cas9 called Cas9 ribonucleoprotein (RNP) can be delivered to cells and stem cells to modify target genes.

The pre-assembled complex works rapidly and degrades before the body has time to build up an immune response against it. Despite these advantages and previous successes, the difficulty in delivering pre-assembled CRISPR-Cas9 has limited its use in therapeutic applications.

In this study, the research team successfully injected CRISPR-Cas9 into the eyes of a mouse model with wet AMD and locally modified the VEGF gene. Initially, they found that the delivery of the pre-assembled CRISPR-Cas9 complex is more efficient that the delivery of the same components in a plasmid form.

Secondly, the complex disappeared after just 72 hours. Scientists assessed the whole genome of the animals and found the CRISPR-Cas9 complex modified only the VEGF gene and did not affect other genes. The progression of the eye disease was monitored by looking at choroidal neovascularization (CNV), the creation of new blood vessels between the retina and the sclera, a common problem of wet macular degeneration.

The researchers found that the CRISPR-Cas9 complex reduced the CNV area by 58 percent. Moreover, cone dysfunction, a likely side effect that takes only that days to show in mice, did not occur a week after the treatment.

We have developed a treatment to suppress CNV by inactivating the VEGF gene, one of the causes of AMD. We envision that, in the future, surgeons will be able to cut and paste disease-causing genetic elements in patients, explained Kim.

While CRISPR-Cas9 is conventionally used to correct mutations causing hereditary diseases or cancer, this study suggests a new therapy for non-hereditary degenerative disease.

We believe that this is a new therapeutic modality for the treatment of non-hereditary degenerative diseases, said study co-author Professor Kim Jeong Hun from Seoul National University. We confirmed the effect on the animal models of the disease and now we wish to continue with preclinical trials.

The article can be found at: Kim et al. (2017) Genome Surgery Using Cas9 Ribonucleoproteins for the Treatment of Age-related Macular Degeneration.

Source: Institute for Basic Science. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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Editing Away AMD With CRISPR - Asian Scientist Magazine

For decades, some unluckydog lovers have welcomeda bundle of barking joy into their homes, only to see them perish from a mysterious disease mere weeks after their birth. The pups seemingly healthy muscles had literally wasted away in front of their owners eyes until they could no longer stand and breathe.

It wasnt until 2010 that a French research team isolated the genetic cause of this specific muscle-wasting disease in a group of Labrador Retrievers; these dogs were suffering from a single mutation that left them unable to produce an essential protein known asmyotubularin.Whats more, it was the exact kind of mutation and disease also long found in male human babies, too. That made the researchers wonder if these unfortunate puppiescould help us study the disease and even someday find a way to saveboth pets and people.

Now, years down the road, it appearsthey were right, thanks to a cutting-edgegene therapy treatment.

An international group of researchers, including some from the original French team, gathered together 10-week-old puppies with the mutation to take part in a randomized controlled trial. The dogs who were given a treatment that repaired their defectivemyotubularingene avoided the crippling muscle degeneration that killed the placebo-treated dogs by week 17. And by the ninth month of study, the saved puppies muscle and neurological function continued to match readings from healthy dogs, particularly forthose that got the highest doses.

The findings, building on an earlier proof-of-concept study of dogs and mice by the researchers, signal that a scaled-up treatment could save the lives of boys with the same sort of genetic flaw.

I believe that the dog study will be about as close as we will ever get to a human study, senior author Dr. Martin Childers of the University of Washington told Vocativ in an email. Because we found evidence that the gene therapy product spread throughout the entire skeletal musculature of adult dogs after a single infusion, it seems reasonable to expect a similar result in human patients.

Gene therapy has received plenty of attention for its potential to treat otherwise irreparable DNA defects, but according to the researchers, theres been little focus on bone- and muscle-relatedgenetic disorders. The condition treated in the current study, called x-linked myotubular myopathy, affects around one in every 50,000 boys, with most sufferers living no more than a few years. And though theres no true tally of how often it affects dogs, case reports of similar-sounding diseases have been published stretching back decades.

There will undoubtedly be hurdles to climb before the treatment Childers and his team developed, or a similar one, can be tested in people, Childers said. It is always possible that humans might respond differently, thus, clinical trials will be conducted with extraordinary care and oversight, he explained. And though the dogs suffered little adverse effects from the therapy delivered via a harmless virus researchers will still have to watch out for any possible toxicity in people.

That said, the treatment offers hope for both man and mutts. The changes seen after a single treatment have lasted for several years in the small sample of dogs the team has raised. So its possible that people wont need repeated doses or they would be infrequent, Childers said a big positive, given how expensive gene therapy is today.

And its also likely that these treatments, within the larger field of regenerative medicine, will find a place for dogs and other animals sooner than it will for people.

Veterinary medicine is ahead of human medicine in some cases with respect to regenerative technologies, Childers said. Stem cell infusions, for example, have been given to pets and horses for more than a decade.

But people may not have to wait so long for the promise of gene therapy either. Childers is hopeful that Audentes Therapeutics, a San Francisco biomedical company hes collaborating with (and which partially funded the current study), will begin their first human trials of a gene therapy treatment for x-linked myotubular myopathy, based on his teams research, later this year.

The teams findings were published earlier this February in Molecular Therapy.

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Gene Therapy Saves Puppies From A Fatal DiseaseAnd Maybe Us Next - Vocativ