CVM Faculty Members to Promote Canine Health with New Research Grants

Story by Megan Myers

Drs. Nick and Unity Jeffery, a husband-and-wife duo at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), have received canine health research grants from the American Kennel Club’s (AKC) Canine Health Foundation (CHF).

Dr. Unity Jeffery
Dr. Unity Jeffery

In celebration of its 25th anniversary, the AKC CHF awarded more than $2.1 million in 36 new canine health research grants in February. The selected projects were chosen based on their ability to meet the highest scientific standards and to have the greatest potential to advance the health of all dogs.

In her Dogs Helping Dogs Laboratory, Unity Jeffery, an assistant professor in the CVM’s Department of Veterinary Pathobiology (VTPB), will conduct research for her grant “Tumor-educated Platelets: A Minimally Invasive Liquid Biopsy for Early Cancer Diagnosis.”

Studies in human medicine have shown that RNA in blood platelets is a promising marker for various types of cancer.

Unity Jeffery’s study, in collaboration with Drs. Emma Warry, Jonathan Lidbury, and Chris Dolan, from the CVM’s Department of Small Animal Clinical Sciences (VSCS), will act as a proof of principle to determine if this information is translational into canine medicine.

If so, her research may be the first step in developing a blood-based screening test or liquid biopsy for canine cancer.

“One of the big problems with cancer in dogs is that because dogs can’t talk, they can’t let us know when they’re starting to feel just a little bit unwell or show very mild symptoms,” she said. “That means that we often don’t diagnose cancer in dogs until very late, when the cancer’s already widespread throughout the body.”

By using a test that can detect cancer earlier, veterinarians may be able to use more targeted treatment protocols that have reduced side effects.

“The hope of early diagnosis is that maybe that’s your chance to fully eliminate the cancer rather than just prolong life,” she said.

Dr. Nick Jeffery
Dr. Nick Jeffery

Meanwhile, CVM professor and neurologist Nick Jeffery will be working to extend results from a previous research project for his grant “Clinical Trial of Prevotella histicola Supplementation to Ameliorate Meningoencephalomyelitis of Unknown Origin (MUO).”

In a previous project, Nick Jeffery found that dogs with MUO, a disease of the central nervous system that resembles multiple sclerosis in humans, have an unusual balance of bacteria in their guts. Particularly, one bacteria that is known for controlling inflammation was consistently at lower levels.

His project will focus on providing supplements of that reduced bacteria to dogs with MUO to hopefully improve the disease’s outcome.

“We’re going to culture the bacteria and then put them into capsules that dogs can take every day,” he said. “The idea is that it will help us get better control of the disease, which is quite serious and quite a lot of dogs will die of it. We’re hoping that by supplementing with this bacteria, we might improve their survival.”

In addition to improving the survival of dogs with MUO, the bacterial supplement could also provide a way to reduce the use of immunosuppressive drugs, improving the dogs’ overall health and wellbeing.

Similar to the translational aspect of Unity Jeffery’s project, Nick’s may also one day play a role in human medicine by suggesting a new treatment method for multiple sclerosis.

“I was very pleased to get the grant, especially since it was a follow up on a previous study,” he said. “It’s fantastic to try out bacterial supplementation. This sort of approach is pretty new in all medicine, so it’s a great opportunity to test the idea and also try to fix dogs that have got a very serious condition.”

“I’m very grateful to the AKC Canine Health Foundation and the owners and breeders who donate to the charity,” Unity Jeffery said. “My Dogs Helping Dogs Lab, where we use canine patients and healthy volunteers to try to better diagnose and treat common canine diseases, fits really nicely with the AKC’s mission to improve the health of both pedigree dogs and the whole canine population. It’s a charity that I feel very honored to be funded by and very grateful for their continuing support.

“Nick and I have pet dogs at home and we love our dogs; they’re our family,” she said. “For me, I feel that I do the same type of research for my patients as a human doctor would do for theirs, and that’s what’s great about working in a veterinary school and having the opportunity to obtain funding from sources like the AKC.”

About the AKC CHF

Since 1995, the AKC Canine Health Foundation has leveraged the power of science to address the health needs of all dogs. With more than $56 million in funding to date, the Foundation provides grants for the highest quality canine health research and shares information on the discoveries that help prevent, treat and cure canine diseases. The Foundation meets and exceeds industry standards for fiscal responsibility, as demonstrated by their highest four-star Charity Navigator rating and GuideStar Platinum Seal of Transparency. Learn more at www.akcchf.org.

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216

CVM Researcher to Study Tick Vaccines in Brazil as Fulbright Recipient

Dr. Albert Mulenga in his lab
Dr. Albert Mulenga

Story by Margaret Preigh

Dr. Albert Mulenga, a professor in the Texas A&M College of Veterinary Medicine & Biomedical Sciences’ (CVM) Department of Veterinary Pathobiology (VTPB), will spend four months continuing his research on tick vaccines in Brazil thanks to a Fulbright award.

The prestigious award will support Mulenga’s research abroad, during which he will work alongside researchers in Porto Alegre, Brazil, at the University Rio Grande do Sul. In addition to his research, Mulenga will teach a course and advise a Brazilian graduate student who will be helping him conduct his research on tick vaccines.

Under the Fulbright Program, Mulenga is tasked with “increasing mutual understanding between the people of the United States and the people of other countries,” according to the J. William Fulbright Foreign Scholarship Board.

This directive ties in closely to what Mulenga, as an immigrant, feels his career represents.

“I represent what is possible in the United States,” he said. “When I came to this country, I started my career as a postdoctoral fellow, and now I’ve risen all the way to a professor and associate head of a department. Once you put your mind to it, you can achieve what you want.”

The Fulbright program is the largest and most diverse international exchange program; recipients are carefully selected on the basis of their leadership and contributions to society under the supervision of a 12-member presidentially appointed board.

Alumni of the program include 60 Nobel Laureates, 86 Pulitzer Prize winners, 74 MacArthur Fellows, and countless other bright and influential members of society.

Mulenga is both honored and humbled to join their ranks.

“These former recipients have gone into leadership positions, have done amazing things after the Fulbright,” he said. “The people who have gone through this program have benefited. I want to make sure that I take advantage of those opportunities.”

Dr. Ramesh Vemulapalli, Professor and Department Head of VTPB at the CVM, recommended Mulenga for the award and believes that Mulenga will find his place among previous recipients.

“Dr. Mulenga’s scholarly accomplishments are a result of his scientific creativity, tenacity, and hard work,” Vemulapalli said. “He represents the best of American values. We are very proud that he is recognized as a Fulbright Scholar.”

Mulenga’s research will be instrumental in improving cattle health in Brazil and the United States, the two leading beef producers globally. According to the Organization for Economic Co-operation and Development (OECD), global consumption of beef is 14.5 kg per person each year. As developing countries continue to grow economically, global meat consumption is expected to increase.

“Brazil’s cattle industry is huge,” Mulenga said. “Ticks and tick-borne disease are a very big impediment, so they are trying to find solutions. Coming from Texas, it’s a win-win. If I’m successful in this project, the data could be directly applicable here.”

Currently, Mulenga is conducting research to develop a vaccine against cattle fever ticks under Kleberg Foundation support. This builds on his National Institutes of Health-funded research to understand how the Lonestar tick and the blacklegged tick transmit human tick-borne diseases. He believes that insight gained from his Fulbright project in Brazil will also translate to this ongoing study.

The new vein of research Mulenga will undertake in Brazil will investigate a novel way to empirically evaluate antigens for new tick vaccines. Current vaccine development models involve first selecting an antigen, then building a vaccine off of that molecule.

His research in Brazil will be unique in that he will be allowed to work in much closer proximity to these ticks than United States regulations would allow.

“There is a big benefit because, in Brazil, I can directly observe cattle fever parasites,” he said. “My collaborator in Brazil is allowed to work with infected ticks; I’m not allowed. With uninfected or infected ticks, we are restricted to working in a quarantine zone between the border of Texas and Mexico.”

Though Mulenga’s research and work as an ambassador will build off of his previous experiences, he looks forward to combining his strengths in research and communication to act as an academic representative of our country.

“At a scientific meeting, I’m just focused on my research,” he said. “Under this program, I also have to communicate the values that allowed me to come to this country and become a member of this society, do my work, and be able to get this award.”

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216

A Canine Connection

Through her Dogs Helping Dogs laboratory, Dr. Unity Jeffery studies common canine diseases to improve veterinary care in the future.

Story by Dr. Ann Kellett

 

Dr. Unity Jeffery in her lab
Dr. Unity Jeffery

If you ask for Dr. Jeffery at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), you’ll need to be more specific. Dr. Nick Jeffery and Dr. Unity Jeffery are a husband-and-wife team who both devote their lives to advancing animal health care at the CVM.

An assistant professor of veterinary pathobiology, Unity Jeffery utilizes her Dogs Helping Dogs laboratory to better understand, diagnose, and treat common canine diseases.

She got the idea while earning her Ph.D. at Iowa State University.

“To get research funding, small animal veterinarians typically have to focus on problems that overlap with human medicine,” she said. “Dogs Helping Dogs focuses on problems that aren’t so interesting to funding agencies.”

TACKLING THE MOST IMPORTANT PROBLEMS 

At the moment, she’s working on some of the biggest problems a dog can have—heatstroke and a disease associated with it (and other conditions), called disseminated intravascular coagulation (DIC).

Heatstroke can occur quickly and is deadly in the majority of cases. It is of particular concern for dogs with thick fur and short noses, as well as those that are obese or have other medical conditions.

DIC is less well known to most dog lovers and occurs when numerous small blood clots form throughout the body in conjunction with a severe illness such as cancer, sepsis, and liver or kidney disease.

About 150 dogs have provided blood for her studies so far. Healthy dogs, mostly the pets of staff and students at the CVM, provide control samples, and others come from dogs that have been treated at the Small Animal Hospital (SAH).

“The patients we work with today are teaching us how to improve future care,” Jeffery said. “I am very grateful for the generosity of the owners and pets who participate in our studies and the technicians, interns, residents, and clinicians who help make this possible.”

Gathering data in these kinds of clinical studies takes much longer than in traditional experimental research, but Jeffery says the enrollment target for two studies was reached in June.

“I’m really excited to see the final results,” she said. “With one study, we’re hoping to take a first step in developing new tests and therapies for dogs affected by heatstroke. The other looks at how different fluid therapies affect the health of blood vessels, which we hope will help us keep patients from developing DIC.”

Dr. Unity Jeffery working in her lab
Dr. Unity Jeffery

ASSESSING LABORATORY ACCURACY

Jeffery’s other main focus is to improve the accuracy of the tests given by veterinarians during an examination and the laboratory results of these tests.

“Laboratory and point-of-care analyzers can be marketed to veterinarians even though they may not consistently provide accurate results,” she said. “Laboratory accuracy is important to us because it is a major patient safety issue and we base so many of our diagnostic and treatment decisions on laboratory testing.”

Several projects are underway or recently completed. In one, she and CVM emergency and critical care team member Dr. Christine Rutter worked with a couple of point-of-care instrument manufacturers to assess the performance of their analyzers in clinical patients. In another, she and clinical pathology resident Carolina Azevedo looked at how high blood lipid concentrations interfere with lab testing.

“One of the projects that I’m most excited about is a study involving data from the Morris Animal Foundation’s Golden Retriever Lifetime Project,” Jeffery said. “We’re using annual health check data from the dogs enrolled in this study to determine how much lab results vary in healthy dogs. The results will help us determine if changes detected at annual wellness checks are clinically important or just normal fluctuations.”

Jeffery expects some of these studies to have an immediate impact.

“I hope our fluid therapy study will help improve the standard of care of canine patients almost immediately after it is published,” she said. “Others, like the heatstroke study, are chipping away at a really big problem. It will probably be a few years before it pays off, but without these initial studies we’ll never improve survival for these patients.”

Her colleagues understand the importance of this work.

“I’ve got great collaborators in the Small Animal Hospital who take the time to enroll patients and collect samples, even when their day-to-day clinical work is very demanding,” she said. “This is particularly true of our emergency and critical care service. They deal with the most seriously ill patients in the hospital but they recognize that clinical research holds the key to improving care for their patients.”

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Note: This story originally appeared in the Fall 2019 edition of CVM Today.

For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216

Feeling the Heat

Dr. Deb Zoran uses her work with Texas A&M Task Force urban search and rescue dogs to study how different breeds have unique temperature ranges and how that impacts their ability to save lives.

Feeling the Heat

Texas A&M, Cornell Collaborate to Advance Education Research, Expand Pipeline for Underrepresented Students

Texas A&M and Cornell universities have joined forces to advance research on antimicrobial resistance (AMR) in veterinary medical education and to expand the pipeline for underrepresented students in the field.

Funded by a $300,000 federal grant from the United States Department of Agriculture’s (USDA) National Institute of Food and Agriculture (NIFA), researchers from both universities will work together to develop and study the impact of a comprehensive collection of competency-based educational resources on antimicrobial resistance to aid veterinary education programs throughout the United States.

The three-year grant will finance research focused on the development of multidisciplinary, problem-based lessons on antimicrobial resistance, the creation of an online platform to share educational resources with all veterinary colleges in the U.S., and expanding the pipeline for underrepresented student populations regarding career opportunities in food and agricultural sciences, veterinary medicine, and public health.

“Antimicrobial resistance poses an increasingly serious threat to global health, and veterinarians must be properly equipped to assume leadership roles in addressing this challenge,” said Dr. Kevin Cummings, principal investigator for Cornell University. “Crucial to the success of the AMR mitigation effort is the need to educate a wide variety of stakeholders about proper antimicrobial stewardship in production agriculture.”

Nicola Ritter, principal investigator for Texas A&M University and director of the Center for Educational Technologies (CET), housed in Texas A&M’s College of Veterinary Medicine & Biomedical Sciences (CVM), will lead efforts to create the online platform and implement the outreach campaign. The CET will share the lessons created from this project with all U.S. veterinary colleges on an open, online platform.

As a part of the outreach campaign, the Texas A&M team also will share lessons on antimicrobial-resistance topics suitable for undergraduate audiences to four universities within the Texas A&M System that have significant under-represented student populations, including Prairie View A&M University, West Texas A&M University, Texas A&M Kingsville, and Tarleton State University.

“The undergraduate outreach campaign dovetails well with Texas A&M’s initiative to expand veterinary education, research, and outreach into several rural areas of Texas with under-represented student populations,” said Ritter, who is also an instructional assistant professor in the CVM’s Department of Veterinary Integrative Biosciences (VIBS).

In addition to researchers from Cornell University, the multi-institutional project also includes researchers from Texas A&M’s CVM and College of Education & Human Development.

“These groups understand that it will take multidisciplinary teams to achieve the institution’s goals of transforming education within the Texas A&M University System and around the world,” Ritter said.

The team also links together other female leaders in the field of veterinary medicine education, including:

By the end of the project, the team anticipates reaching 3,000 graduates per year from veterinary colleges across the United States and 1,000 undergraduates per year from programs related to animal science.

 

About Texas A&M University College of Veterinary Medicine & Biomedical Sciences

The Texas A&M College of Veterinary Medicine & Biomedical Sciences was established nearly a century ago to serve the needs of the Texas livestock industry.  Today it serves the largest livestock industry in the U.S., in addition to protecting the health of all animals, people, and the environment in the country’s second-most populous state. It is an innovative leader in veterinary medical education recognized for housing the Center for Educational Technologies and graduating top-quality, practice-ready veterinarians from Texas A&M University, which is the seventh largest university in the nation and a top 20 Tier One research institution.

About Cornell University College of Veterinary Medicine

Cornell University’s College of Veterinary Medicine is recognized internationally as a leader in public health, biomedical research, animal medicine, and veterinary medical education. Ranked the No. 1 veterinary college in the nation by U.S. News & World Report consistently since 2000, the college’s strength is due to the strategic breadth and depth of its programs, to the expertise of its faculty, and to the achievements of its alumni. Cornell awarded the first veterinary degree in the United States to Daniel Salmon, best known for discovering Salmonella, and again made history in 1910 when it awarded the first American woman with a veterinary degree.

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Megan Palsa, Executive Director of Communications, Media & Public Relations, Texas A&M College of Veterinary Medicine & Biomedical Science; mpalsa@cvm.tamu.edu; 979-862-4216; 979-421-3121 (cell)

Texas A&M Study Links Breast Cancer, Body’s Internal Clock

Weston PorterFor years, doctors have associated the BRCA1 and BRCA2 gene mutations with an increased risk of breast cancer.

But researchers at Texas A&M University have now identified another gene that may have an impact on breast cancer—associated with the body’s circadian rhythm.

Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM) professor Weston Porter and his team have found that Period 2 (Per2), a regulatory mechanism within each cell’s peripheral clock, plays a crucial function in mammalian mammary gland development and that when suppressed, Per2 leads to severely disrupted gland development in mice.

The findings, published in the scientific journal Development, add to a growing list that ties disruptions to our circadian rhythm—that is, the “central clock” mechanism in our brains—to a higher risk of cancer progression, obesity, some neuromuscular diseases, and other impairments, including jetlag.

Circadian rhythm is controlled by the suprachiasmatic nucleus (SCN) in the brain’s anterior hypothalamus. In addition to coordinating our sleep patterns, the SCN coordinates the other peripheral clocks in our body, which run on a 24-hour cycle that corresponds with each day.

“Not only do we have a central clock, but every one of our cells has one of these peripheral clocks and they’re in coordination with the central clock,” Porter said. “When you wake up in the morning and see light, the light goes right into the brain and it triggers this molecular mechanism that regulates the (circadian rhythm) process.”

In their study, Porter’s team evaluated Per2, which provides the “negative feedback,” or counterbalance, to the circadian rhythm process.

“The negative and positive feedback mechanisms are constantly in balance, going up and down. One’s up during the day, the other one’s up at night—they oscillate right at 24 hours—but when you see light, that resets it in the morning,” Porter said. “WhenPer2 comes back, it suppresses another gene called BMAL or CLOCK.”

Their finding—that Per2 has a crucial function outside of timekeeping in mammalian mammary gland development where Per2plays a role in cell differentiation and identity—describes a potentially important role for Per2 in breast cancer. Per2 expression is lost in a large percentage of mammary tumors, which suggests it may have protective effects.

“We discovered that these glands have what we call a kind of a bipotent phenotype; they’re actually halfway to cancer,” Porter said. “They’ve already have many of the characteristics you would see in a premalignant cell.

“We started to look at the mechanism associated with that and found that the stem cell markers associated with a loss of Per2are more basal, which is characteristic of more invasive cancer,” he said. “This reinforces the idea that Per2 is functioning as a tumor suppressor gene associated with cell identity.”

In addition to disruption of the developing mammary gland, Porter also saw the same defect in transplant studies, showing that it is Per2, and not just the central clock itself, that is responsible for the lack of mammary ductal growth in the developing gland.

Their next step is to revisit studies that correlate working a night shift with an increased risk of breast cancer.

“Right now, we are investigating how our findings relate to humans,” Porter said. “There are studies out there showing a relationship between decreased levels of Per2 and certain types of breast cancer, which are more invasive. So, we believe that there is a direct relationship.”

Understanding circadian rhythm and its effects on the body have become increasingly important to the science community. The 2017 Nobel Prize for Physiology or Medicine was awarded to researchers for discoveries of the molecular mechanisms controlling the circadian rhythm, and the National Cancer Institute recently named the role of circadian rhythms in cancer as one of their 12 provocative questions for the year.

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Megan Palsa, Executive Director of Communications, Media & Public Relations, Texas A&M College of Veterinary Medicine & Biomedical Science; mpalsa@cvm.tamu.edu; 979-862-4216; 979-421-3121 (cell)

Texas A&M Study Offers New Virus-Host Protein Insight, New Possibilities for Antiviral Development

Viruses have a very limited set of genes and, therefore, must use the cellular machineries of their hosts for most parts of their growth.

Leif Andersson
Leif Andersson

In a new study, scientists at Texas A&M and Uppsala universities have discovered a specific host protein that many viruses use for their transport within the cell.

The human gene, ZC3H11A, is found in all vertebrates and is expressed essentially in all human cells; the gene has been known for about 20 years, but its functional importance has been unknown.

The team, led by Texas A&M professor Leif Andersson, however, has discovered that ZC3H11A is critical for the replication of multiple medically important viruses—including adenovirus, influenza virus, HIV, and herpes simplex virus—which opens up new possibilities for the development of new broad-spectrum antiviral therapies.

The discovery was published April 2 in the Proceedings of the National Academy of Sciences (USA).

With modern DNA sequencing technologies, it is relatively easy to identify all genes coding for proteins in an organism, but it is often much more challenging to really understand the cellular function of proteins, according Andersson, professor of animal genomics in the Texas A&M College of Veterinary Medicine & Biomedical Sciences’ (CVM) Department of Veterinary Integrative Biosciences (VIBS) and professor of functional genomics at Sweden’s Uppsala University.

The discovery is the result of a project by Uppsala doctoral student Shady Younis, who used the gene-editing tool CRISPR-Cas9 to inactivate the ZC3H11A gene in a human cell line; initially, he found that the inactivation of ZC3H11A had little effect, showing that it is not essential for the growth of these human cells.

But while discussing his finding with fellow doctoral student Wael Kamel, Younis decided to challenge the cells lacking ZC3H11A with a virus infection.

The ZC3H11A protein (in green) surrounds the adenovirus replication centers in human in HeLa cells.
The ZC3H11A protein (in green) surrounds the adenovirus replication centers in human in HeLa cells. Photo by Shady Younis

To their surprise, there was a drastic reduction of the growth of adenovirus (a group of viruses that can infect the tissue linings of the respiratory tract, eyes, intestines, urinary tract, and nervous system) in the cells lacking ZC3H11A, compared with cells expressing the protein.

The team has now demonstrated that at least four different viruses that replicate in the host cell nucleus are dependent on the ZC3H11A protein for their efficient growth; these viruses need ZC3H11A for the transport of virus RNA from the nucleus to the cytoplasm, where the virus proteins will be produced before the viruses can exit the cell and infect other cells, Kamel said.

“This serendipitous discovery is an excellent example of how a good scientific environment can inspire scientists to collaborative efforts that may lead to important scientific discoveries,” Andersson said.

The group also has demonstrated that ZC3H11A is a stress-induced RNA binding protein and appears to be part of a previously unknown mechanism for how cells handle stress.

The observation that the amount of ZC3H11A protein increases during a virus infection was a very surprising finding since viruses typically shut down host-cell protein expression to favor virus production, Andersson said.

“Our data suggest that nuclear-replicating viruses have hijacked a cellular mechanism for RNA transport activated during stress for their own advantage,” he said.

The spread of the influenza virus that has severely impacted people around the world proves there is a strong need to develop new antiviral drugs; a major goal for the team is now to test if they can block how viruses take advantage of the function of the ZC3H11A protein and if this will impair virus growth in living animals, not only in cells as they have proven in the current study, Andersson said.

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Megan Palsa, Executive Director of Communications, Media & Public Relations, Texas A&M College of Veterinary Medicine & Biomedical Science; mpalsa@cvm.tamu.edu; 979-862-4216; 979-421-3121 (cell)

A&M Research Receives FDA Orphan-Drug Designation for Angelman Syndrome Treatment

College Station, Texas — The U.S. Food and Drug Administration has granted orphan-drug designation to GTX-101 for the treatment of Angelman syndrome, a rare

Scott Dindot
Scott Dindot

neurogenetic disorder that affects approximately 1 in 15,000 people. GTX-101 is the first drug candidate for startup GeneTx Biotherapeutics, LLC (GeneTx).

“No approved treatments for Angelman syndrome exist today,” said Allyson Berent, GeneTx chief science officer. “The FDA’s orphan-drug designation for GTX-101 highlights the significant need for treatments for individuals with Angelman syndrome, and we believe that targeted delivery of GTX-101 represents a promising, novel approach to treat this devastating disorder.”

Angelman syndrome (AS) is caused by a loss of function of the maternally inherited UBE3A gene. Symptoms of AS include developmental delay, impaired motor function, loss of speech and epilepsy.

GTX-101 is an investigational antisense oligonucleotide designed to inhibit transcription of the UBE3A-AS across the paternal allele of UBE3A. In vitro studies show that as a result of this inhibition, transcription of the paternal UBE3A gene is restored in neurons of the central nervous system.

An antisense oligonucleotide is a synthetic string of nucleic acids that interferes with the normal processing of a target gene to, for example, turn on or turn off expression of a target gene or to alter the splicing pattern of the gene. Clinical trials have shown promising results using antisense oligonucleotides to treat neurogenetic disorders for spinal muscular atrophy and amyotrophic lateral sclerosis.

“This is a new area of medicine, known as a targeted therapy,” said Scott Dindot, Ph.D., associate professor in the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM). “Historically, clinicians have treated symptoms of a disease or disorder with medication but not the cause of the condition. A targeted therapy goes after the cause of the condition and attempts to fix it.”

GeneTx entered into a worldwide license agreement with The Texas A&M University System and a research collaboration agreement with Texas A&M AgriLife Research, under which GeneTx hopes to further develop and commercialize this novel antisense oligonucleotide as a targeted therapy for patients with the disorder.

“The FDA’s orphan drug designation for GTX-101 is an important next step in bringing effective treatments to individuals with Angelman syndrome,” said Paula Evans, GeneTx chief executive officer. “Activation of the normally silent paternal UBE3A gene has the potential to mitigate many of the disorder’s debilitating symptoms.”

The Orphan Drug Act became law in 1983. Fewer than 5,000 applicants have received this special designation, according to the FDA website. Rare conditions are often described as orphan diseases or disorders when there are few or no treatment options. There are about 7,000 known orphan diseases in the United States.

The FDA’s Orphan Drug Designation program provides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases, or disorders that affect fewer than 200,000 people in the United States.

The designation allows the sponsor of the drug to be eligible for various incentives, including a seven-year period of U.S. marketing exclusivity upon regulatory approval of the drug, as well as tax credits for clinical research costs, annual grant funding, clinical trial design assistance, and the waiver of Prescription Drug User Fee Act (PDUFA) filing fees.

About GeneTx Biotherapeutics

GeneTx Biotherapeutics, LLC, is a start-up company dedicated to developing and commercializing safe and effective therapeutics for the treatment of Angelman syndrome.

About Angelman Syndrome

Angelman syndrome (AS) is a rare, neurogenetic disorder caused by a loss of function of the maternally inherited UBE3A gene on the 15th chromosome. UBE3A is an imprinted gene where only the maternal copy is expressed in neurons of the central nervous system. Imprinting of UBE3A is regulated by expression of the paternally expressed UBE3A antisense transcript (UBE3A-AS). Individuals with Angelman syndrome generally have developmental delay, balance issues, motor impairment and debilitating seizures. Some people with AS never walk. Most do not speak. Anxiety and disturbed sleep can be serious challenges among those with AS. While individuals with AS have a normal lifespan, they require continuous care and are unable to live independently. Typical characteristics of AS are not usually evident at birth. Individuals with AS have feeding difficulties as infants and noticeable delayed development around 6-12 months of age. They need intensive therapies to help develop functional skills. In most cases, AS isn’t genetically inherited. Angelman syndrome affects all races and genders. It is often misdiagnosed as autism or cerebral palsy. There is an unmet clinical need for individuals with AS in the areas of motor functioning, communication, behavior and sleep. For more information about Angelman syndrome, please visit CureAngelman.org.

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Megan Palsa, Executive Director of Communications, Media & Public Relations, Texas A&M College of Veterinary Medicine & Biomedical Science; mpalsa@cvm.tamu.edu; 979-862-4216; 979-421-3121 (cell)

Muscular Dystrophy Research

DMD is a devastating disease that affects both children and dogs. It is a genetic disease that affects boys, all of whom die early in life, living only into their twenties, but only after much suffering. Any parent with an affected child is acutely aware of how devastating this disease is, not only to the affected children but also to their families.

The dogs with DMD at Texas A&M are treated with great care and tenderness, as they help unravel the mysteries and potential cures for this dreadful disease. Not only do our people who work with these dogs truly care about them as individuals, the work being conducted is highly regulated and there is rigorous oversight of their care by a number of organizations, including:

  • USDA (United States Department of Agriculture)
  • NIH (National Institutes of Health)
  • DOD (Department of Defense)
  • AAALAC (Accrediting body that comes around every 3 years)

It saddens us that without full knowledge—of what we are doing, how the dogs are treated, and how close we are to an effective treatment—groups have taken a rigid position and are using slander that adversely affects the opinion of those who don’t know all of the facts.

Please be assured that those who work with our dogs have chosen to devote their lives and careers to the care and well-being of all animals.

Texas A&M’s Chiu Receives Grant Through Gulf Research Program

Weihsueh Chiu, a professor in the Texas A&M College of Veterinary Medicine and Biomedical Sciences’ (CVM) Department of Veterinary Integrative Biosciences (VIBS), has received a $700,000 grant from the National Academies of Sciences, Engineering, and Medicine’s Gulf Research Program (GRP).

Dr. Chiu

Chiu’s project on “Prioritizing Risks from Oil Spills: Supporting Decisions with Read-Across Using 21st Century Exposure and Toxicological Sciences” was one of seven projects from researchers across the country funded through the GRP, the National Academies announced on Jan. 24.

“This project further expands Texas A&M’s commitment to using cutting-edge research and technologies to address the impacts of disasters–in this case, oil spills,” Chiu said. “We are bringing together a world-class, interdisciplinary team that reaches well beyond CVM, including researchers at the Texas A&M School of Public Health and Geochemical & Environmental Research Group, as well as Pacific Northwest National Labs, and the consulting firm Center for Toxicology and Environmental Health.”

For the project, Chiu and his collaborators will use new approaches and technologies in exposure science and toxicology to try to predict the toxicity of substances to which people can be exposed during and after an oil spill.

Because an oil spill can involve a complex mix of interacting substances and environmental factors, which then produces many unknowns that are either difficult or not currently possible to account for, the team will work to address existing limitations and improve assessment and decision-making processes relating to public health risks resulting from oil spills.

“The project will build on and leverage several other recently-initiated projects, including the Texas A&M Superfund Research program and the Institute for Sustainable Communities,” Chiu said. “A key feature of all of these projects is their engagement with local communities and decision-makers involved in disaster response and recovery throughout the research process, so as to accelerate the translation of research into actual practice.”

“This project also will demonstrate the importance of engaging partners like local public health departments in Harris and Galveston Counties to ensure that research is effectively translated into policy and practice to reduce the health impacts of oil spills,” said project collaborator Jennifer Horney, department head and associate professor in the Texas A&M School of Public Health’s Department of Epidemiology & Biostatistics.

The project is one of two funded under the “Improving Risk-Based Evaluations to Support a Public Health Response to the Next Oil Spill” category, for projects focused on improving the information available to decision-makers for evaluating public health risks resulting from oil spills.

“Many decisions relating to public health risks are made following a disaster such as an oil spill,” said Chris Rea, associate program officer for the GRP’s Thriving Communities Initiative. “Risk assessment science inherently involves numerous uncertainties, though, and decisions are limited by what we actually know about potential hazards. The Academies’ report highlighted recent advances that could be used to improve the science behind hazard identification, exposure assessment, and risk characterization, and these two projects are working to apply some of those advances for use in assessing oil spill public health risks.”

The GRP funding competition was specifically geared toward projects that would bring researchers and practitioners together to transfer knowledge and work jointly on efforts that advance both science and its application. All awarded projects were selected after an external peer-review process.

“This funding opportunity is an example of how the Gulf Research Program takes advantage of a core strength of the National Academies – to supply expert consensus on using science to address real-world problems,” said Evonne Tang, the GRP’s director of external funding opportunities. “Two recent reports on topics central to the GRP’s mission were the basis of this grant competition, and the awards direct funding toward efforts that will quickly begin to address the recommendations in those reports.”

The GRP is an independent, science-based program founded in 2013 as part of legal settlements with the companies involved in the 2010 Deepwater Horizon disaster. It seeks to enhance offshore energy system safety and protect human health and the environment by catalyzing advances in science, practice, and capacity to generate long-term benefits for the Gulf of Mexico region and the nation.

The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine. The Academies operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln. For more information, visit national-academies.org.