PROGRESS Celebrating a Cure John Lyons
Winter 2019/2020
Texas Biomed Science Briefs Quantitative Biology Adds Up to New Insights
T
exas Biomed welcomed Dr. Diako Ebrahimi as a new Assistant Professor this past Fall. He will establish his own research program in quantitative biology related to the fields of viral and cancer immunology and also collaborate on research projects with Texas Biomed Faculty. Dr. Ebrahimi’s recruitment is part of the Institute’s 10-year strategic plan to recruit nearly 20 new faculty members and double the size of the Institute. “My goal is to develop a collaborative and crossdisciplinary research program that combines multi-omic quantitative analysis with targeted experimental strategies to identify and answer key questions in the fields of viral and cancer immunity,” Ebrahimi shared. “Currently, large amounts of data are being Assistant Professor Diako generated across disciplines Ebrahimi, Ph.D. to study complex biological processes. However, cross-disciplinary quantitative skills are urgently needed to analyze and interpret these massive datasets and direct future targeted experiments.”
Dr. Daadi said. “With this drug, we hope to develop a therapeutic intervention to enhance the bioenergetics and function of our brain cells and improve the general health and well-being of our aged population.” Aging is the number one risk factor for developing neurodegenerative diseases, cancer, diabetes and cardiovascular disease. Among the key underlying pathological mechanisms behind aging is a gradual deterioration of mitochondria, organelles inside cells in which the biochemical processes of respiration and energy production occur. Over time, aging mitochondria become inefficient and are vulnerable to death. Drugs that enhance mitochondrial health may have beneficial effects on aging. Dr. Daadi used a human induced pluripotent stem cell-based assay (test) to screen for FDA-approved drugs that enhance mitochondria functions. This screen identified promising candidates that will now be tested for their efficacy to improve the neurocognitive health of our aged baboons.
he William and Ella Owens Medical Research Foundation has awarded Texas Biomed Associate Professor Marcel Daadi, Ph.D., with a grant of more than $100,000 to test a promising FDA-approved drug for reversing age-related cognitive decline and memory deficits observed in aged baboons.
“Because the baboons are quite intelligent, skilled and able to interact with a computer-based neuropsychological test similar to the one used in hospitals for humans, we are able to detect age-related cognitive decline and how a drug impacts this,” Dr. Daadi explained. To measure the impact of the drug, researchers will employ interdisciplinary approaches including behavioral neuroscience and multimodal brain imaging in collaboration with the UT Health Research Imaging Institute.
“We are truly excited about this opportunity to use aged baboons in our study because they develop human-like, age-related decline in cognitive and motor performances,”
“We are very honored and grateful that our project was funded by the William and Ella Owens Medical Research Foundation,” Dr. Daadi added.
New Grant Funds Anti-Aging Study
T
2
Considering Cannabinoids
T
Leptin, the “satiety hormone” is made by adipose cells that help to regulate energy balance by inhibiting hunger. Leptin is opposed by the actions of the hormone ghrelin, the “ hunger hormone.”
Researchers Find New Mutation in the Leptin Gene
T
he global obesity epidemic is so far-reaching it now has an overarching name: globesity. Texas Biomed Staff Scientist Raul Bastarrachea, M.D., is part of a team that discovered a new mutation in the gene that regulates the key hormone suppressing hunger called leptin. “We keep learning more and more about the role of fat in normal-weight people,” Bastarrachea said. “By researching what goes wrong when genes don’t code correctly for the production of leptin – a protein produced by fat cells – we are coming closer to answers that could help millions of people with metabolic disorders.” In an article in the journal Genes, Dr. Bastarrachea and his co-investigators examined the case of two sisters in Colombia who started off their lives as normal weight babies but who quickly suffered from childhood-onset severe obesity. What scientists found is that these two women have a mutation in the leptin gene on chromosome 7.
he newest Professor at Texas Biomedical Research Institute, Mahesh Mohan, D.V.M, M.S., Ph.D., is an HIV researcher who focuses on what happens at the subcellular level when a person is infected with the virus that causes AIDS. Recently, he has branched out into studying the use of cannabinoids (a psychoactive component in marijuana) to manage the inflammation that often accompanies an HIV infection. “HIV infection results in chronic inflammation. We are working to identify where the changes occur and try to reverse the problem with new feasible pharmacological approaches,” Mohan said. Professor Mahesh Mohan, While the development of D.V.M., M.S., Ph.D. antiretroviral medications to treat HIV means an infection with the virus is no longer a death sentence, many patients still experience significant health issues. His primary work is to find ways to alleviate the inflammation that creates these medical conditions.
Earlier research has shown that cannabinoids can have an anti-inflammatory effect on infected monkeys when given at a certain dose. Dr. Mohan says compounds for humans may end up being some kind of synthetic drug that targets the same receptor as cannabinoids, without the use of marijuana. “There is so much suffering people undergo because of chronic inflammation created by infectious diseases, noninfectious health conditions and aging,” Dr. Mohan commented. “Ancient people used the marijuana leaves for medical purposes centuries ago. I’m very excited about moving this from nonhuman primates to the clinic.”
More work is needed to figure out how to combat leptin deficiencies on a large scale. The Colombian women are in the queue to take Metreleptin — a synthetic analog of leptin. With obesity now a global problem, scientists around the world are searching for ways to keep the issue from becoming a healthcare burden for years to come. Texas Biomed is playing an important role.
3
Celebrating a Cure John Lyons
J
ohn Lyons does not know how he got hepatitis C. Doctors told him he may have acquired the insidious blood-borne infection during his service in Vietnam or contracted it from a 12-pint blood transfusion following a car wreck in the late 1970s, long before the blood supply was screened for the virus. What John knows is that hep C lurked in his body for years, seriously damaging his liver. “When doctors told me I had elevated liver enzymes, I had no idea what they were talking about,” John remembers. Hep C did not even have a name until 1991. Before then, the virus was simply called non-A, non-B hepatitis. The stealthy virus often does not create symptoms for many people until decades later when it can result in cirrhosis of the liver or liver cancer, earning the disease the nickname “The Silent Killer.”
It is mindboggling to be in the final stages of a terminal illness and then be cured,” John says. “I really think it is critical to our nation that we invest in the future of science for the next generation.” — John Lyons
John’s disease was detected after surgery for another health issue. In 1997, a liver biopsy confirmed what his rising liver enzymes were telling doctors. He had hep C. The standard drug regimen was difficult — shots and pills and blood draws. John’s health started spiraling downward quickly. “The original therapy was onerous,” John explains. “I was achy all the time like I had the flu.” The 6’3” San Antonian dropped from a weight of 215 down to 150 pounds. This strong Air Force veteran was a shadow of his former self. For years, the pills and injections would take his virus load down to undetectable levels. “But,” John says, “I was about to go undetectable. I was weak as a pup,” he recalls. “I was deteriorating physically, emotionally and spiritually.” Doctors placed him on a liver transplant waiting list. Believing he had nothing to lose, John volunteered for a free drug trial at the Texas Liver Institute in San Antonio in 2012. For 24 weeks, he took regular hep C medications and two “mystery drugs” as he called them.
4
John Lyons. Photo right and cover photo by Josh Huskin.
His liver enzymes went down and his viral load dropped from 2 million to 25 in a matter of weeks. “It was jaw dropping,” John recalls.
a crucial role in late-stage testing of this new approach to treating hep C. A single pill a day for 3 months can wipe out this previously intractable health issue.
At the one-year mark, his doctor sent him an official letter declaring he was cured of the infectious disease that had threatened his life. Seven years later, John still has that letter. His name was removed from the transplant waiting list.
Around the world, an estimated 150 million people are chronically infected with hepatitis C and about 700,000 of them die each year from hep C-related liver diseases. Thanks to recent scientific breakthroughs, most patients can now be cured in a matter of a few weeks with these revolutionary new medications.
Scientists at Texas Biomed and nonhuman primates at the Southwest National Primate Research Center played
John is 70 years old now. With a new lease on life, he is pursuing higher education by earning a Master’s degree online through Texas A&M University. He hopes to teach undergraduates when he finishes. It is a future he dared not plan for just a few years ago. “It is mindboggling to be in the final stages of a terminal illness and then be cured,” John says. “I really think it is critical to our nation that we invest in the future of science for the next generation.”
5
Hepatitis C: Texas Biomed’s historical role in creating a cure
T
he outlook for people with chronic hepatitis C virus (HCV) has changed dramatically in recent years. Approximately 2.7 million Americans are infected, and the opioid crisis is rapidly increasing those numbers. Historically, much of the exposure to this virus involved transfusions and other blood products.
One pill a day for 12 weeks cures a disease that has been wreaking havoc in the liver for decades. Chimpanzees were the only animal model that could be infected with HCV. We don’t use chimpanzees for research any longer, but we must appreciate that they were critical for every step of the process in developing this cure.” — Dr. Robert Lanford
6
For more information on the science behind these breakthroughs, visit www.txbiomed.org/inside-the-lab/robert-lanford
Highlighting New Grant Funds Our Anti-Aging Texas Biomed Study Donors
J
ohn Lyons is one of several Texas Biomed advocates sharing their stories of how #ScienceGaveMeAFuture. Our ability to defeat the disease threats of today and tomorrow depend upon more than the expertise of scientists. Success depends on visionary and courageous supporters investing in the health of our global community. Texas Biomed is looking for partners willing and able to connect us with leaders across the world ready to invest in a new, creative solution to the challenges we face with infectious diseases. Winning the many battles ahead against infectious diseases will take warriors in science, advocacy and philanthropy. Join the “Scientific Revolution” today.
Visit www.txbiomed.org/science-gave-me-a-future/
“Our family has always been supporters of Texas Biomed as our primary philanthropy. Recently, their mission hit our family head on as Cappy has battled a throat and neck cancer that had its start as a viral infection, probably acquired years ago. It is our hope that with ours and so many others’ contributions, we can treat — or better still, prevent — this and so many other infectious diseases…and Texas Biomed is squarely focused on this.” — Suzy and Cappy Lawton and family
“As members of the baby boomer generation, Jessie and I grew up thinking antibiotics would cure almost all infections. Sadly, the evolution of “bad bugs” makes that comfortable belief no longer true. It shocked us to learn that by 2050, infectious diseases will be the leading cause of death in the world. We are passionate about supporting Texas Biomed to help find cures for infections and make our children’s and grandchildren’s lives and the lives of billions of others safer and healthier.” — Richard and Jessie Kardys
“Infectious diseases are still the #1 killer globally and the risk for pandemics increases each year. Texas Biomed stands alone with its assets, talent and focus to make breakthroughs that will impact all of us. We can't think of a better cause to ensure we make progress on these diseases for all of humanity.” — Lew and Laura Moorman
7
NONPROFIT ORGANIZATION U.S. POSTAGE
PAID
P.O. Box 760549 San Antonio, TX 78245
SAN ANTONIO, TEXAS PERMIT No. 958
A Note from the President/CEO We are making progress
B
iomedical research is defined as science that looks for ways to prevent and treat diseases that cause illness and death in people and in animals. When there is a breakthrough in our field, we celebrate. Our cover story in this issue of Progress is an example of victory over a disease that causes suffering and death. Texas Biomed researchers (and animals) have been critical to the successful development of a cure for hepatitis C — the first cure for a chronic viral disease. We are grateful to Mr. Lyons for sharing his personal story and struggle with a disease he no longer has to fight thanks to science. He has become part of a special group of advocates who are sharing their stories and fighting for science. For more than 75 years, Texas Biomed has been a reliable partner with organizations like the National Institutes of Health, Department of Defense, Bill & Melinda Gates Foundation, pharmaceutical companies and scientists worldwide to develop new ways to fight global health threats that are causing worldwide suffering.
the expertise of 75+ PhD scientists to speed up the development of new diagnostics, therapies and vaccines for some of the world’s deadliest diseases. And we continue to grow, adding scientific expertise and expanding our grant portfolio as described in this issue’s scientific briefs. We are making Progress.
Larry S. Schlesinger, M.D.
Our goal is to save millions of lives locally and globally from the threat of infection, and to do that requires community support, engagement and vision. We couldn’t be more grateful to our community and those who support our mission to eradicate the threat of infectious diseases. Thank you.
In an effort to save lives as fast as possible, Texas Biomed has combined its regulated, ethically-run resources with
Copyright ©2019 • www.txbiomed.org