Muscle Man

This Houston biotech company hopes to one day fix your aging muscles

Houston-based Ridgeline Therapeutics isn't going to allow you beat aging, but someday it may well help you to live without muscle loss or diabetes. Getty Images

Stan Watowich's conversation flits with ease from restaurants to solving the homeless crisis. His active mind has made him a serial inventor. But the founder and current CEO of Ridgeline Therapeutics, a spin-off company of the University of Texas Medical Branch in Galveston where he is an associate professor of biochemistry and molecular biology, also has a razor-sharp focus when it comes to discussing his research. He wants to make it clear that he is not going to cure aging.

"You and I are still going to get old," he says. "But we have our hopes that as we get old our muscles will stay healthy."

He's talking about the drug candidate, RLT-72484. It has been shown to reactivate muscle stem cells and regenerate skeletal muscle in aged laboratory mice. We've all seen it in elderly humans: Your grandparents are shrunken from their younger selves because their muscles no longer regenerate at the rate that they once did.

"When you go to the gym, you feel that burn which indicates that you have muscle damage. Your stem cells are responsible for repairing this damage and building your muscles," Watowich explains. Stem cells simply don't repair at the same rate in older individuals.

That's why, for example, elderly people who break a hip often fare poorly in the aftermath. It's not uncommon to face a difficult period of physical therapy following hip fracture surgery. Many patients do not return to independent living. And, the mortality rate one year after a hip fracture can be as high as 30 percent. If RLT-72484 proves to work as well in humans as it does in animal models, it could make it easier for patients to gain muscle after a fall.

But even for healthy older adults, muscle decline can cause problems. Travel is difficult if you don't have the muscle strength for long walks. Playing with grandchildren is a challenge if your mobility is compromised. Watowich's vision is to prevent muscle decline or at least slow it down.

The drug could also potentially help muscular dystrophy patients. The genetic diseases identified under that umbrella diagnosis all cause muscle loss before old age, sometimes even in infancy. If RLT-72484 fulfills its promise, it could allow MD patients to live more normal lives.

In the University of Texas Medical Branch study, the mice's muscle fiber doubled in size while muscle strength increased by 70 percent. The team published a study last month describing its results. The next year will be spent on studies necessary to win FDA approval to begin testing on humans.

Muscle loss isn't the only big problem Ridgeline Therapeutics is seeking to address. Obesity-linked diabetes is also in Watowich's sights. His team has come up with a small molecule that shrinks fat tissue in obese animals. In studies published last year, mice lost seven percent of their body weight in 10 days of treatment without changing their diets. The animals remained obese, but their fat deposits had decreased in size by 30 percent. The drug on its own cannot make obese people thin, but it may help diabetics to return to a non-diabetic state.

Ridgeline Therapeutics is based in the Texas Medical Center. Watowich explains that 98 percent of biotech companies fail, so it's his goal to "stay lean" and use the $4.2 million award the company received from the Department of Defense to get their technologies into human trials. The company will likely move to the Johnson & Johnson Innovation Labs collaboration space in the next few months.

But of course, what Ridgeline Technologies has to offer is most exciting of all. Remember, it's not going to allow you beat aging. But someday it may well help you to live without muscle loss or diabetes.

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Building Houston

 
 

From biomolecular research to oral cancer immunotherapy, here are three research projects to watch out for in Houston. Photo via Getty Images

Research, perhaps now more than ever, is crucial to expanding and growing innovation in Houston — and it's happening across the city right under our noses.

In InnovationMap's latest roundup of research news, a couple local scientists are honored by awards while another duo of specialists tackle a new project.

University of Houston professor recognized with award

Mehmet Orman of UH has been selected to receive an award for his research on persister cells. Photo via UH.edu

Mehmet Orman, assistant professor of chemical and biomolecular engineering at the University of Houston Cullen College of Engineering has been honored with a Faculty Early Career Development Award from the National Science Foundation. The award comes with a $500,000 grant to study persister cells — cells that go dormant and then become tolerant to extraordinary levels of antibiotics.

"Nearly all bacterial cultures contain a small population of persister cells," says Orman in a news release. "Persisters are thought to be responsible for recurring chronic infections such as those of the urinary tract and for creating drug-resistant mutants."

Previously, Orman developed the first methods to directly measure the metabolism of persister cells. He also developed cell sorting strategies to segregate persisters from highly heterogeneous bacterial cell populations, and, according to the release, he will be using his methods in the NSF research project.

Houston researchers collaborate on oral cancer innovation

Dr. Simon Young of UTHealth and Jeffrey Hartgerink of Rice University are working on a new use for an innovative gel they developed. Photo via Rice.edu

Two Houston researchers — chemist and bioengineer Jeffrey Hartgerink at Rice University and Dr. Simon Young at the University of Texas Health Science Center at Houston — have again teamed up to advance their previous development of a sophisticated hydrogel called STINGel. This time, they are using it to destroy oral cancer tumors.

SynerGel combines a pair of antitumor agents into a gel that can be injected directly into tumors. Once there, the gel controls the release of its cargo to not only trigger cells' immune response but also to remove other suppressive immune cells from the tumor's microenvironment. The duo reported on the technology in the American Chemical Society journal ACS Biomaterials Science & Engineering.

SynerGel, combines a pair of antitumor agents into a gel that can be injected directly into tumors, where they not only control the release of the drugs but also remove suppressive immune cells from the tumor's microenvironment.

"We are really excited about this new material," Hartgerink says in a news release. "SynerGel is formulated from a specially synthesized peptide which itself acts as an enzyme inhibitor, but it also assembles into a nanofibrous gel that can entrap and release other drugs in a controlled fashion.

In 2018, the pair published research on the use of a multidomain peptide gel — the original STINGel — to deliver ADU-S100, an immunotherapy drug from a class of "stimulator of interferon gene (STING) agonists."

The research is supported by the Oral and Maxillofacial Surgery Foundation, the National Institutes of Health, the Welch Foundation, the National Science Foundation and the Mexican National Council for Science and Technology.

Texas Heart Institute researcher honored by national organization

Dr. James Martin of Texas Heart Institute has been named a senior member of the National Academy of Inventors. Photo courtesy of THI

The National Academy of Inventors have named Houston-based Texas Heart Institute's Dr. James Martin, director of the Cardiomyocyte Renewal Lab, a senior member.

Martin is an internationally recognized developmental and regenerative biologist and his research is focused on understanding how signaling pathways are related to development and tissue regeneration.

"Dr. Martin has long been a steward of scientific advancement and has proven to be a tremendous asset to the Texas Heart Institute and to its Cardiomyocyte Renewal Lab through his efforts to translate fundamental biological discoveries in cardiac development and disease into novel treatment strategies for cardiac regeneration," says Dr. Darren Woodside, vice president for research at THI, in a news release. "Everyone at the Texas Heart Institute is thrilled for Dr. Martin, whose induction into the NAI as a Senior Member is well-deserved."

Martin has authored over 170 peer-reviewed papers in top journals he holds nine U.S. patents and applications, including one provisional application, all of which have been licensed to Yap Therapeutics, a company he co-founded.

The full list of incoming NAI Senior Members, which includes three professionals from the University of Houston, is available on the NAI website.

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