at UT Health By Robert Hromas, MD

Translating Discoveries into Healthier Patients at UT Health

By Robert Hromas, MD

UT

Health is a remarkable engine for biomedical discovery that is offering hope for previously incurable diseases. Translating these discoveries into clinical trials right here in San Antonio contributes greatly to the burgeoning biotechnology industry here. We highlight here three drugs and one device that will make lives better for patients with complex and difficult to treat diseases.

First, Director of the Center for Innovative Drug Discovery, Daohong Zhou, MD and I have developed a degrader of the cancer survival protein BCL-XL. This drug, termed DT2216 is in phase 1 clinical trials at the UT Health San Antonio, Mays Cancer Center. Phase 2 trials will start after the first of the new year in T-cell lymphoma, pediatric liver cancer and myelofibrosis, all diseases that are difficult to cure. Dr. Zhou was the first to use the proteolysis targeting chimera (PROTAC) technology to overcome the on-target and doselimiting toxicity of BCL-XL inhibitors. DT2216 targeted cancer cells by converting a previously toxic BCL-XL inhibitor into a PROTAC that targets BCL-XL to an E3 ligase minimally expressed in platelets but highly expressed in tumors. This makes DT2216 specific for many tumors, limiting its toxicity. Second, Associate professor of Neurosurgery, Ali Seifi, MD never thought he would be on Shark Tank, but his discovery, Hiccaway is so effective at getting rid of hiccups, even in cancer patients who suffer from chronic debilitating hiccups, that he won a spot on the show. Shark Mark Cuban liked his invention and invested in the company, which now markets Hiccaway in HEB and Amazon. Seifi thought the first emails from ABC for Shark Tank were fake and ignored them. It was not until the main producer emailed him directly that he paid attention and accepted the invitation to be on the show. He had published a study proving Hiccaway’s efficacy in JAMA, and he had strong patent protection, which made him an attractive participant for Shark Tank. The fact that hiccups is the third most common health search on Google combined to make an investment in Hiccaway much less risky for Cuban.

Third, Jim Lechleiter, PhD, Professor in the Department of Cell Systems and Anatomy, found that a novel small molecule, AST-004 protected astrocytes from death after stroke or brain trauma. The surviving astrocytes were able to protect other central nervous system tissue, and recovery from the brain events was quicker. AST-004 holds promise for multiple other indications besides stroke and concussions. His team discovered another possible use for the drug, preventing hearing loss after explosions. “The inner ear has a lot of the same neural structure as the brain” Lechleiter said, and AST-004 is also effective at preventing inner ear cell death after trauma from pressure blasts. AST-004 is in phase 1 trials in Europe, with phase 2 planned for the University Hospital Trauma Center.

Fourth, Ratna Vadlamudi, PhD, Professor of Obstetrics and Gynecology at the LSOM discovered a small molecule that was highly active against resistant breast cancers, ERX-41. He discovered that ERX-41 had robust activity against multiple Triple Negative Breast Cancer molecular subtypes. Vadlamudi identified a novel therapeutic vulnerability in these and other resistant cancers that can be targeted to kill these hard-to-treat cancers in culture and animal models. His studies showed that when ERX-41 hit its target, the LIPA protein, it induces endoplasmic reticulum stress in cancer cells, leading to cell death. He showed that targeting LIPA and causing ER stress in cancer cells may be an effective therapeutic strategy for resistant breast cancer and other difficult to treat solid tumors. The LSOM research teams have made many other discoveries recently that can ultimately impact many chronic diseases, such as diabetes, steatorrhea hepatitis, dementia and muscle wasting in aging. We are developing these interventions in San Antonio, which will markedly grow the biotechnology industry here, helping make San Antonio a hub for translating medical discoveries into patient care.

Robert Hromas, MD, Dean of the Long School of Medicine at UT Health San Antonio.