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MEDICAL YEAR
IN REVIEW

Translating Discoveries into Healthier

Patients at UT Health

By Robert Hromas, MD

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.
UT 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, Dao- as the brain” Lechleiter said, and AST-004 is also effective at preventing
hong Zhou, MD and I have developed a degrader of the cancer sur- inner ear cell death after trauma from pressure blasts. AST-004 is in
vival protein BCL-XL. This drug, termed DT2216 is in phase 1 phase 1 trials in Europe, with phase 2 planned for the University Hos-
clinical trials at the UT Health San Antonio, Mays Cancer Center. pital Trauma Center.
Phase 2 trials will start after the first of the new year in T-cell lym- Fourth, Ratna Vadlamudi, PhD, Professor of Obstetrics and Gyne-
phoma, pediatric liver cancer and myelofibrosis, all diseases that are cology at the LSOM discovered a small molecule that was highly active
difficult to cure. Dr. Zhou was the first to use the proteolysis targeting against resistant breast cancers, ERX-41. He discovered that ERX-41
chimera (PROTAC) technology to overcome the on-target and dose- had robust activity against multiple Triple Negative Breast Cancer mo-
limiting toxicity of BCL-XL inhibitors. DT2216 targeted cancer cells lecular subtypes. Vadlamudi identified a novel therapeutic vulnerability
by converting a previously toxic BCL-XL inhibitor into a PROTAC in these and other resistant cancers that can be targeted to kill these
that targets BCL-XL to an E3 ligase minimally expressed in platelets hard-to-treat cancers in culture and animal models. His studies showed
but highly expressed in tumors. This makes DT2216 specific for many that when ERX-41 hit its target, the LIPA protein, it induces endo-
tumors, limiting its toxicity. plasmic reticulum stress in cancer cells, leading to cell death. He showed
Second, Associate professor of Neurosurgery, Ali Seifi, MD never that targeting LIPA and causing ER stress in cancer cells may be an ef-
thought he would be on Shark Tank, but his discovery, Hiccaway is so fective therapeutic strategy for resistant breast cancer and other difficult
effective at getting rid of hiccups, even in cancer patients who suffer to treat solid tumors.
from chronic debilitating hiccups, that he won a spot on the show. The LSOM research teams have made many other discoveries re-
Shark Mark Cuban liked his invention and invested in the company, cently that can ultimately impact many chronic diseases, such as dia-
which now markets Hiccaway in HEB and Amazon. Seifi thought the betes, steatorrhea hepatitis, dementia and muscle wasting in aging. We
first emails from ABC for Shark Tank were fake and ignored them. It are developing these interventions in San Antonio, which will markedly
was not until the main producer emailed him directly that he paid at- grow the biotechnology industry here, helping make San Antonio a
tention and accepted the invitation to be on the show. He had pub- hub for translating medical discoveries into patient care.
lished 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 Sys-
tems and Anatomy, found that a novel small molecule, AST-004 pro-
tected 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 Robert Hromas, MD, Dean of the Long School of Medicine at UT
after explosions. “The inner ear has a lot of the same neural structure Health San Antonio.

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