Casma Therapeutics Announces Publication in Science Advances Highlighting Novel Mechanism Related to TFEB Activation and Lysosomal Biology

Study demonstrates GABARAP-dependent TFEB activation plays a key role in regulating lysosomal homeostasis

CAMBRIDGE, Mass., Oct. 04, 2021 (GLOBE NEWSWIRE) — Casma Therapeutics, Inc., a biotechnology company harnessing the process of autophagy to design new medicines, today announced the publication of new research findings in Science Advances co-authored by Casma scientists, along with Oliver Florey, Ph.D., of the Brabraham Institute, and Casma scientific co-founder Andrea Ballabio, M.D., of the Telethon Institute of Genetics and Medicine. The study titled, “GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis” discusses a newly identified molecular mechanism that demonstrates the role of GABARAP-dependent regulation of transcription factor EB (TFEB) during the onset of autophagy.

TFEB is the master regulator of lysosomal function and is required for maintaining cellular and whole-body health. Lysosomes are organelles containing enzymes capable of breaking down and clearing toxic protein aggregates and storage material associated with human disease. TFEB regulates the levels of these enzymes, many of which are mutated in lysosomal storage disorders and neurodegeneration. While TFEB has been recognized as a promising therapeutic target, it is under the direct control of mechanistic target of rapamycin (mTOR), which is a central regulator of cellular homeostasis.

“TFEB has proven to be very beneficial in a variety of disease models and offers significant therapeutic potential. The Casma publication describes a novel mechanism to regulate TFEB activation without impacting the ability of mTOR to phosphorylate other targets involved in general cellular activity,” said Andrea Ballabio, M.D.

The Science Advances paper concluded that the GABARAP-FLCN/FNIP-TFEB axis serves as a molecular sensor that regulates lysosomal homeostasis within the autophagy-lysosomal network. This sensor mechanism was characterized using cellular and molecular biology principles as well as x-ray crystallography and biophysical techniques.

“We are excited that the findings from this study have evolved our understanding of how lysosomal capacity is regulated and why this is critical for maintaining cellular homeostasis,” said Leon Murphy, Ph.D., Chief Scientific Officer at Casma Therapeutics. “This study lays the foundation for continued research towards evaluating lysosomal dysfunction in disease and substantially broadens the potential for developing novel therapeutics in multiple disease areas.”

About Casma Therapeutics
Casma Therapeutics is harnessing autophagy by developing novel degradation approaches to open new target areas for drug discovery and development that will profoundly impact the lives of patients. Autophagy is a conserved cellular process that contributes to overall cellular homeostasis, but when autophagy is perturbed, inefficient autophagic flux contributes to numerous diseases. By selectively boosting autophagy and degradation of disease targets in the lysosome, Casma expects to be able to arrest or reverse the progression of disease processes such as neurodegeneration, metabolic disorders, inflammation, muscle degeneration and oncology. For more information, please visit www.casmatx.com.

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