Webinar
Small molecule activation of TRPML1 for the treatment of degenerative disorders
6 May 2025
16.00 CEST / 10.00 EDT / 07.00 PDT
About this webinar:
Key proteins involved in autophagy and lysosomal function are genetically- and immunohistochemically- linked to degenerative disorders.
Parkinson’s disease (PD) patients and amyotrophic lateral sclerosis (ALS) patients exhibit deficits in macroautophagy (MA) and lysosomal biogenesis (LB), supporting the development of therapeutic approaches, which can rectify deficits in MA and LB. TRPML1 activation triggers localized calcium release, which activates TFEB-mediated LB and MA.
Libra Therapeutics has an active, small molecule TRPML1 agonist program in IND-enabling safety and toxicology studies for the treatment of select neurodegenerative indications, including PD and ALS. In vitro, Libra TRPML1 agonists augment macroautophagy and lysosomal biogenesis to reduce pathologic proteins in iPS neuronal and recombinant cellular systems. In vivo, oral administration of Libra TRPML1 agonists activates macroautophagy and lysososomal biogenesis signaling in the brain cortex of wild type and transgenic mouse models of both synucleinopathy and SOD-opathy.
Libra’s first development candidate has advanced through in vitro safety profiling and in vivo non-clinical exploratory and dose range finding studies.
Libra’s first development candidate currently is in IND-enabling safety pharmacology and in vivo toxicology studies to support advancement into the Phase 1 safety clinical trials in 2026.
Keywords:
TRPML1, activation, macroautophagy, lysosomal biogenesis, PD, ALS
Speakers:
Martin Gill – SVP & Head of Research, Libra Therapeutics
Maria Pia Catalani – Director Lead Discovery Services, Axxam
Marty Gill serves as Senior Vice President and Head of Research for Libra Therapeutics, where he manages external CROs to develop disease-modifying treatments for central nervous system (CNS) indications with high unmet medical need.
Prior to joining Libra, Marty served as Head of In Vitro Discovery at Neuropore Therapies, focusing on mechanisms that reduce inflammation and/or reduce protein pathology associated with CNS degenerative disease. Marty also served as a project leader at Bristol Myers Squibb for traditional small molecule portfolio programs, as well as novel therapeutic modalities, targeting pathogenic mechanisms associated genetically-defined disease. Marty received his B.A. from the University of Missouri-Columbia and his Ph.D. from the University of Texas Medical Branch.
Maria Pia Catalani is the Director of the Lead Discovery Department in Axxam. She joined Axxam in November 2019 as Head of the Discovery Chemistry Group, becoming then in 2022 Head of the Hit Tailoring Solution Group. Prior to Axxam Maria Pia Catalani has worked in Evotec (Verona, Italy) and Aptuit (Verona, Italy) within different therapeutic areas (CNS, GI, Inflammation etc) and managing as Chemistry Leader several programs (H2L, LO). Maria Pia Catalani started her carrier as Medicinal Chemist in the pharmaceutical industry in 2005 in the PsyCEDD, GlaxoSmithKline Medicines Research Centre based in Verona where she built her knowledge in the field of Medicinal Chemistry working on projects from hit to candidate selection in the CNS area. Maria Pia has obtained her master’s degree in Medicinal Chemistry at the University of Pisa (Italy) and progressed her studies with her PhD in Chemical Sciences at the University of Florence. She is co-author and co-invetor of several publications and patents.