Montara Therapeutics Secures $1M Michael J. Fox Foundation Grant to Advance Brain-Selective mTOR Therapy for Parkinson's Disease
Key Insights
Montara Therapeutics (search) received approximately $1 million from The Michael J. Fox Foundation to develop a BrainOnly™ therapy targeting mTOR (search) for Parkinson's disease (search).
The program aims to activate autophagy in the brain to clear toxic α-synuclein (search) protein buildup while avoiding systemic side effects that have historically plagued mTOR (search) inhibitors.
Montara's BrainOnly™ platform pairs a brain-penetrant mTOR (search) inhibitor with a proprietary peripheral blocker to restrict drug activity exclusively to the central nervous system.
Montara Therapeutics (search), a preclinical-stage biopharmaceutical company focused on brain-selective therapies, has been awarded a research grant of approximately $1 million from The Michael J. Fox Foundation for Parkinson's Research (MJFF) to advance a novel therapeutic strategy targeting the mTOR (search) pathway in Parkinson's disease (search). Announced June 2, 2026, the funding marks Montara's second grant from MJFF, following a May 2025 award to develop a brain-selective LRRK2 (search) inhibitor.
The new program will leverage Montara's proprietary BrainOnly™ platform to activate autophagy — the brain's natural protein-clearing machinery — with the goal of clearing toxic α-synuclein (search) aggregates that characterize Parkinson's disease (search) pathology, while mitigating the systemic adverse effects that have historically prevented mTOR (search) inhibitors from reaching patients with neurological conditions.
The mTOR (search)-Autophagy Axis in Parkinson's Disease (search)
Parkinson's disease (search) is characterized in part by the progressive accumulation of α-synuclein (search), a toxic protein that clumps together and damages neurons over time. A promising strategy for removing this protein involves activating autophagy, a natural cellular housekeeping process in which cells break down and recycle damaged components.
The mTOR (search) protein serves as a critical brake on autophagy: when mTOR is active, autophagy is suppressed; when mTOR is inhibited, the brake is released and the cell's protein-clearing machinery is switched on. Drugs that inhibit mTOR — a class that includes rapamycin and related compounds — have shown encouraging results in clearing α-synuclein (search) in laboratory models of Parkinson's disease (search). However, because mTOR plays essential roles throughout the body, systemic mTOR inhibition causes serious side effects, including immune suppression, impaired wound healing, and metabolic disruption, severely limiting the clinical utility of these drugs as neurological therapies.
The BrainOnly™ Platform Approach
Montara's BrainOnly™ platform is designed to address this challenge by pairing a brain-penetrant therapeutic with a proprietary peripheral blocker that prevents the drug from acting outside the brain. This two-drug combination strategy enables brain-specific pharmacology, allowing therapies to target mechanisms underlying neurological disease while minimizing harmful systemic effects.
The company is already advancing its proprietary peripheral blocker, MT1110 (search), toward the clinic in combination with everolimus, an mTOR (search) inhibitor, to treat tuberous sclerosis complex (search) (TSC)-related epilepsy — another disease driven by mTOR pathway hyperactivation. The Parkinson's program builds directly on that foundation, applying the same BrainOnly™ approach to a new indication where mTOR-driven autophagy could clear the toxic protein accumulation at the heart of the disease.
Program Scope and Scientific Rationale
Through the MJFF collaboration, funded under the Foundation's Therapeutics Pipeline Program — which supports preclinical and clinical efforts to accelerate new therapies for Parkinson's disease (search) — Montara will evaluate several clinically utilized mTOR (search) inhibitors combined with its proprietary peripheral blocker. The goal is to identify novel two-drug combinations that selectively activate autophagy in the brain.
The program will assess these combinations in cell-based systems and Parkinson's disease (search) animal models to determine which candidates most effectively reduce α-synuclein (search) accumulation, treat pathology, and exhibit favorable safety profiles. If successful, the project could yield a therapeutic strategy that safely enhances autophagy in the brain, helping remove toxic protein buildup and potentially slowing or even stopping disease progression.
"Our team has spent years working toward a therapy that doesn't just treat the symptoms of Parkinson's but addresses the underlying biology causing neurons to die," said Nicholas T. Hertz, Ph.D., Founder and CEO of Montara Therapeutics (search). "MJFF's continued support reflects the importance of exploring new approaches to Parkinson's disease (search) biology. The mTOR (search) pathway is one of the most powerful levers we have for clearing toxic proteins from the brain, and our platform may finally make it safe enough to use."
Expert Perspectives
"The mTOR (search) pathway represents an important area of investigation in Parkinson's research," said Jessica Tome Garcia, Lead Scientific Program Manager, Translational Research at The Michael J. Fox Foundation. "While the underlying biology is compelling, challenges related to systemic toxicity have limited progress. This work aims to explore approaches that may help address those barriers and advance our understanding of how targeting mTOR-driven autophagy could impact disease biology."
Martin Kampmann, Ph.D., Professor of Biochemistry and Biophysics at UCSF and a Scientific Co-Founder of Montara Therapeutics (search), added: "Our own genome-wide screens in human neurons identified mTOR (search) signaling as one of the key pathways controlling the accumulation of toxic protein aggregates — and a target with real therapeutic potential. The challenge has always been that you cannot inhibit mTOR systemically without serious consequences for the rest of the body. Montara's BrainOnly™ platform is the most compelling approach I've seen for solving that problem, and this program gives us a direct path to test whether brain-selective mTOR inhibition can reduce pathological protein buildup in Parkinson's disease (search)."
Montara Therapeutics (search) is supported by an investor group that includes founding investor SV Health Investors' Dementia Discovery Fund, Two Bear Capital, KdT Ventures, Dolby Family Ventures, and BEVC.