Montara Therapeutics announced that it has received a research grant of approximately $1 million from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) to advance a new Parkinson’s disease program based on its BrainOnly platform technology.
The non-dilutive funding marks the company’s second grant from MJFF, following a 2025 award supporting the development of a brain-selective LRRK2 inhibitor. The new project will focus on developing therapies that target the mTOR pathway, with the goal of activating the brain’s natural protein-clearing processes to reduce toxic α-synuclein accumulation, a hallmark of Parkinson’s disease.
The research is being supported through MJFF’s Therapeutics Pipeline Program, which funds preclinical and clinical initiatives aimed at accelerating the development of new Parkinson’s treatments.
Parkinson’s disease is characterized in part by the buildup of α-synuclein protein aggregates that damage neurons over time. One promising therapeutic strategy involves activating autophagy, a natural cellular process that clears damaged proteins and cellular components. The mTOR pathway regulates this process by suppressing autophagy when active. Inhibiting mTOR can activate cellular protein-clearing mechanisms and has shown promise in preclinical Parkinson’s models.
However, mTOR inhibitors such as rapamycin and related compounds have historically faced significant safety challenges because mTOR plays critical roles throughout the body. Systemic inhibition can lead to immune suppression, impaired wound healing, and metabolic complications, limiting the therapeutic use of these drugs in neurological diseases.
Montara aims to address this challenge through its BrainOnly platform, which combines a brain-penetrant therapeutic with a proprietary peripheral blocker designed to prevent activity outside the central nervous system. The approach seeks to enable brain-specific pharmacology while minimizing harmful systemic side effects.
The Parkinson’s program builds on Montara’s existing work in tuberous sclerosis complex (TSC)-related epilepsy, where the company is advancing MT1110, a proprietary peripheral blocker used in combination with the mTOR inhibitor everolimus.
Under the collaboration with MJFF, Montara will evaluate several clinically utilized mTOR inhibitors paired with its peripheral blocker technology to identify two-drug combinations capable of selectively activating autophagy in the brain. Candidate therapies will be tested in cellular systems and animal models of Parkinson’s disease to assess their ability to reduce α-synuclein accumulation, improve disease pathology, and maintain favorable safety profiles.
If successful, the program could establish a new therapeutic strategy aimed at slowing or potentially halting Parkinson’s disease progression by enhancing the brain’s ability to clear toxic protein buildup.
Montara Therapeutics is a preclinical-stage biotechnology company focused on developing brain-selective therapies for neurological diseases. The company’s BrainOnly platform is designed to enable safer and more effective treatments by restricting therapeutic activity to the brain while reducing unwanted effects in the rest of the body.
KEY QUOTES:
“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. MJFF’s continued support reflects the importance of exploring new approaches to Parkinson’s disease biology. The mTOR 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.”
Nicholas T. Hertz, Ph.D., Founder And CEO, Montara Therapeutics
“The mTOR pathway represents an important area of investigation in Parkinson’s research. 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.”
Jessica Tome Garcia, Lead Scientific Program Manager, Translational Research, The Michael J. Fox Foundation For Parkinson’s Research
“Our own genome-wide screens in human neurons identified mTOR 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.”
Martin Kampmann, Professor Of Biochemistry And Biophysics, UCSF, And Scientific Co-Founder, Montara Therapeutics
