MJFF funds promising therapy tackling Parkinson’s progression
$2.93M grant helps Lysoway advance a treatment targeting TRPML1 protein
Lysoway Therapeutics has received a $2.93-million grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF). The funding will advance a potential new therapy that targets the TRPML1 protein, a promising approach designed to modify the disease’s progression rather than just treating symptoms.
“This funding underscores growing confidence in TRPML1 as a compelling target for Parkinson’s disease,” Yongchang Qiu, Lysoway’s CEO, said in a company press release. “It will allow us to accelerate development of our lead TRPML1 agonist and to establish key biomarkers for target engagement, with the goal of initiating first-in-human clinical trials early next year.”
The grant is part of the foundation’s Parkinson’s Disease Therapeutics Pipeline Program, which supports preclinical and clinical research of therapies with the potential to ease symptoms or possibly prevent, stop, or delay disease progression. Currently, there are no approved disease-modifying therapies for Parkinson’s that target underlying disease processes.
Helping cells clear toxic clumps in brain
Lysoway’s approach focuses on helping cells clear toxic clumps of alpha-synuclein, a protein whose accumulation is believed to contribute to the neurodegeneration seen in Parkinson’s and other neurological disorders. As neurons die, the motor and nonmotor symptoms of Parkinson’s emerge and worsen over time.
In healthy cells, alpha-synuclein is typically broken down before it accumulates through a process called autophagy. Lysosomes are specialized structures within cells that are key to this process, recycling damaged proteins into their basic building blocks.
When autophagy is impaired, alpha-synuclein and other cellular stressors can build up. In some people with Parkinson’s, this breakdown in the clearance system may be linked to genetic mutations that affect proteins involved in lysosomal function.
To address defects in the cell’s waste-clearance system, Lysoway is developing a small molecule that can enter the brain and target TRPML1, a lysosomal ion channel located in the membranes of lysosomes. TRPML1 regulates calcium signaling that drives key steps in autophagy. Preclinical evidence suggests that activating TRPML1 can enhance the clearance of toxic alpha-synuclein aggregates and may ultimately slow or prevent disease progression.
“TRPML1 is a high value target due to its pivotal role in sensing and responding to cellular stress,” said Valerie Cullen, PhD, a senior vice president, and head of research and translational science at Lysoway. “By activating this ion channel, we can engage multiple beneficial pathways that restore autophagy/lysosomal homeostasis and bolster cellular resilience.”
These qualities offer “strong potential to modify disease progression in Parkinson’s Disease,” Cullen added.
Recently, the MJFF has identified the gene that codes for the TRPML1 protein as a priority therapeutic target in its Targets to Therapies Initiative.
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