Research collaboration aims to clarify Parkinson’s disease pathways
Mair and Radboud University focus on TMEM175 function
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- Parkinson’s disease involves misfolded protein buildup that may be linked to impaired lysosome function and TMEM175.
- Altered forms of TMEM175 can disrupt lysosomal pH, limiting the breakdown of proteins such as alpha-synuclein.
- Researchers are developing TMEM175 agonists to support lysosomal function and improve clearance of misfolded proteins in Parkinson’s.
Mair Therapeutics is collaborating with Radboud University in the Netherlands to advance Parkinson’s disease research by developing small molecules designed to target TMEM175, a protein that genetic studies have linked to Parkinson’s risk.
“Parkinson’s disease remains one of the most pressing medical challenges of our time,” Vasily Kazey, PhD, Mair’s CEO, said in a company press release. “We are excited to collaborate with Radboud University, whose deep expertise in neuronal biology and Parkinson’s research will be instrumental in validating our therapeutic approach.”
Symptoms of Parkinson’s are partly linked to the buildup of damaged or misfolded proteins in nerve cells, particularly a protein called alpha-synuclein. Under normal conditions, nerve cells clear these proteins using structures called lysosomes, which act like recycling centers that break down unwanted material.
Understanding the role of TMEM175 in Parkinson’s
TMEM175 is an ion channel, a type of protein that helps move charged particles across cell membranes. It plays a role in maintaining a healthy internal environment inside lysosomes, in part by helping regulate pH, a measure of acidity. When this balance is disrupted, lysosomes may be less effective at breaking down unwanted material.
Genetic studies have shown that some mutated versions of TMEM175 do not function as well, which may impair lysosomes’ ability to clear unwanted material. In studies using mice that lacked TMEM175, researchers observed disrupted lysosomal pH regulation and increased accumulation of toxic alpha-synuclein, a protein linked to Parkinson’s disease.
Mair is developing small molecules designed to activate TMEM175. These compounds are intended to bind to the ion channel and support its normal activity, which could help maintain lysosomal pH balance and improve the breakdown of misfolded proteins.
In this collaboration, the laboratory of Marijn Kuijpers, PhD, an assistant professor at the Donders Centre for Neuroscience at Radboud University, will test Mair’s small molecules in models of human nerve cells, or neurons, derived from people diagnosed with Parkinson’s and from healthy donors. Researchers will measure lysosomal pH and the ability of lysosomes to degrade unwanted material.
The collaboration reflects Mair’s commitment to working closely with neuroscientists in the Netherlands. Mair, which was recently launched with support from Torrey Pines Investment and Oost NL, is based in Nijmegen, a city known for Parkinson’s research and home to a Parkinson’s expertise center led by Bas Bloem, MD, PhD, at Radboudumc.
