Cambridge, Mass. — Lysoway Therapeutics, a clinical-stage biotechnology company developing therapies targeting lysosomal ion channels, announced the publication of preclinical data evaluating its lead candidate, LW-1017, in Scientific Reports.
The study evaluated LW-1017, a small-molecule agonist of transient receptor potential mucolipin-1, or TRPML1, in preclinical models of Parkinson’s and Alzheimer’s diseases.
According to the company, LW-1017 demonstrated potent and selective activation of TRPML1, with effects on pathways involved in autophagy and lysosomal function. Oral dosing also produced brain exposure and sustained modulation of autophagy-lysosomal biomarkers in vivo.
In aged Parkinson’s disease models, LW-1017 reduced pathological alpha-synuclein, preserved dopaminergic neurons and improved motor function. In aged Alzheimer’s disease models, the treatment reduced amyloid and tau pathology, decreased neuroinflammation and improved cognition.
“This study provides the first in vivo evidence that pharmacological activation of TRPML1 restores autophagy–lysosomal function and produces coordinated molecular, cellular, and functional benefits in aged models of both Parkinson’s and Alzheimer’s diseases,” said Yongchang Qiu, Ph.D., Founder and Chief Executive Officer of Lysoway Therapeutics.
Qiu said LW-1017 achieved sustained central target engagement at oral doses as low as 3 mg/kg. He added that a less brain-penetrant but similarly potent comparator did not produce the same level of benefit in a head-to-head test at 30 mg/kg.
LW-1017 is currently being evaluated in a Phase 1 single ascending dose and multiple ascending dose clinical trial in healthy volunteers to assess its safety, tolerability and pharmacokinetics.
The research was supported in part by grants from the Michael J. Fox Foundation for Parkinson’s Research and The Silverstein Foundation for Parkinson’s with GBA.
