Scenic joins LITE program to test Parkinson’s treatment approach
PLA2G15 inhibitors designed to improve lysosome function in preclinical models
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- Scenic Biotech is developing PLA2G15 inhibitors for Parkinson’s disease, including in people with LRRK2 gene mutations.
- Inhibiting PLA2G15 has been shown to increase BMP levels and improve measures of lysosomal disease in preclinical models.
- MJFF’s LITE program will test these inhibitors in preclinical models to support future clinical development.
Scenic Biotech has joined the LRRK2 Investigative Therapeutics Exchange (LITE) program to study its PLA2G15 inhibitors as a potential treatment approach for Parkinson’s disease, including in people with LRRK2 gene mutations.
The program is an initiative from The Michael J. Fox Foundation (MJFF) designed to identify biomarkers and accelerate the development of new disease-modifying therapies targeting LRRK2 biology. Mutations in LRRK2 are among the most common genetic causes of Parkinson’s.
The collaboration will focus on testing PLA2G15 inhibitors in validated preclinical models developed at the University of Dundee, in Scotland. The goal is to generate data that could support and accelerate future clinical development.
“With growing evidence that lysosomal dysfunction is believed to play a role in Parkinson’s, we will combine our first-in-class approach with LITE’s LRRK2 expertise, biomarker infrastructure, and leading academic models to test whether improving lysosomal function can deliver meaningful patient benefit,” Roland Bűrli, PhD, Scenic’s chief scientific officer, said in a company press release.
LITE program to test lysosome-focused approach
Shalini Padmanabhan, PhD, senior vice president of discovery and translational research at MJFF, added, “Scenic offers a unique perspective on LRRK2-related mechanisms, focusing on lysosomal health and lipid metabolism. We are pleased to welcome Scenic to the program and look forward to strengthening the evidence linking lysosomal biology to Parkinson’s disease.”
A hallmark of Parkinson’s is the formation of toxic clumps of misfolded alpha-synuclein protein in nerve cells, which are believed to contribute to their progressive dysfunction and death. Lysosomes are cellular compartments that help break down unwanted or damaged molecules. When lysosomes do not work properly, cells may have more difficulty clearing misfolded proteins such as alpha-synuclein.
PLA2G15, also known as lysosomal phospholipase A2, is a lysosomal enzyme that breaks down bis(monoacylglycero)phosphate, or BMP, a lipid that plays an important role in lysosome function. Inhibiting PLA2G15 has been shown to increase BMP levels and improve measures of lysosomal disease in preclinical models.
Studies have shown altered BMP profiles in Parkinson’s associated with certain GBA1 and LRRK2 mutations. GBA1 and LRRK2 mutations are among the most common genetic causes of Parkinson’s.
Scenic identified PLA2G15 through its Cell-Seq functional genomics platform and is developing brain-penetrant small-molecule inhibitors designed to raise naturally occurring BMP levels and restore lysosomal function.
“The PLA2G15-BMP axis offers a compelling way to explore how lysosomal biology intersects with LRRK2-linked Parkinson’s disease,” said Dario Alessi, PhD, director of the MRC Protein Phosphorylation Unit at the University of Dundee and LITE principal investigator. “By bringing Scenic’s inhibitors into the LITE framework, we can apply the models, tools, and biomarker expertise we have built at Dundee to better understand the translational potential of this approach.”
Scenic says its PLA2G15 program also has therapeutic potential in other neurological diseases associated with lysosomal dysfunction, including Batten disease, Niemann-Pick type C, and frontotemporal dementia.
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