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Parkinson’s disease drug hunters think outside the α-synuclein box

Nature Biotechnology volume 40, pages 1705–1707 (2022)Cite this article

Recent trial failures have called into question the central role of α-synuclein in Parkinson’s disease pathology. Although many continue to target α-synuclein aggregates in the brain, others are paying attention to the endolysosomal pathway, mitochondria and even glucose metabolism.

Some drug hunters have pivoted and are now pursuing other factors — dysfunctional mitochondria, proteasome dysregulation, impaired autophagy, defective lysosomes and neuroinflammation — involved in neurodegeneration. In November, London-based NRG Therapeutics announced a $16 million series A to apply the company’s first-in-class investigational small molecules, aimed at protecting mitochondria, in PD and other neurodegenerative disorders. In September, Pretzel Therapeutics announced $72.5 million in series A funding for their preclinical pipeline of small molecules and gene therapy aimed at mitochondrial DNA in PD and other neurodegenerative diseases. “There is never any good time to get the diagnosis of Parkinson’s,” says J. Timothy Greenamyre, director of the Pittsburgh Institute for Neurodegenerative Diseases, “but this is probably the best time in history, given what’s on the horizon.”

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    Ben Johnson

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Johnson, B. Parkinson’s disease drug hunters think outside the α-synuclein box. Nat Biotechnol 40, 1705–1707 (2022). https://doi.org/10.1038/s41587-022-01610-w

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