A new study led by Maria Xilouri published in Science Advances demonstrates that a novel gene therapy targeting the LAMP2A gene successfully protects brain cells and improves motor and cognitive functions in a non-human primate model of Parkinson’s disease.

Parkinson's disease is characterized by the toxic accumulation of a protein called alpha-synuclein (αSyn) which forms destructive clumps known as Lewy bodies (LBs), leading to the death of vital dopamine-producing neurons. Cells rely on a specialized recycling process called Chaperone-Mediated Autophagy (CMA) to clear out these dangerous proteins. CMA declines naturally with ageing and has also been reported to be impaired in patients with Parkinson’s disease. The rate-limiting receptor for this system is LAMP2A (Lysosome-Associated Membrane Protein 2, isoform A).

By delivering a functional LAMP2A gene directly to the affected brain regions using an engineered adeno-associated virus vector (AAV9), researchers were able to reactivate this internal cleanup mechanism and protect nigral dopaminergic neurons from LB-induced αSyn neurodegeneration, delayed the formation and release of pathology-related αSyn species, and evoked a beneficial effect on motor behavior and on cognitive functions of the primate model. Such findings provide preliminary preclinical evidence supporting CMA enhancement as a therapeutic strategy for Parkinson’s disease and related αSynucleinopathies.

LAMP2A gene therapy mitigates Parkinson's disease-related pathology in nonhuman primates
Arotcarena ML, Fouka M, Gialinaki EG, Giannopoulou M, Jadot H, Darricau M, Lovisotto A, Dovero S, Planche V, Balpe E, Achour M, Thiolat ML, Dutheil N, Li Q, Noe E, Pioli EY, Harhouri K, Steinschneider R, Kirik D, Jensen NM, Jensen PH, Stefanis L, Bezard E, Dehay B, Xilouri M. Sci Adv. 2026 Oct 30;12(44):eaeg1787. doi: 10.1126/sciadv.aeg1787. Epub 2026 Oct 30. PMID: 42962009

pubmed
Science Advances
 

Press release/comments of the paper

https://en.mondosanita.it/news/studies-and-research/113719/parkinson-a-gene-therapy-aims-to-reactivate-protein-recycling.html

https://www.alzforum.org/papers/lamp2a-gene-therapy-mitigates-parkinsons-disease-related-pathology-nonhuman-primates

https://jclub.com.au/a/42962009

https://x.com/ScienceofPD/status/2116526493425713596