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Peer-reviewedCC BY-NCScience Advances

LAMP2A gene therapy mitigates Parkinson’s disease–related pathology in nonhuman primates

  • Marie-Laure Arotcarena1
  • Maria Fouka2
  • Elena G. Gialinaki2
  • Marianna Giannopoulou2
  • Hugo Jadot1
  • Morgane Darricau1
  • Anna Lovisotto1
  • Sandra Dovero1
  • Vincent Planche1
  • Elio Balpe1
  • Melyna Achour1
  • Marie-Laure Thiolat1
13 more authors
  • Nathalie Dutheil1
  • Qin Li3
  • Emilie Noe3
  • Elsa Y. Pioli3
  • Karim Harhouri4
  • Rémy Steinschneider4
  • Deniz Kirik5
  • Nanna M. Jensen6
  • Poul H. Jensen6
  • Leonidas Stefanis2,7
  • Erwan Bezard1
  • Benjamin Dehay1
  • Maria Xilouri2
7 affiliations
  1. 1Univ. de Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.
  2. 2Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 4, Soranou Efesiou Street, Athens 11527, Greece.
  3. 3Motac Neuroscience, F-33000 Bordeaux, France.
  4. 4Neuron Experts SAS, F-13015 Marseille, France.
  5. 5Brain Repair and Imaging in Neural Systems (B.R.A.I.N.S) Unit, Department of Experimental Medical Science, Lund University, BMC D11, 22184 Lund, Sweden.
  6. 6DANDRITE–Danish Research Institute of Translational Neuroscience and Department of Biomedicine, University of Aarhus, Aarhus C, Denmark.
  7. 7Professor of Neurology, First Dept of Neurology, National and Kapodistrian University of Athens Medical School, Athens, Greece.
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Abstract

Chaperone-mediated autophagy (CMA), regulated by its lysosomal receptor LAMP2A, is a key pathway for αSynuclein (αSyn) clearance and a direct target of αSyn-related neurotoxicity. Rodent studies show that LAMP2A enhancement reverses neurodegeneration, whereas its deficiency accelerates pathology. To test translational relevance, we examined whether increasing LAMP2A expression in nonhuman primates could mitigate α-synucleinopathy induced by injections of Parkinson's disease patient-derived Lewy body (LB) extract. Increasing LAMP2A expression protected 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. Our findings provide preliminary preclinical evidence supporting CMA enhancement as a therapeutic strategy for αSynucleinopathies.

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Cite

BibTeXRIS
BibTeX
@article{arotcarena2026lamp2a,
  title = {{LAMP2A gene therapy mitigates Parkinson’s disease–related pathology in nonhuman primates}},
  author = {Marie-Laure Arotcarena and Maria Fouka and Elena G. Gialinaki and Marianna Giannopoulou and Hugo Jadot and Morgane Darricau and Anna Lovisotto and Sandra Dovero and Vincent Planche and Elio Balpe and Melyna Achour and Marie-Laure Thiolat and Nathalie Dutheil and Qin Li and Emilie Noe and Elsa Y. Pioli and Karim Harhouri and Rémy Steinschneider and Deniz Kirik and Nanna M. Jensen and Poul H. Jensen and Leonidas Stefanis and Erwan Bezard and Benjamin Dehay and Maria Xilouri},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeg1787},
  url = {https://www.science.org/doi/abs/10.1126/sciadv.aeg1787},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - LAMP2A gene therapy mitigates Parkinson’s disease–related pathology in nonhuman primates
AU  - Marie-Laure Arotcarena
AU  - Maria Fouka
AU  - Elena G. Gialinaki
AU  - Marianna Giannopoulou
AU  - Hugo Jadot
AU  - Morgane Darricau
AU  - Anna Lovisotto
AU  - Sandra Dovero
AU  - Vincent Planche
AU  - Elio Balpe
AU  - Melyna Achour
AU  - Marie-Laure Thiolat
AU  - Nathalie Dutheil
AU  - Qin Li
AU  - Emilie Noe
AU  - Elsa Y. Pioli
AU  - Karim Harhouri
AU  - Rémy Steinschneider
AU  - Deniz Kirik
AU  - Nanna M. Jensen
AU  - Poul H. Jensen
AU  - Leonidas Stefanis
AU  - Erwan Bezard
AU  - Benjamin Dehay
AU  - Maria Xilouri
PY  - 2026
DA  - 2026/10/30
JO  - Science Advances
DO  - 10.1126/sciadv.aeg1787
UR  - https://www.science.org/doi/abs/10.1126/sciadv.aeg1787
AB  - Chaperone-mediated autophagy (CMA), regulated by its lysosomal receptor LAMP2A, is a key pathway for αSynuclein (αSyn) clearance and a direct target of αSyn-related neurotoxicity. Rodent studies show that LAMP2A enhancement reverses neurodegeneration, whereas its deficiency accelerates pathology. To test translational relevance, we examined whether increasing LAMP2A expression in nonhuman primates could mitigate α-synucleinopathy induced by injections of Parkinson's disease patient-derived Lewy body (LB) extract. Increasing LAMP2A expression protected 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. Our findings provide preliminary preclinical evidence supporting CMA enhancement as a therapeutic strategy for αSynucleinopathies.
SN  - 2375-2548
ER  -