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PARKINSON DISEASE

First trials test targeting of α-synuclein for Parkinson disease

In the first two phase II trials of therapies that target α-synuclein to treat Parkinson disease, the primary endpoints were not met. However, the limitations of these studies need to be addressed in future trials and alternative approaches to targeting α-synuclein should be pursued before α-synuclein is discounted as a target.

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References

  1. Devine, M. J. et al. Parkinson’s disease induced pluripotent stem cells with triplication of the α-synuclein locus. Nat. Commun. 2, 440 (2011).

    Article  PubMed  Google Scholar 

  2. Spillantini, M. G. et al. Alpha-synuclein in Lewy bodies. Nature 388, 839–840 (1997).

    Article  CAS  PubMed  Google Scholar 

  3. Laperle, A. H. et al. iPSC modeling of young-onset Parkinson’s disease reveals a molecular signature of disease and novel therapeutic candidates. Nat. Med. 26, 289–299 (2020).

    Article  CAS  PubMed  Google Scholar 

  4. Pagano, G. et al. Trial of prasinezumab in early-stage Parkinson’s disease. N. Engl. J. Med. 387, 421–432 (2022).

    Article  CAS  PubMed  Google Scholar 

  5. Lang, A. E. et al. Trial of cinpanemab in early Parkinson’s disease. N. Engl. J. Med. 387, 408–420 (2022).

    Article  CAS  PubMed  Google Scholar 

  6. Jankovic, J. et al. Safety and tolerability of multiple ascending doses of PRX002/RG7935, an anti-α-synuclein monoclonal antibody, in patients with Parkinson disease: a randomized clinical trial. JAMA Neurol. 75, 1206–1214 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Brys, M. et al. Randomized phase I clinical trial of anti-α-synuclein antibody BIIB054. Mov. Disord. 34, 1154–1163 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Shahnawaz, M. et al. Development of a biochemical diagnosis of Parkinson disease by detection of α-synuclein misfolded aggregates in cerebrospinal fluid. JAMA Neurol. 74, 163–172 (2017).

    Article  PubMed  Google Scholar 

  9. Meng, Y. et al. Putaminal recombinant glucocerebrosidase delivery with magnetic resonance-guided focused ultrasound in Parkinson’s disease: a phase I study. Mov. Disord. https://doi.org/10.1002/mds.29190 (2022).

    Article  PubMed  Google Scholar 

  10. Shin, S.-M. et al. Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects after systemic administration. Nat. Commun. 8, 15090 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

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Correspondence to Lorraine V. Kalia.

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L.V.K. has received consultation fees from AC Immune and UCB in the past year.

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Kalia, L.V. First trials test targeting of α-synuclein for Parkinson disease. Nat Rev Neurol 18, 703–704 (2022). https://doi.org/10.1038/s41582-022-00726-6

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