Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

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

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lorraine V. Kalia.

Ethics declarations

Competing interests

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41582-022-00726-6

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing