New Era in disease modification in Parkinson's disease: Review of genetically targeted therapeutics

Parkinsonism Relat Disord. 2019 Feb;59:32-38. doi: 10.1016/j.parkreldis.2018.10.025. Epub 2018 Oct 23.


Disease modification remains a major unmet need in Parkinson's disease (PD) therapeutics. Despite multiple attempts, not a single study has yet been successful, perhaps due to our incomplete understanding of the underlying disease mechanisms. Genetic and epidemiologic studies of the last decade have substantially increased our comprehension of the etiology of PD. Once considered a pure sporadic disease, the discovery of familial mutations provided the initial paradigm shift and it is now widely accepted that PD has a substantial genetic component. These genetic discoveries have allowed the development of novel therapeutics aimed at halting or slowing the underlying disease process, rather than just ameliorating symptoms. Here, we discuss the latest advances in therapeutics based on three genetic discoveries (SNCA, LRRK2 and GBA) that are currently reaching the clinical arena and outline the challenges of therapeutic development of genetically targeted therapeutics.

Keywords: Clinical trials; Disease modification; Genetics; Parkinson's disease.

Publication types

  • Review

MeSH terms

  • Biological Therapy*
  • Glucosylceramidase* / drug effects
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2* / drug effects
  • Parkinson Disease / therapy*
  • alpha-Synuclein* / drug effects


  • SNCA protein, human
  • alpha-Synuclein
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • GBA protein, human
  • Glucosylceramidase