Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Feb 14;21(3):10.
doi: 10.1007/s11910-021-01093-3.

Huntington's Disease: New Frontiers in Therapeutics

Ling Pan  1 , Andrew Feigin  2
Affiliations
Review

Huntington's Disease: New Frontiers in Therapeutics

Ling Pan et al. Curr Neurol Neurosci Rep. .

Abstract

Purpose of review: This article describes and discusses new potential disease-modifying therapies for Huntington's disease that are currently in human clinical trials as well as promising new therapies in preclinical development.

Recent findings: Multiple potential disease-modifying therapeutics for HD are in active development, including direct DNA/gene therapies, RNA modulation, and therapies targeted at aberrant downstream pathways. The etiology of Huntington's disease (HD) is well-known as an abnormally expanded trinucleotide repeat within the huntingtin gene. However, the pathogenesis downstream of the mutant huntingtin gene is complex, involving multiple toxic pathways, including abnormal protein fragmentation and neuroinflammation. The current treatment of HD focuses largely on symptomatic management. This article discusses new, potential disease-modifying therapies that are currently in human clinical trials and preclinical development.

Keywords: Clinical trials; Disease-modifying therapy; Gene therapy; Huntington’s disease; RNA interference.

PubMed Disclaimer

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
    1. Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N. The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis. Mov Disord. 2012;27(9):1083–91. https://doi.org/10.1002/mds.25075 . - DOI - PubMed
    1. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. The Huntington’s Disease Collaborative Research Group. Cell. 1993;72(6):971–83. https://doi.org/10.1016/0092-8674(93)90585-e .
    1. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell. 1996;87(3):493–506. https://doi.org/10.1016/s0092-8674(00)81369-0 . - DOI - PubMed
    1. Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell. 1997;90(3):537–48. https://doi.org/10.1016/s0092-8674(00)80513-9 . - DOI - PubMed
    1. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science. 1997;277(5334):1990–3. https://doi.org/10.1126/science.277.5334.1990 . - DOI - PubMed

Substances