Huntington's Disease: Latest Frontiers in Therapeutics.
Curr Neurol Neurosci Rep
; 24(8): 255-264, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38861215
ABSTRACT
PURPOSE OF REVIEW Huntington's disease (HD) is an autosomal-dominant disorder caused by a pathological expansion of a trinucleotide repeat (CAG) on exon 1 of the huntingtin (HTT) gene. HD is characterized by the presence of chorea, alongside other hyperkinesia, parkinsonism and a combination of cognitive and behavioural features. Currently, there are no disease-modifying therapies (DMTs) for HD, and the only intervention(s) with approved indication target the treatment of chorea. This article reviews recent research on the clinical development of DMTs and newly developed tools that enhance clinical trial design towards a successful DMT in the future. RECENT FINDINGS:
HD is living in an era of target-specific drug development with emphasis on the mechanisms related to mutant Huntingtin (HTT) protein. Examples include antisense oligonucleotides (ASO), splicing modifiers and microRNA molecules that aim to reduce the levels of mutant HTT protein. After initial negative results with ASO molecules Tominersen and WVE-120101/ WVE-120102, the therapeutic landscape continues to expand, with various trials currently under development to document proof-of-concept and safety/tolerability. Immune-targeted therapies have also been evaluated in early-phase clinical trials, with promising preliminary findings. The possibility of quantifying mHTT in CSF, along with the development of an integrated biological staging system in HD are important innovations applicable to clinical trial design that enhance the drug development process. Although a future in HD with DMTs remains a hope for those living with HD, care partners and care providers, the therapeutic landscape is promising, with various drug development programs underway following a targeted approach supported by disease-specific biomarkers and staging frameworks.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Huntington
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Neurol Neurosci Rep
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Canadá