Preclinical development of an amelioration therapy for Dentatorubro-Pallidoluysian Atrophy - FUNDING EXTENSION
Ataxia UK
Inserm
Dentatorubro-Pallidoluysian Atrophy (DRPLA) is a polyglutamine ataxia caused by mutations in the ATROPHIN-1 gene, for which no cure is available. This group have significant experience in models of ataxia and spastic paraplegia with ataxia, and in particular of DRPLA. Following the recent success of antisense oligonucleotide (ASO) approaches in Huntington’s Disease - a polyglutamine syndrome with many genetic similarities to DRPLA - this group plan to apply their expertise to this preclinical study aimed at developing an ASO therapy for DRPLA. This group will test a batch of ASOs designed against the Atrophin-1 mRNA. The efficacy of the two best performing ASOs will be further studied in a well characterised mouse model (ATN1-65Q-FL). They plan to measure changes in the behavioural, histopathological and transcriptomic hallmarks of DRPLA. The group hope that at the end of this project, it may be possible to translate this therapy into a clinical trial for DRPLA patients.
2.1 Biological and endogenous factors