Natural History Study in Prodromal and Manifest Huntington Disease(HD)
Research type
Research Study
Full title
Natural History Study in Prodromal and Manifest Huntington Disease (HD) Gene Expansion Carriers (HDGECs) - SHIELD HD
IRAS ID
278819
Contact name
Anne Rosser
Contact email
Sponsor organisation
Triplet Therapeutics
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Huntington Disease (HD) is a chronic progressive condition that causes relentless loss of cognitive, emotional, and motor function. Options are available for treating symptoms, but no medical care that can stop or reverse HD exists.
HD is caused by a mutation in DNA (deoxyribonucleic acid). In the case of HD, the mutant (faulty) gene is called Huntingtin (HTT).
In this study researchers want to look at the faulty HTT gene and genes that can influence the faulty HTT gene. The faulty HTT gene is shown to be unstable and continues to expand and become longer as individuals with HD age. This is called somatic expansion. The more expanded and longer the faulty HTT gene becomes, the more it is unstable and prone to further expansion, which leads to increasing toxicity in the brain.
Researchers have shown the instability of the faulty HTT gene is influenced by DNA damage repair (DDR) genes. These genes are important for surveilling and repairing DNA during an individuals’ lifetime. But encountering the elongated faulty HTT gene, proteins encoded by the DDR genes can maladapt, inducing further expansion of the faulty HTT gene and thus increase its toxic effects. This mechanism has been studied in mice and humans carrying the faulty HTT gene. The human data corroborated and expanded preclinical findings illustrating DDR gene variants have significant impact on age of onset and disease progression in HD. Targeting a DDR gene has the potential to prevent or treat HD, and other similar diseases, at its root, namely to stop or slow the continued expansion of the faulty, elongated gene.
The data from this natural history study will be used to guide the design of a future interventional treatment trial in HD that aims at delaying onset and slowing progression of HD by targeting a DDR gene.REC name
Wales REC 5
REC reference
20/WA/0177
Date of REC Opinion
24 Jun 2020
REC opinion
Favourable Opinion