Therapeutic approaches for codon reiteration diseases (360G-Wellcome-064354_Z_01_B)

£1,645,643

I aim to develop therapeutic strategies for diseases associated with protein misfolding and intracellular aggregation, focussing on Huntington's disease (HD) and oculopharyngeal muscular dystrophy (OPMD). First, I will develop our findings that levels of mutant huntingtin fragments can be reduced by inducing autophagy. This strategy attenuates toxicity of the HD mutation in transgenic cell, fly and mouse models. Recent work in cell and fly models suggests that autophagy induction is beneficial for a much broader range of targets, including polyglutamine expansions underlying many spinocerebellar ataxias, and tau. Currently, the only autophagy-inducing drug that is known to reduce mutant huntingtin levels effectively in mammalian brains is rapamycin. While it is designed for long-term use, it has significant side-effects. My aims in the context of this component of the proposal are:1. Further the understanding of the machinery and regulation of mammalian autophagy to aid discovery of safer and more specific targets.2. Test autophagy upregulation as a therapeutic strategy for SCA3 and tauopathies in mouse models. Second, I will exploit our OPMD mouse model for testing 4 known safe drugs/compounds in vivo, on the basis of pilot data showing that they reduce aggregation and toxicity in OPMD cell models.

Where is this data from?

This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.

Grant Details

Amount Awarded 1645643
Applicant Surname Rubinsztein
Approval Committee Clinical Interview Committee
Award Date 2006-06-05T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Senior Research Fellowship Clinical Renewal
Internal ID 064354/Z/01/B
Lead Applicant Prof David Rubinsztein
Partnership Value 1645643
Planned Dates: End Date 2012-08-31T00:00:00+00:00
Planned Dates: Start Date 2007-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof J. Paul Luzio