Happy to share that a project with the participation of BioSIM was selected for funding through the CaixaResearch Health Call 2024. This project was one of the 29 research projects selected for funding (out of the 580 applications, success rate of 5.0%) and is among the 9 Portuguese projects chosen.
This project, entitled “New molecules harnessing targeted protein degradation for the treatment of Machado-Joseph disease” will be headed by Patrícia Maciel (ICVS, Univ Minho), and will be developed with the collaboration with Fernanda Borges (CIQUP, Univ Porto) and Sérgio F. Sousa (BioSIM, LAQV-FMUP, Univ Porto), and will receive 1 million euros of funding.
Machado-Joseph disease is a rare inherited neurodegenerative disorder that affects one or two cases per 100,000 population and primarily causes symptoms such as poor coordination of movements, unsteady gait (ataxia), weakness in arms and legs and difficulty with speech and swallowing. It is caused by mutation of a protein called ataxin-3, which tends to aggregate, leading to toxic effects on neurons and resulting in their progressive dysfunction and disappearance. In addition to gene therapies aimed at silencing the expression of the mutant gene, which are currently being tested and face several major challenges related to safety and effective delivery of the therapy to the affected regions of the brain, other therapies are being explored based on the administration of small molecules capable of inducing protein degradation.
This project will focus on the development of small bifunctional molecules that bind to both the mutated protein and the cellular machine responsible for protein degradation and elimination, based on computational modelling, artificial intelligence techniques, biomolecular simulations, organic syntheses and medicinal chemistry tools, to guide the selection and optimization of new molecules, for experimental testing. The goal is to develop these small molecules as a promising alternative to gene therapy to selectively eliminate the mutated proteins that cause this disorder in nerve cells.
