Translating genetics of neurodegenerative disorders into therapeutic strategies.

Neurodegenerative disorders are extremely debilitating conditions. They affect motoric (ALS, Parkinson) or cognitive systems (Alzheimer, Frontotemporal dementia, Parkinson in late stages). Curative therapy is much needed but only symptomatic treatment based on neurotransmitter substitution is available for Parkinson, and more limited, for Alzheimer. All in all, for the advanced stages of neurodegenerative diseases, only palliative help can be offered. However, this grim perspective should change in the future. Research, especially in human genetics, has indeed yielded a dazzling amount of new insights. These, together with the progress in imaging and early diagnosis (especially in the Alzheimer field, other areas will follow) will lead to early risk determination and early diagnosis. In the near future people will be healthier, more functional and younger when diagnosed with these scourges. However, these promising new developments call for an intensification of the research effort towards real prospects for therapy. Translating the growing genetic information into mechanisms of disease and appropriate animal models is a vast scientific challenge for the next years. Furthermore, developing medication will require much deeper understanding of molecular and cellular mechanisms than we have today. Indeed, current drug development is frequently based on preliminary assumptions on the biology of the drug targets which have repetitively led to failures in clinical trials. In the new Methusalem grant we address these challenges.