Objective:
Our objective is to identify known, safe drugs that are useful for treating Parkinson’s disease (PD). Most drugs work by interacting with specific molecular ‘targets’ in the human body, such as enzymes, cell receptors, and DNA. Recently it has become clear that many drugs interact strongly with more than one target, and that most of these interactions are unknown. Such activities on unidentified targets can be the cause of side effects, but are also an opportunity for treating diseases mediated by these targets.
Project Description:
Systematic testing of all drugs against all human targets is prohibitively expensive. We have therefore developed a computational method to predict whether a drug is likely to be active against a given target. The method and experimentally confirmed predictions have been published in leading scientific journals [e.g. Keiser et al., Nature 462 (7270), 2009].
Intense activity by the PD research community has identified targets that may cause symptoms or disease progression, but no approved drugs are known to act at these targets. We will apply our method to predict whether known drugs interact with at least three of these, and test the predictions experimentally. Confirmed drugs will be evaluated for suitability as PD therapies based on their known safety and pharmacological profile. Although not part of this application, we intend to advance drugs that pass this process to human clinical trials and approval.
Relevance to Treatment of Parkinson’s Disease:
The drug-target combinations we are pursuing have the potential to arrest disease progression, treat disabling symptoms, or extend the useful life of therapies such as L-dopa. A drug already known to be safe could reach patients in one to four years, vs. seven to twelve years for a new molecule that has never been tested in humans.
Anticipated Outcome:
Over nine months, at a very low cost, we hope to have identified one or more known drugs active against an important PD target for advancement toward human trials. There is no guarantee that the drugs we evaluate will have activity against these targets, or that our method is sufficiently accurate to predict them. Based on past experience, however, we believe that the number of targets selected and our large database of known drugs provide a reasonable chance of success.