This grant builds upon the research from a prior grant: Assessing the Neuroprotective Factor REST/NRSF as a Therapeutic Target for Parkinson’s Disease
Study Rationale: Studies have shown that a regulatory factor called REST could promote the survival of neurons in neurodegenerative conditions. This factor is produced in greater quantities with age, and is lost in pathological conditions, leaving neurons in the brain vulnerable to various forms of pathological stress. Several independent laboratories have linked these observations to Parkinson’s disease (PD). In this study, we therefore aim to determine whether REST will prove an attractive target for therapeutic intervention in PD.
Hypothesis: We hypothesize that reintroducing REST in the brains of preclinical PD models will alleviate parkinsonian traits in these animals, providing evidence that REST may be a viable target for PD therapeutics.
Study Design: We propose to use two different state-of-the-art preclinical PD mouse models that display several parkinsonian traits, including movement impairments, neuronal loss and the pathologic accumulation of alpha-synuclein. Using advanced gait analysis, we will carefully study the movement impairments of the animals before and after reintroducing REST. We will count the number of neurons before and after REST treatment and thereby evaluate whether REST administration provides a neuroprotective function. Finally, we will analyze whether REST therapy reduces the pathological accumulation of alpha-synuclein, further protecting the remaining neurons.
Impact on Diagnosis/Treatment of Parkinson’s disease: This study will determine whether REST is an appropriate target for PD. Because drug discovery is a very complicated and expensive process, establishing whether REST is a good target for PD is crucial before we invest time and effort searching for compounds that restore its function.
Next Steps for Development: Should this study prove that REST is a viable target for PD, we would search for drugs that can activate this protein in the brain. A REST activator could slow or stop neurodegeneration, providing significant benefits for people with PD.