Study Rationale: Parkinson’s disease (PD) and other devastating neurodegenerative diseases, including Dementia with Lewy bodies (DLB) and Multiple System Atrophy (MSA), are characterized by the accumulation of abnormal clumps of alpha-synuclein protein inside nerve cells. As the disease progresses and symptoms worsen, the density and distribution of these aggregates progressively increases. For this reason, we believe that a drug that prevents the formation or spreading of alpha-synuclein aggregates within nerve cells will stop or delay the progression of PD. In this study, we aim to develop drugs that inhibit alpha-synuclein aggregation in the nervous system as a new therapy for PD.
Hypothesis: We hypothesize that inhibiting alpha-synuclein aggregation inside nerve cells will slow the worsening of symptoms of PD.
Study Design: Using AC Immune’s proprietary MorphomerTM small molecule library, we have identified compounds that potently inhibit alpha-synuclein aggregation when tested in cells in the laboratory. In this study, we will build on and improve the properties of these candidate molecules by introducing small, targeted changes in their chemical structures to enhance their effectiveness. Those that display the strongest inhibition of alpha-synuclein aggregation in cells will be evaluated in preclinical models of Parkinson’s disease to further assess their efficacy.
Impact on Treatment of Parkinson’s disease: Small molecules that inhibit alpha-synuclein aggregation have great potential for slowing the progression of PD, improving the quality of life for people with this disorder. We anticipate that such a medication can be taken in form of pills or capsules, making this treatment as convenient as it is efficacious.
Next Steps for Development: The successful completion of this study would allow a first, “lead”, molecule to advance into preclinical development toward an Investigational New Drug (IND) application and future testing in human clinical trials.