Unmet Need
An estimated 930K people in the US are living with a neurodegenerative disease (Alzheimer’s and Parkinson’s are most common). However, current standard of care treatments mostly addresses symptoms of these diseases. To date no disease modifying or neuroprotective treatments are approved for Parkinson, and only 1 recently has been for Alzheimer’s disease. A disease modifying or neuroprotective agent with blood brain barrier penetrating capability would have a significant impact on patient outcome. Therefore, there is a strong need for better therapies to be developed to address the growing burden of neurodegenerative diseases.
Technology Overview
Extracellular Vesicles (EVs) have increasingly been associated with the dissemination of harmful proteins in numerous neurological disorders. There is a growing focus on developing inhibitors for Neutral Sphingomyelinase 2 (nSMase2), a crucial enzyme involved in the formation of EVs. In light of this, researchers at Johns Hopkins Drug Discovery have identified orally available and brain-penetrable prodrugs of a previously identified nSMase2 inhibitor. These prodrugs hold potential utility in treating neurodegenerative diseases, including Alzheimer’s. The most promising prodrugs exhibit enhanced pharmacokinetics, pharmacodynamics, and brain penetration compared to the parent compound.
Stage of Development: Preliminary data shows improved pharmacokinetics and efficacy in animal models
Patent : US Issued Patent: 11,766,423
Publication
Pal A, Gori S, Yoo SW, Thomas AG, Wu Y, Friedman J, Tenora L, Bhasin H, Alt J, Haughey N, Slusher BS, Rais R. Discovery of Orally Bioavailable and Brain-Penetrable Prodrugs of the Potent nSMase2 Inhibitor DPTIP. J Med Chem. 2022 Aug 25;65(16):11111-11125. Epub 2022 Aug 5. PMID: 35930706;
