Novel Method Repurposes CsA-Type Compounds to Treat Neurodegenerative Disease
Alzheimer’s disease remains a challenging disorder for drug development, with many candidate drugs failing clinical trials. Our novel method repurposes camphorsulfonic acid (CsA)-type compounds to treat early-stage Alzheimer’s disease, as well as other neurodegenerative disorders, by inhibiting calcineurin, which affects signaling cascades linked to neurodegeneration and cognitive decline.
According to the CDC, in 2020 an estimated 5.8 million Americans 65 or older had Alzheimer’s disease, and the number is expected to reach 14 million by 2060. Drug development for Alzheimer’s disease has focused primarily on molecular targets that play a role in late neurodegenerative processes, rather than the early signaling pathways that cause the disease. One signaling protein thought to play a key role in early Alzheimer’s is calcineurin, a calcium-dependent serine-threonine phosphatase. Our method repurposes existing drugs to inhibit calcineurin.
Innovation and Meaningful Advantages
Our method can be used to treat early Alzheimer’s disease, as well as to treat and prevent other neurodegenerative disorders. The CsA-type drugs we have identified have all been FDA-approved for treatment of various conditions, including high blood pressure and cancer, but have not yet been used to treat neurodegenerative disorders. These drugs include bromocriptine, Irbesartan, meclizine, nebivolol, rosiglitazone, salmeterol, sorafenib, sulfasalazine, tamoxifen, tetrabenazine, xinafoate, and XLl84.
Drug repurposing is cost-effective and efficient, as existing FDA-approved drugs have already passed clinical trials to evaluate safety. This is a particularly powerful approach for small-molecule treatment of neural disorders, as small molecules are more likely than protein-based biologics to cross the blood-brain barrier.
Through extensive studies using zebrafish larvae as a model system, we have established the effects of calcineurin inhibition on behavior. Subsequent studies could be carried out on mice and other mammals. While the FDA-approved drugs we have identified have already been examined for safety, clinical trials are needed to establish the efficacy of CsA-type drugs in the prevention and treatment of Alzheimer’s disease and other neurodegenerative disorders.
We are interested in exploring 1) startup opportunities with investors in the drug delivery space; 2) research collaborations with leading pharmaceutical companies to develop this treatment; and 3) licensing opportunities for drug delivery companies.
Robert Creton, PhD
Professor of Medical Science (Research)
Professor of Pathology and Laboratory Medicine (Research)
Brown Tech ID #3144
63/193,935; provisional application, filed 5-27-21.
Tucker Edmister, S., Del Rosario Hernández, T., Ibrahim, R. et al. Novel use of FDA-approved drugs identified by cluster analysis of behavioral profiles. Sci Rep 12, 6120 (2022). https://doi.org/10.1038/s41598-022-10133-y
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