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Neuroprotective compound for treating protein misfolding in neurodegenerative diseases

Summary: Neurodegenerative diseases, such as Parkinson’s, Alzheimer’s, and Huntington’s, are characterized by misfolded proteins that aggregate and induce neuronal toxicity and death. Protein disulfide isomerase (PDI) is an enzyme implicated in protein misfolding and has been shown to be upregulated in the brains of patients with neurodegenerative diseases. However, the lack of reversibly-binding, selective inhibitors has limited pharmaceutical options for treating conditions associated with elevated PDI activity. This technology is a small molecule compound that reversibly binds to and inhibits PDI activity. As inhibition of PDI has been shown to have neuroprotective effects, this compound is a promising drug candidate for treatment of neurodegenerative diseases.

Technology Benefits: Inhibition of PDI has neuroprotective effectReversibly binds to PDIHigher affinity to PDI compared to available PDI modulatorsMinimizes toxicity due to non-specific PDI inhibitionPatent Information:Patent Pending (WO/2016/118639)Tech Ventures Reference: IR CU15151

Technology Application: Therapeutic for neurodegenerative conditions related to protein misfoldingTherapeutic for other disorders (e.g. cancer) related to PDI upregulationCreation of PDI-deficient animal models for research

Detailed Technology Description: None

*Abstract: None

*Inquiry: Beth KaudererColumbia Technology VenturesTel: (212) 854-8444Email: TechTransfer@columbia.edu

*IR: cu15151

*Principal Investigator

*Publications: Kaplan A, Gaschler MM, Dunn DE, Colligan R, Brown LM, Palmer AG 3rd, Lo DC, Stockwell BR, “Small molecule-induced oxidation of protein disulfide isomerase is neuroprotective” Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):E2245-52.Hoffstrom BG, Kaplan A, Letso R, Schmid RS, Turmel GJ, Lo DC, Stockwell BR. “Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins” Nat Chem Biol. 2010 Dec;6(12):900-6.

Country/Region: USA

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