Columbia Technology Ventures

Specific inhibition of caspase-2 activation for the treatment of neurodegenerative diseases

This technology is a membrane-permeable hexapeptide that specifically inhibits caspase-2 signaling in the central nervous system to treat neurodegenerative diseases.

Unmet Need: Specific inhibition of caspase-2 signaling in the central nervous system

Caspase-2 is an enzyme that is required for many neuronal death pathways, including those implicated in Alzheimer’s disease and other neurodegenerative diseases, making it a promising therapeutic target. However, current caspase-2 inhibitors are not target specific and may cause unwanted side effects by suppressing multiple cellular signaling components. In addition, many therapeutic agents, particularly oligopeptides, suffer from poor cell membrane penetration that reduces their efficacy. As such, there is a need for a highly-specific, membrane-penetrable caspase-2 inhibitor for the treatment of neurodegenerative diseases.

The Technology: Membrane-penetrable Caspase-2 inhibitor prevents caspase-2-mediated cell death

This technology is a hexapeptide that prevents caspase-2 activation by blocking the interaction of caspase‐2 and RAIDD, an essential adapter protein. By preventing the formation of the caspase-2-RAIDD complex, the hexapeptide blocks caspase-2-mediated cell death. Unlike existing caspase-2 inhibitors, this technology is highly specific for caspase-2, which reduces unwanted side effects. In addition, the hexapeptide can be conjugated to a variety of cell-penetrating peptides for improved therapeutic delivery to the central nervous system.

This technology has been shown to prevent the formation of the caspase-2-RAIDD complex in vitro, and is currently being tested in an Alzheimer’s disease murine model.

Applications:

  • Treatment of neurodegenerative diseases, including Alzheimer’s disease, mild cognitive impairment Parkinson’s disease, Huntington’s chorea, amyotrophic lateral sclerosis, and Creutzfeld-Jacob disease
  • Research tool for understanding the role of caspase-2 and RAIDD in cellular signaling

Advantages:

  • Specifically inhibits caspase-2 signaling
  • Does not interfere with other cellular pathways in the brain
  • Penetrates cell membranes for enhanced drug delivery

Lead Inventor:

Carol M. Troy, M.D., Ph.D.

Patent Information:

Patent Issued

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