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Bcl-w Prevents Chemotherapy-Induced Peripheral Neuropathy

The first treatment and prevention mechanism using Bcl-w proteins, BH4 domain-containing fragments or Bcl-w mimetics

  • Therapeutics

Project Overview

  • Axonal degeneration impairs circuit functionality and is a prominent component of multiple neurologic disorders.
  • Many chemotherapeutic drugs required to treat cancers have been found to injure long-range axons causing chemotherapy-induced peripheral neuropathy (CIPN).
  • Scientists at Dana-Farber have discovered the first treatment and prevention mechanism for CIPN.
  • Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing these assets for further development. 

Technology

Dana-Farber researchers have discovered that treatment or prevention of CIPN or hearing loss can be achieved using Bcl-w proteins, BH4 domain-containing fragments or Bcl-w mimetics. By using compartmented cultures, they demonstrated that chemotherapeutic drugs reduce axonal levels of Bcl-w, the anti-apoptotic Bcl-2 family member that promotes axonal survival and maintenance, pointing to a mechanism for preventing and treating CIPN. 

To identify anti-apoptotic Bcl2 family members that protect axons from the degeneration effects of paclitaxel (common chemotherapy medication), protein transfection was used in compartmented cultures to overexpress recombinant Bcl-w in axons. Transfected axonal Bcl-w completely prevented paclitaxel-induced axonal degeneration in neuronal cell cultures as well as in vivo in mice models injected with paclitaxel. Moreover, Bcl-w was shown to partially prevent paclitaxel-induced loss of innervation in mice models. These data demonstrate that Bcl-w acts locally in axons to prevent degeneration. Furthermore, by restoring Bcl-w protein locally in axons, chemotherapy induced degeneration can be prevented. 

This technology provides compositions and methods for the treatment or prevention of CIPN, including exemplary Bcl-w mimetics and Bclw- BH4 SAHB peptides that are used to prevent and treat CIPN in mouse models. 

Further Details: 

Benefits:

  • Exemplary Bcl-w mimetics and Bclw- BH4 SAHB peptides are provided. 
  • Bcl-w mimetics treat nerve damage caused by CIPN. 
  • Bcl-w mimetics given to patients can help prevent CIPN. 
  • Mice lacking Bcl-w have more severe CIPN when treated with paclitaxel compared to mice with Bcl-w. 
  • Bcl-w protects axons through modulation of IP3R1 and BAX. 

Team Members: Rosalind Segal, MD, PhD, Maria Pazyra-Murphy, MS, Gregory Bird, PhD, Lisa Goodrich, PhD, Loren Walensky, MD, PhD, Sarah Pease-Raissi, PhD

Applications

This technology provides the first treatment and prevention mechanism for CIPN.

Opportunities

Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing these assets for further development. 

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Team Members