Targeting Delta-2 tubulin for the treatment of peripheral neuropathy

This technology identifies several pathogenic roles for Delta-2-tubulin (D2) in chemotherapy-induced peripheral neuropathy that can be used as a therapeutic target.

Unmet Need: Therapeutic options for chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication associated with chemotherapy, and multiple classes of anticancer drugs acting through different antineoplastic mechanisms can induce it. The pathogenesis of CIPN remains largely unknown, and current therapies, such as opioid analgesics, antidepressants, and anticonvulsants, provide only limited symptomatic relief. As a result, there is a critical need to identify therapeutic targets for the prevention and treatment of CIPN.

The Technology: Therapeutic targeting of Delta-2-tubulin in chemotherapy-induced peripheral neuropathy

This technology identifies multiple cellular perturbations resulting from the accumulation of Delta-2-tubulin (D2), an irreversible modification of α-tubulin, in sensory neurons. In preclinical models of chemotherapy-induced peripheral neuropathy (CIPN), overexpression of D2 was found to suppress mitochondrial respiration, inhibit transient receptor potential (TRP) channel function, and upregulate the mitochondrial anchor syntaphilin, in addition to directly impairing axonal mitochondrial motility. Collectively, these alterations contribute to sensory neuron axonopathy. Thus, this technology enables the targeted modulation of specific pathogenetic mechanisms underlying CIPN.

This technology has been validated in vivo with mouse models of CIPN.

Applications:

Treatment of CIPN
Therapy for inherited or acquired peripheral neuropathies
Research tool for analysis of mechanisms driving CIPN

Advantages:

Specific pathogenic mechanisms for CIPN treatment
Shared pathways across various classes of anticancer drugs
Multiple actionable targets
Potential first-in-class therapy

Lead Inventor:

Francesca Bartolini, Ph.D.

Patent Information:

Patent Pending

Related Publications:

Pero ME, Meregalli C, Qu X, Shin GJ, Kumar A, Shorey M, Rolls MM, Tanji K, Brannagan TH, Alberti P, Fumagalli G, Monza L, Grueber WB, Cavaletti G, Bartolini F. “Pathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy.” Proc Natl Acad Sci U S A. 2021 Jan 26;118(4):e2012685118.

Tech Ventures Reference:

IR CU25119, CU18162
Licensing Contact: Kristin Neuman