You are here

Development of Pirenzepine for CIPN

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA213555-01A1
Agency Tracking Number: R41CA213555
Amount: $298,550.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: O
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-05-23
Award End Date (Contract End Date): 2018-07-31
Small Business Information
4685 CONVOY ST #210, San Diego, CA, 92111-2339
DUNS: 078868444
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 ANDREW MIZISIN
 (858) 336-9084
 amizisin@winsantor.com
Business Contact
 STANLEY KIM
Phone: (858) 336-8094
Email: skim@winsantorbio.com
Research Institution
 UNIVERSITY OF CALIFORNIA SAN DIEGO
 9500 Gilman Drive, Mail Code 0934
LA JOLLA, CA, 92093-0934
 Nonprofit college or university
Abstract
PROJECT SUMMARY Chemotherapy induced peripheral neuropathy CIPN is a debilitating complication that can arise from use of a number of chemotherapeutics and which limits both the dose and duration of cancer treatments with these agents Up to of cancer patients treated with chemotherapy describe some form of CIPN with sensory neuropathy being dominant Symptoms vary from tingling and numbness indicative of sensory loss to aspects of painful neuropathy such as allodynia and spontaneous shooting pains The American Society of Clinical Oncology makes no recommendations for the prevention of CIPN and provides only a moderate recommendation for treatment with duloxetine a serotonin norepinephrine reuptake inhibitor for symptomatic relief of pain WinSanTor s founders have uncovered a new homeostatic mechanism in sensory neurons that constrains mitochondrial function which can be exploited to improve energy supply to reverse and to prevent nerve damage in CIPN We have demonstrated that the muscarinic acetylcholine type receptor M R signaling limits mitochondrial activity and that antagonizing M R increases the overall respiratory capacity of mitochondria Additionally we have observed that the M R antagonist pirenzepine can prevent the neuropathy induced by chemotherapeutic agents The goal of this Phase I STTR project is to assess the therapeutic potential of pirenzepine as a CIPN intervention that enhances neuronal AMPK activity and restores neuronal energy capacity to prevent or reverse neuropathy without impeding the chemotherapeutic microtubule stabilizing properties of paclitaxel To this end our Specific Aims are Specific Aim Assess the tumoricidal activity of paclitaxel in presence of pirenzepine Specific Aim Test efficacy of pirenzepine in mouse paclitaxel models of CIPN The studies proposed herein will advance further pre clinical development of pirenzepine as a potentially first in class therapy for preventing and or reversing CIPN PROJECT SUMMARY Chemotherapy induced peripheral neuropathy CIPN is a debilitating complication that can arise from use of a number of chemotherapeutics and which limits both the dose and duration of cancer treatments with these agents Up to of cancer patients treated with chemotherapy describe some form of CIPN with sensory neuropathy being dominant Symptoms vary from tingling and numbness indicative of sensory loss to aspects of painful neuropathy such as allodynia and spontaneous shooting pains The American Society of Clinical Oncology makes no recommendations for the prevention of CIPN and provides only a moderate recommendation for treatment with duloxetine a serotonin norepinephrine reuptake inhibitor for symptomatic relief of pain WinSanTor s founders have uncovered a new homeostatic mechanism in sensory neurons that constrains mitochondrial function which can be exploited to improve energy supply to reverse and to prevent nerve damage in CIPN We have demonstrated that the muscarinic acetylcholine type receptor M R signaling limits mitochondrial activity and that antagonizing M R increases the overall respiratory capacity of mitochondria Additionally we have observed that the M R antagonist pirenzepine can prevent the neuropathy induced by chemotherapeutic agents The goal of this Phase I STTR project is to assess the therapeutic potential of pirenzepine as a CIPN intervention that enhances neuronal AMPK activity and restores neuronal energy capacity to prevent or reverse neuropathy without impeding the chemotherapeutic microtubule stabilizing properties of paclitaxel To this end our Specific Aims are Specific Aim Assess the tumoricidal activity of paclitaxel in presence of pirenzepine Specific Aim Test efficacy of pirenzepine in mouse paclitaxel models of CIPN The studies proposed herein will advance further pre clinical development of pirenzepine as a potentially first in class therapy for preventing and or reversing CIPN

* Information listed above is at the time of submission. *

US Flag An Official Website of the United States Government