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Development of KLS-13019 for Chemotherapy Induced Peripheral Neuropathy and Drug Dependence

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41DA044898-01
Agency Tracking Number: R41DA044898
Amount: $299,916.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIDA
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-01-01
Award End Date (Contract End Date): 2019-12-31
Small Business Information
4 KNOLL CT
Lloyd Harbor, NY 11743-9731
United States
DUNS: 968773643
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 SARA WARD
 (215) 707-1005
 saraward@temple.edu
Business Contact
 KATHLEEN CZUPICH
Phone: (215) 489-4944
Email: kczupich@artemis-finance.com
Research Institution
 TEMPLE UNIV OF THE COMMONWEALTH
 
1801 N BROAD STREET, 401 CONWELL HALL
PHILADELPHIA, PA 19122-6003
United States

 Nonprofit College or University
Abstract

Chemotherapy induced peripheral neuropathyCIPNcan be a chronicseverely debilitating consequence of
cancer therapy for which there are no effective management strategiesMoreoverupwards ofof CIPN
patients reported using prescription opioids for pain management despite the fact that there is only weak
evidence that long term continuation of opioids provides clinically significant pain relief in these patientsMitochondrial dysfunctionoxidative stressand inflammation have all been implicated in its etiologyWe have
shown that the non psychoactive cannabinoid cannabidiolCBDprevents the development of CIPN in a
mouse model of paclitaxel induced cold and mechanical allodyniaIn vitrowe observe that paclitaxel
increases microglial expression of several putative mediators of neuropathic painand that this effect can be
blocked by CBD in a mitochondrial NaCaexchangermNCXdependent mannerWe have also recently
shown that a more potenthydrophilic analogue of CBDKLSprotects against paclitaxel induced
oxidative stress in cultured dorsal root ganglia neuronsand that the mechanism underlying this
neuroprotection is also regulation of intracellular calcium via the mNCXPreliminary results demonstrate that
KLScan attenuate mechanical sensitivity associated with CIPN while also reducing microglial activation
and T cell infiltration into the spinal cordOur central hypothesis is that administration of CBD or KLShelps preserve Cahomeostasis by promoting activity of the mNCXwhich in turn protects from both
mitochondrial dysfunction and microglial activation to prevent the neuronal and glial changes associated with
the development and maintenance of paclitaxel induced neuropathic painResults from experiments in AIMwill demonstrate that the neuroprotective properties of CBD and KLScan be reduced by
pharmacological or gene knockdown of the mNCX in a statistically significant mannerResults from
experiments in AIMwill further confirm the i pand p oefficacy of KLSvs CBD to prevent or reverse
mechanical sensitivity and neuroinflammation in a mouse model of paclitaxel induced neuropathic pain and
that repeated administration of these compounds does not lead to analgesic toleranceRemarkablythe nonpsychoactive CBD has also been shown to inhibit cue induced heroin seeking and neurochemical correlates
thereof in a rat model of relapse and decrease heroin craving in a small human studyExperiments in AIMare designed to test the hypothesis that KLSand CBD will attenuate reinstatement of morphine seeking
behavior in a rat model of opioid relapseThe overall impact of the results from the proposed research will be
significant advancements intoidentification of specific mechanisms that induce CIPNapplication of this
knowledge to facilitate design of novel treatment strategies for neuropathic painandnovel treatment
strategies to reduce or replace prescription opioid use and decrease prescription opioid abuse Chemotherapy induced peripheral neuropathyCIPNcan be a chronicseverely debilitating
consequence of cancer therapy for which there are no effective management strategiesMoreoverupwards ofof CIPN patients reported using prescription opioids for pain
managementdespite the weak evidence of their efficacy and the risks of long term
dependenceMitochondrial dysfunctioncalcium dysregulationoxidative stressand
inflammation have all been implicated in its etiologyCannabidiolCBDis a non psychoactive
component of Cannabis sativa is effective in both treating CIPN and relieving opiate
dependenceHoweverCBD has severe limitations in terms of potencysafetyoral
bioavailabilityand regulatory restrictionsKannalife has solved these problems in its patented
series of derivatives that include KLSThis grant will demonstrate the efficacy of KLSin models of CIPN and opiate dependenceand will further elucidate its mechanism of
action in regulation of calcium levels and inflammatory sequelae

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

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