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Identifying and Optimizing Treatment for Neuropathic Pain

Tabach Yuval, HUJI, School of Medicine - IMRIC, Developmental Biology and Cancer Research

Neuropathic pain- One of our distinctive results which we optimized recently identifies several compounds that we identified as having a potential protective role in neuropathic pain. We pursued this finding in collaboration with the Clinical Pain Innovation Lab at Haifa University, led by Dr. Treister, who is a clinical pain researcher with vast experience in analgesic research/development.  We began validation of one of these compounds in a preclinical study, in which we assessed the compound’s potential analgesic effects in rats using the spared nerve injury model (SNI). The SNI involves ligating the tibial and common peroneal nerve while sparing the sural nerve. Mechanical pressure withdraw thresholds was assessed using Von Frey test, before and after inducing the nerve injury. The study included 6 study arms (n=5 rats in each), including three treatment arms, treated with 50, 100, and 200mg/kg body weight of the compound for five weeks, initiated 3 days post-ligation. Three additional study arms served as controls: (1) a shame control (non-ligated, i.e. were operated but without harming the nerves); (2) control (ligated) and (3) positive control (ligated) receiving imipramine (10mg/kg body weight), a tricyclic antidepressant that is approved for treating NP. As can be seen in Fig 2, the results are exciting: the drug shows statistically significant, dose-dependent, effects. Higher dosages demonstrated better analgesic effects than the positive control. These results prompted us to continue investigating the potential of this drug as a treatment for NP. Taken together, we believe that the overall picture is very supportive in continuation of our efforts to clinically evaluate the compounds efficacy  in treating NP. About 10% of the general population experiences neuropathic pain (NP). Pain caused by damage or disease affecting the nervous system. The number of people experiencing neuropathic pain is constantly increasing due to the growing porportion of cancer and diabetes cases worldwide. Unfortunately, many patients with neuropathic pain do not respond to available treatments, therefore, investing in research and development of effective and improved drugs has huge potential both clinically and commercially.

The genetic revolution that has happened over the recent years brings new opportunities to the field of drug discovery & repositioning. Using advanced comparative genomic, and data integration, Dr. Tabach and his team have been developing a state-of-the-art AI algorithm which maps drug and food supplements useful in treating diseases and improving health conditions. To create this algorithm, we have been integrating and analyzing massive amounts of genomic data from 1,600 genomes, 14 thousand compounds, 20,000 human genes, and a comprehensive database of phenotypic data (figure 1).

Neuropathic pain- One of our distinctive results which we optimized recently identifies several compounds that we identified as having a potential protective role in neuropathic pain. We pursued this finding in collaboration with the Clinical Pain Innovation Lab at Haifa University, led by Dr. Treister, who is a clinical pain researcher with vast experience in analgesic research/development.  We began validation of one of these compounds in a preclinical study, in which we assessed the compound’s potential analgesic effects in rats using the spared nerve injury model (SNI). The SNI involves ligating the tibial and common peroneal nerve while sparing the sural nerve. Mechanical pressure withdraw thresholds was assessed using Von Frey test, before and after inducing the nerve injury. The study included 6 study arms (n=5 rats in each), including three treatment arms, treated with 50, 100, and 200mg/kg body weight of the compound for five weeks, initiated 3 days post-ligation. Three additional study arms served as controls: (1) a shame control (non-ligated, i.e. were operated but without harming the nerves); (2) control (ligated) and (3) positive control (ligated) receiving imipramine (10mg/kg body weight), a tricyclic antidepressant that is approved for treating NP. As can be seen in Fig 2, the results are exciting: the drug shows statistically significant, dose-dependent, effects. Higher dosages demonstrated better analgesic effects than the positive control. These results prompted us to continue investigating the potential of this drug as a treatment for NP. Taken together, we believe that the overall picture is very supportive in continuation of our efforts to clinically evaluate the compounds efficacy  in treating NP.

Therefore, we have currently started an open-label proof-of-concept study to assess the effects of the compound in patients with painful diabetic neuropathy. At this point in time, despite the limited number of participants, we have observed a significant improvement of symptoms, but it is too early to make any conclusions as the study is still ongoing. We plan to continue investigating this compound and continue investigating other candidate compounds that have been identified by our algorithm. 

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Mel Larrosa
VP Business Development Healthcare
+972-2-6586692
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