UC San Diego

Neurodegenerative diseases are characterized by loss of sensory neurons leading to motor, cognitive, and memory deficits. Due to the lack of a cure for such diseases, these diseases are costly in the United States. Extensive studies in the past showed the potential of nerve growth factor (NGF) as a therapeutic measure due to its trophic capabilities affecting the proliferation and regeneration of neurons. Therefore, NGF has been tried in several clinical trials, but all failed because of painful side effects such as site injection hyperalgesia or myalgia. However, the recent discovery of a mutant NGF (NGFR100W) that does not induce pain allowed us to investigate its potential as an alternative. Due to the blood-brain barrier limiting the administration of these NGF, we explored the effect of NGFR100W by injecting it into CharcotMarie Tooth Type 2B mouse models as they closely resemble peripheral neuropathy. We performed a hot plate test for nociception and sensitivity of the peripheral nerves by injecting increasing doses of NGFR100W. NGFR100W injected groups did not show significant pain perception compared to wild-type NGF injected groups even in high doses. Our immunohistochemistry data further indicated that NGFR100W prompted neuronal recovery comparable to that observed in wild-type NGF. We also explored the regenerative aspect of NGFR100W which rescued the sensory perception of the CMT2B mouse. Based on these findings, we validated the capability of NGFR100W in regenerating neurons and sensory function, which can be potentially used to improve the condition of individuals with peripheral neuropathy.