New Treatment for Chemotherapy-Induced-Neuropathic Pain

The new year is always a time to look back and reflect on the many achievements of the prior year. I have been pleased that the Fraternal Order of Eagles has committed continued support to a program that will be overseen by the FOEDRC that seeks to develop new treatments for diabetes and its complications and to  bring them ultimately to market. The Bridge to the cure program represents an innovative collaboration and we are excited by what this new year will bring. For this reason, I have chosen to write about one example from a FOEDRC member that recently demonstrated the ability of the compound nicotinamide riboside to restore nerve damage from chemotherapy. We believe that this same mechanism could lead to improved nerve function in people with diabetes. I hope that you will enjoy reading about this exciting advance below.

January 2019

Dr. Charles Brenner’s, Professor & Head of Biochemistry and member of the FOEDRC, group discovered nicotinamide (NR) as an unanticipated vitamin precursor of NAD, the central regulator of metabolism.  They also developed a technology called targeted NAD metabolomics and used it to discover that a number of metabolic stresses attack NAD. Specifically, Brenner’s group have shown that obesity and type 2 diabetes depress an NAD-related molecule called NADPH in the liver, and that heart failure and neuronal (nerve) injury depress NAD in the failing heart and neurons (nerves). They also generally find that under conditions of metabolic stress that the NR pathway—the genes and enzymes that turn NR into NAD and NADPH—are ramped up. This has led to the paradigm that failing tissues need NR to restore their NAD and their metabolic functions, i.e., for the liver to detoxify free radicals, for the heart to beat, and for nerves to transmit sensations and ideas.

Brenner and his collaborators have shown that if they supplement NR into rodent diets, they can very substantially protect animals from fatty liver, diabetic neuropathy, chemotherapeutic neuropathy and heart failure. The technology is protected by multiple patents that were licensed by ChromaDex, a company for which Brenner serves as the chief scientific adviser. There are a number of clinical trials testing NR against diseases and conditions and, in addition, NR has been commercialized as a nutritional supplement called Tru Niagen to promote wellness and resiliency against metabolic stress.

Brenner’s labs’ latest result—a collaboration with Dr. Richard Goodman’s group at Oregon Health Sciences University—was interesting for two reasons. First, they gained insight into what disturbance in the NAD pathway makes a neuron degenerate. Second, they found an unexpected drug combination that could prove to be more powerful than NR for neuroprotection. In short, they found that two compounds related to NR have opposite effects on a damaged neuron. NMN (NR with a phosphate added to it) is neurotoxic while NAR (NR with an oxygen in place of an amino group) is neuroprotective. By combining a drug that blocks NMN formation with NAR, they can get the NR pathway to make NAD and protect the neuron without making the neurotoxic compound NMN. Dr. Brenner’s group understand these pathways pretty well and are confident to be able to evaluate the drug potential of this combination in relatively short order.

Dr. Brenner’s work has been supported in the past with pilot and feasibility funding from the FOEDRC and the present work received new and ongoing supported from the National Institutes of Health and the Roy J. Carver Trust.