2 January DRC Director's Report - January 2019 January 2, 2019 By The Fraternal Order of Eagles Diabetes Research Center 0 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. New Treatment for Chemotherapy-Induced Neuropathic Pain 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. Related Articles DRC Director's Report - March 2019 Brian T. O’Neill, MD, PhD, assistant professor in the Division of Endocrinology in the Department of Internal Medicine and member of the FOEDRC recently published in the journal Diabetes the discovery that FoxO proteins, which are transcription factors that regulate DNA, are the critical regulators of diabetes-related muscle atrophy. DRC Director's Report - April 2019 In a recent study done by Wei Bao, MD, PhD, assistant professor in the Department of Epidemiology and member of the FOEDRC, his research team found that frequent consumption of fried foods, especially fried chicken and fried fish/shellfish, was associated with a higher risk of death from all causes and cardiovascular disease in women in the United States. Women with at least one serving per week of fried chicken had a 13% higher risk of death from all causes, and a 12% higher risk of death from cardiovascular disease, when compared with women with no consumption of fried chicken. DRC Director's Report - January 2021 A recent study by a team of UI researchers led by E. Dale Abel, MD, PhD, Director, FOEDRC discovered eating a ketogenic diet rescued mice from heart failure. The study, published in the November issue of the journal Nature Metabolism, was one of three companion papers from independent research teams that all point to the damaging effects of excess sugar (glucose) and its breakdown products on the heart. The UI study also revealed the potential to mitigate that damage by supplying the heart with alternate fuel sources in the form of high-fat diets. Given its need for a constant, reliable supply of energy, the heart is very flexible about the type of molecules it can burn for fuel. Most of the heart’s energy comes from metabolizing fatty acids, but heart cells can also burn glucose and lactate, and also ketones. DRC Director's Report - December 2019 In individuals with obesity and type 2 diabetes a surplus of energy from too much food or increased glucose and lipids can increase tissue metabolism to damaging rates. This is much like a river overflowing its banks, where water no longer channeled in a controlled way can cause catastrophic damage by being in the wrong places. DRC Director's Report - February 2019 The Department of Defense office of the Congressionally Directed Medical Research Programs has awarded DRC member, Ethan Anderson, Associate Professor College of Pharmacy, funding as part of its Peer Reviewed Medical Research Program (PRMRP) Discovery Award competition. The project is: Exploiting the Paracrine-Like Effect of Prohibitin-1 to Treat Septic Cardiomyopathy. The grant will provide $310,000 in total support over a 2-year period. DRC Director's Report - October 2019 The current epidemic of obesity is a major contributing factor in the rising rate of type 2 diabetes. Recent work from the laboratory of Kamal Rahmouni, PhD, a member of the Fraternal Order of Eagles Diabetes Research Center (FOEDRC), uncovered a novel and important role for a protein complex called the BBSome in the function of key nerve cells called neurons in small a part of the brain known as the hypothalamus that controls food intake, body’s fat and glucose metabolism. Showing 0 Comment Comments are closed.