Potential New Therapeutic for Debilitating Pain Associated with Chemotherapy

Results of a new animal study conducted by a University of Iowa team of researchers and published in the Journal of the International Association for the Study of Pain (PAIN), demonstrate that a next-generation form of vitamin B3 called nicotinamide riboside (NR) may be effective at helping to relieve one of the most debilitating neurological side effects of a chemotherapy drug (called paclitaxel) which is commonly used to treat breast and ovarian cancers. Led by Dr. Donna Hammond, Ph.D., the team concluded that NR may represent a new therapeutic approach for the relief of chemotherapy induced peripheral neuropathy (CIPN) in humans.

For many women, the side effects of chemotherapy are often a permanent reminder of their condition. CIPN pain and numbness in the fingers and/or feet is an all-too-common, life-altering side effect of paclitaxel. The condition can sometimes get so severe that patients can’t continue treatment. When that happens, the chemotherapy dose must either be reduced or delayed, which isn’t good for fighting cancer cells.

With the American Society of Clinical Oncology issuing a position statement urging that there is an unmet need for treatments that can alleviate CIPN, they consider the development of therapies for the prevention and relief of CIPN essential for patient care. Following the University of Iowa study, this provides important pre-clinical proof of concept to advance the investigation of NR as a solution to this unmet need.

Dr. Marta Hamity, Ph.D., the lead study author, indicated that the team embarked on the study based on evidence that suggested that increasing levels of a central regulator of cellular metabolism – called NAD+ – in the cells may protect against injury to neurons. NAD+ helps produce the most vital energy at the cellular level which is essential for healthy cellular function and the key to increasing the amount of time spent in good health. 

Given that women represent the mainstay of the population more commonly afflicted with breast, and exclusively afflicted with ovarian cancer, the team thoughtfully designed the study to include female rats. They also incorporated clinically relevant doses of the chemotherapy drug, and measures to assess and quantify the impact of CIPN on quality of life, to try and improve the likelihood that the pre-clinical study results more closely mimic the confounding factors which may influence one’s outcome of success or failure on treatment.

Following the completion of the study, the results confirmed that treatment with NR increased blood levels of nicotinamide adenine dinucleotide (NAD+) by 50 percent after three weeks of daily use.  NR prevented the development of touch hypersensitivity induced by the drug and reversed existing touch hypersensitivity in this rodent model. Furthermore, the preventative effect was sustained for at least two weeks after NR treatment was discontinued.

“This is significant because the pain associated with CIPN can increase as the [chemotherapy] dose escalates, and at times it reaches a point where the patient is no longer able to tolerate the effective doses,” explained Hammond. “This study has provided positive data which is particularly exciting considering the unmet need for therapies in this area. We believe that further development of NR as a therapy for CIPN is warranted.”

Additional research about NR and NAD+ can be found at www.AboutNR.com.

Article by: Amy Boileau, PhD, RD, Director, Scientific Affairs of ChromaDex