Why NAD+ Could Become a New Multiple Sclerosis Therapy

A new study entitled “NAD⁺ protects against EAE by regulating CD4⁺ T-cell differentiation” published in October issue of Nature Communications reports that NAD⁺ can be a future therapeutic drug to treat Multiple Sclerosis.

Multiple sclerosis (MS) is a type of autoimmune disease where the inner layer of nerve cells is damaged by the immune system. This exacerbated reaction against healthy cells is the underlying cause of autoimmune diseases, including MS, but also Type 1 diabetes, lupus, and rheumatoid arthritis.

Now, the team of researchers at the Brigham and Women’s Hospital, and Harvard Medical School found a new molecule that can protect against MS in a mouse model for MS. The molecule in question is nicotinamide adenine dinucleotide (NAD+), a molecule found in all living cells that has the ability to restore immune homeostasis and induce regeneration of damaged cells, thus reverting disease progression.

The authors used mice with experimental autoimmune encephalomyelitis (EAE), the mouse model for human MS most commonly used. When administered to these mice, NAD+ could regulate how CD4+ T cells, a type of immune cell, differentiate. Moreover, the authors found NAD+ promotes the production of two important immunosuppressive cytokines, IL-10 and TGF-b1, which were previously shown to protect from EAE. CD4+ T cells differentiated in vitro in the presence of NAD+ significantly delayed the onset of the disease as well as its severity.

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Stefan G. Tullius, MD, PhD, BWH Chief of Transplant Surgery and Director of Transplantation Surgery Research, and study first author noted, “This is a universal molecule that can potentially treat not only autoimmune diseases, but other acute or chronic conditions such as allergy, chronic obstructive pulmonary disease, sepsis and immunodeficiency.”

Now the researchers are further investigating additional signaling pathways and designing the future potential of NAD+ as a new therapeutic drug for autoimmune diseases.

Abdallah ElKhal, the study;s lead author, commented, “Since this is a natural molecule found in all living cells, including our body, we hope that it will be well-tolerated by patients. Thus, we hope that its potential as a powerful therapeutic agent for the treatment of autoimmune diseases will facilitate its use in future clinical trials.”