A new pathway discovered regulating autoimmune diseases

The main function of the immune system is to protect against diseases and infections. For unknown reasons our immune system attacks healthy cells, tissues and organs in a process called autoimmunity, which can result in diseases such as multiple sclerosis, type 1 diabetes, lupus or rheumatoid arthritis. There are currently no existing cures for these diseases.

Now, in a new study by researchers at Brigham and Women's Hospital (BWH), a potential treatment maybe on the horizon. Researchers found that NAD+, a natural molecule found in living cells, plants and food protects against autoimmune diseases by altering the immune response and turning “destructive” cells into “protective” cells. The molecule is also able to reverse disease progression by restoring damaged tissue caused by the autoimmunity process.

“Our study is the first to show that NAD+ can tune the immune response and restore tissue integrity by activating stem cells,” said Abdallah ElKhal, PhD, BWH Division of Transplant Surgery and Transplantation Surgery Research Laboratory, senior study author. “These findings are very novel and may serve for the development of novel therapeutics.”

The study is published online October 7, 2014 in Nature Communications.

The scientists performed pre-clinical trials using experimental autoimmune encephalomyelitis, a pre-clinical model for human multiple sclerosis. They showed that NAD+ can block acute or chronic inflammation by regulating how immune cells, called CD4+ T cells, differentiate. Mice receiving CD4+ T cells along with NAD+ present had a significant delayed onset of disease, as well as a less severe form, therefore demonstrating the molecule's protective properties.

“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,” said Stefan G. Tullius, MD, PhD, BWH Chief of Transplant Surgery and Director of Transplantation Surgery Research, lead study author.

Moreover, the researchers demonstrated that NAD+ can restore tissue integrity which may benefit patients that have advanced tissue damage caused by autoimmune diseases. In terms of next steps, ElKhal notes that the lab is currently testing additional pathways and the clinical potential of NAD+.

“Since this is a natural molecule found in all living cells, including our body, we hope that it will be well-tolerated by patients,” said ElKhal. “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.”

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The Transplant Surgery Research Laboratory and Dr. ElKhal's work is supported by the National Institutes of Health and the Slim Foundation.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in Massachusetts and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $650 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation's first full face transplant in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information, resources and to follow us on social media, please visit BWH's online newsroom.