Pasadena-based Huntington Medical Research Institutes (HMRI), a pioneer in scientific research dedicated to unraveling diseases of the heart and brain, has gained new insights into a groundbreaking, novel treatment for septic shock using a natural compound found in all living cells, nicotinamide adenine dinucleotide (NAD+), in a study led by immunologist Abdala Elkhal, PhD, assistant professor, and head of the Neuro-Cardio- Immunology Laboratory.
Currently, there are no pharmaceutical drugs capable of preventing septic shock, according to Dr. Elkhal.
Sepsis is characterized by a systemic inflammatory response (SIRS) driven by host cells following systemic bacterial and viral infections – a dysregulated immune response to infection. An excessive inflammatory response can trigger septic shock, resulting in multiple organ failure, including cardiovascular failure, which is the leading cause of death in intensive care units.
Sepsis affects more than 1.7 million people in the US and is the third leading cause of death in US hospitals, accounting for 270,000 deaths annually. Patients who suffer from chronic medical conditions – neurological disorders, cancers, lung and kidney disease are the most vulnerable to Sepsis.
Findings from Elkhal’s research show that NAD+ prevents septic shock in pre-clinical models, protecting from lethal bacterial infections and endotoxic shock. Researchers investigated whether NAD+ protects against bacterial infection by reducing or alleviating the systemic inflammatory response. For septic shock to occur, non-canonical inflammasomes must be activated, creating a pro-inflammatory cytokine storm.
This study, “NAD+ prevents septic shock-induced death by non-canonical inflammasome blockade and IL-10 cytokine production in macrophages,” published in the journal E-Life, showed that treatment with NAD+ protected against endotoxic shock by blocking the non-canonical inflammasome. More importantly, the administration of NAD+ improved survival (up to 80%), and some models showed resistance to septic shock (via the IL-10 signaling pathway, independent from the non-canonical inflammasome).
“Our findings have uncovered a new mechanism impacting both innate and adaptive immunity. The precise and complex processes through which NAD+ mediates immunosuppression while also preventing lethal infections and sepsis-induced death are novel and intriguing,” said Elkhal. “This is especially surprising given that these diseases elicit opposing immune responses and require vastly different treatments. Much more research is needed to fully understand how NAD+ operates in this context.”
While serving on the faculty of Harvard Medical School a decade ago, Elkhal initiated his pioneering work on the coenzyme NAD+, studying its role in regulating the immune system. Through preclinical trials, he observed that NAD+ exhibited significant therapeutic potential for individuals suffering from autoimmune disorders, bacterial infections, and organ transplants. He joined HMRI in December 2022 and has since connected NAD+ to the institutes’ research on the heart and brain.
Elkhal collaborated with Anju Vasudevan and Amina Ghouzlani, HMRI; Cetina Biefer, Hector Rodriguez, Rachid El Fatimy, and Jasper Iske, Brigham and Women’s Hospital, Harvard Medical School; Siawosh K. Eskandari, University of Groningen; Yeqi Nian, Germany Heart Center Berlin and Nanki University.
Based in Pasadena, Huntington Medical Research Institutes (HMRI) is a pioneer in scientific research with a 70-year track record of groundbreaking discoveries that have changed the world – from seatbelts to lifesaving diagnostic technology like the MRI.
Today, HRMI is laser-focused on biomedical research that investigates diseases of the heart and brain, and is committed to inspiring and educating the next generation of scientists.
