A newly developed monoclonal antibody, ALT-100, targets and neutralizes a key protein involved in inflammation, offering potential treatment options for preterm births and fatty liver disease, both of which currently have limited solutions. By focusing on a master-regulator protein of inflammation, eNAMPT, this treatment has shown promise in reducing the severity of diseases that are driven by excessive inflammation.
Dr. Joe G.N. “Skip” Garcia from UF Health explained that uncontrolled inflammation is a major factor in the severity of various diseases, including preterm births due to uterine infections and non-alcoholic fatty liver disease associated with obesity. According to him, “Combined with our earlier studies, these results suggest that stopping the inflammatory cascade may prevent disease progression for a wide range of serious conditions with limited options, including the heartbreak of preterm birth and the difficult, protracted cascade of illnesses that flow from fatty liver disease including cirrhosis and liver cancer.”
ALT-100, an antibody developed by Dr. Garcia’s group, neutralizes eNAMPT, a protein that controls inflammation. Excessive amounts of eNAMPT can lead to severe inflammation, organ damage, and even a cytokine storm which was a major cause of COVID-19 deaths. Garcia mentions, “The eNAMPT protein may be the most important factor in amplifying the innate immune response. When eNAMPT regulation is impaired, the results are potentially disastrous.”
In studies, ALT-100 showed promising results in preventing preterm births. High levels of eNAMPT were found in blood and tissues from women who experienced preterm births. Dr. Garcia said, “In these mice, 80% of the babies were dead on delivery. With our antibody, 80% were alive,” adding that eNAMPT is a “highly druggable target” involved in complications of premature births.
In fatty liver disease, which affects a quarter of adults and can lead to liver cancer, ALT-100 also exhibited positive outcomes. “Inflammation plays a serious role in the transition from fatty liver to liver fibrosis, cirrhosis and liver cancer,” Garcia stated. The ALT-100 antibody might be a precise way to combat this.
ALT-100 works by blocking eNAMPT, which activates an inflammatory cascade through toll-like receptor 4 (TLR4). By targeting eNAMPT instead of TLR4 directly, ALT-100 allows TLR4 to continue protecting against infections.
The antibody has passed initial safety trials in humans and is about to be tested for acute respiratory distress syndrome. Furthermore, it might be effective against autoimmune diseases and cancer.
Dr. Garcia concludes, “I believe that our antibody is a highly novel and potentially impactful tool to address multiple serious unmet needs around the world. It will be gratifying to validate this hope in our upcoming clinical trials.”
