Lead compound exhibits protective effects in inflammatory colitis, modulates gut microbiome and extends lifespan in C elegans.

Pan-Biome Pharmaceuticals, a Vancouver based preclinical biopharmaceutical company focused on age-related diseases and extending human healthspan, has announced today that its lead compound exhibited protective effects in a preclinical model of inflammatory colitis.

Longevity.Technology: While colitis doesn’t usually have a direct impact on life expectancy, colitis-associated comorbidity does, and colitis can also contribute to bone loss and joint inflammation and increase the risk of blood clots and colon cancer. Moreover, there is a significant link between colitis and the gut microbiome, which plays a crucial role in maintaining a healthy immune system and preventing disease. Dysbiosis of the gut microbiome in people with colitis can lead to inflammation and damage to the intestinal lining, exacerbating symptoms and increasing the risk of associated comorbidities.

The health of the gut microbiome is closely linked to overall healthspan; an unhealthy gut microbiome has been linked to an increased risk of chronic diseases, including obesity, diabetes, cardiovascular disease and cancer, whereas in contrast, a healthy gut microbiome can help maintain a healthy weight, improve nutrient absorption and reduce inflammation, all of which can contribute to a longer and healthier life. Being able to modulate the gut microbiome will help to foster far more positive outcomes.

Dr Andy Sham, PhD, Pan-Biome Scientific Advisor and project manager for the Gut4Health Microbiome Core at BC Children’s Hospital Research Institute said: “Our team has conducted extensive testing of this compound through numerous in vitro and in vivo studies. We have found that the compound demonstrates selective antimicrobial activity and has the ability to modulate the gut microbiome in mice.

“In our most recent study, we observed that the lead compound is well-tolerated when administered orally and provides protective effects in a dextran sulfate sodium-induced mouse model of colitis.”

Recent studies show clear differences between the gut microbiome composition in healthy people versus those with Parkinson’s and Alzheimer’s disease, with altered gut microbiota contributing to inflammation in the body that may spread to the brain.

Most age-related diseases are accompanied by chronic low-grade inflammation (also called inflammaging), resulting in higher levels of pro-inflammatory cytokines in the bloodstream. Pan-Biome’s lead compound activates anti-inflammatory cytokine IL-10 and inhibits the major pro-inflammatory cytokines TNF-a, IL-1b,and IL-6. These cytokines contribute significantly to inflammaging in healthy elderly individuals while also playing a major role in age-related diseases such as rheumatoid arthritis, heart disease, diabetes and Alzheimer’s disease and Parkinson’s disease.

According to the National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), six in ten adults in the US have a chronic disease and four in ten adults have two or more [1].

Pan-Biome’s compound also strongly activates expression of Nrf2and AMPK, which drive signalling pathways that play an important role in delaying aging and lifespan regulation. A decrease in AMPK and NRF2 activity is associated with many age-related diseases. The compound also significantly extended lifespan in the nematode C elegans, one of the most popular biological models for the study of pathways regulating aging and longevity.

Pan-Biome CSO Dr Poul Sorensen: “While we are still working out the mechanism, our compound most likely optimizes mitochondrial functionality. We believe that what we are seeing is part of a common mechanism linking age-related diseases, and we intend to show the efficacy of our multi-target therapy over a wide array of such diseases.”

Pan-Biome CEO Gordon Eberwein added: “Our compound is modulating important pathways that begin to change as we age. By targeting those cytokines involved in chronic inflammation, and by activating those master regulators of metabolism and oxidative stress that play such a key role in aging, we believe that our compound, along with regular exercise and a healthy diet, can play a significant role in extending human healthspan.”

[1] https://www.cdc.gov/chronicdisease/resources/infographic/chronic-diseases.htm