Estimates from the National Center for Health Statistics suggest that about 2-5% of the US population has nonalcoholic steatohepatitis (NASH), and an additional 10-20% gave fat accumulation in the liver-or fatty liver. It is projected that NASH will surpass hepatitis C and becoming the leading cause of liver transplant by the year 2020. The exact cause of NASH is not clear but it often occurs in people who are overweight/obese or have other metabolic conditions such as type 2 diabetes or elevated lipids. As NASH progresses it can lead to liver cirrhosis and death. Currently there are no approved treatments for NASH.
Inflammatory Bowel Disease
Inflammatory Bowel Disease (IBD) is a chronic and debilitating condition that results from severe inflammation of the gastrointestinal tract. Two conditions, ulcerative colitis and Crohn's disease, account for the vast majority of the 5 million IBD cases worldwide.
A growing body of scientific evidence suggest a causal link between the gut microbiome and IBD. A number of theories have been proposed implicating the microbiome in the pathogenesis of IBD. Ranging from the activation of the inflammasome through opportunistic pathogens that take advantage of barrier dysfunction to genetic defects within the host that trigger a deleterious response to normally commensal microbiota, the microbiome is central to the development of chronic intestinal inflammation and subsequent IBD.
Second Genome is actively investigating microbially-mediated mechanisms underlying IBD. By identifying the bacteria and viruses that play a role in IBD, our research team is aiming to identify new therapeutic approaches and strategies to treating this debilitating condition.
A significant body of research suggests that the microbiome is causal in the development of numerous metabolic disorders, including obesity and type 2 diabetes.
The worldwide prevalence of obesity and associated metabolic conditions continues to increase rapidly, impacting more than one in 5 Americans. Emerging evidence suggests that the microbiome is central to metabolic processes and redefines the way we understand this disease and its progression. Recent microbiome transplant studies have demonstrated that the introduction of specific microbes can influence host biology to drive weight loss or gain, suggesting the microbiome is an untapped source for the treatment of obesity. Leveraging our novel drug discovery platform, Second Genome can understand the unique biological interplay between the host and microbiomes to identify potential therapeutic targets to help curb the metabolic disease epidemic.
The link between the gut flora and a wide variety of diseases is beginning to be appreciated. Recent interest in the immunomodulatory roles of particular bacterial species within the gut has been highlighted in murine model systems of melanoma. These studies have shown that the effect of the immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-L1) depend on Bacteroides and Bifidobacterium species subsets in these murine systems. In humans suffering from melanoma, the therapies that generate the most durable responses activate the immune system, but only in a fraction of patients. Recent survival success of the immune checkpoint inhibitors targeting CTLA-4 and the PD-1/PD-L1 axis in patients with melanoma, along with the murine data, suggests that certain microbial flora could predict responses to these therapies and offer novel therapeutic avenues.
As an initial discovery step we are profiling the gut microbiome in advanced stage cancer patients before, during and after immune targeting therapies to predict patient response to therapy as well as identify microbial flora that predispose patients to autoimmune side effects. We believe this information can help better identify patients for these expensive therapies and can lead to identification of key taxa, metabolites, proteins and peptides that may be therapeutic agents to use in conjunction with checkpoint inhibitors to enhance their overall efficacy.
Central Nervous System Disorders
Recent research has demonstrated a strong link between CNS disorders and the gut microbiome. Our initial project is focused on autism spectrum disorders (ASD). While ASD hs a strong genetic component, it is also believed that the gut microbiome may play a role in the condition. Several studies have examined the gut microbiomes of individuals with autism and support the idea of a strong link between the human microbiome and autism-related behaviors.Second Genome was recently awarded a $2.1M fast-track NIH grant to expand the SG Technology Platform to develop treatments for central nervous system disorders to support the M3 program.