Irritable bowel syndrome (IBS) is a gastrointestinal (GI) syndrome characterized by chronic
abdominal pain and altered bowel habits in the absence of any organic cause. The symptoms of
IBS not only adversely affect a patient's health-related quality of life (QoL), but also
place a significant financial burden on society due to reduced work productivity and
increased use of healthcare-related resources. Patients with IBS frequently complain of
abdominal bloating and increased gas production in the form of flatulence or belching. The
prevalence in North America and Europe is approximately 10-15%. Irritable bowel syndrome
affects all ages and genders however there is a 2:1 female predominance in North America.
Irritable bowel syndrome is classified into 4 subtypes based on stool pattern: IBS with
constipation (IBS-C), IBS with diarrhea, mixed IBS, and un-subtyped IBS. Irritable bowel
syndrome with constipation is defined as the presence of hard or lumpy stools with ≥ 25
percent of bowel movements and loose or watery stools with < 25% of bowel movements.
SYN-010 is a modified release, oral formulation of lovastatin being developed for the
treatment of IBS-C. The SYN-010 program is based predominantly on research by Dr. Mark
Pimentel and collaborators hypothesizing that reduction in intestinal methane (methane)
production can reverse constipation and improve global symptoms in IBS-C. Methane production
in humans is due to methanogenic archaea in the intestine, predominantly Methanobrevibacter
smithii (M. smithii). Methane, the key product of anaerobic respiration of methanogens, had
been perceived to produce no ill effects in humans aside from gaseous distention. However,
several research groups worldwide have shown that a significant percentage of patients with
IBS-C excrete methane, and elevated methane production by methanogens correlates with
constipation and related symptoms in both IBS-C and chronic idiopathic constipation. A direct
causative role for methane in IBS-C was demonstrated in a recent case report, wherein a woman
undergoing fecal microbiota transplantation (FMT) for C. difficile infection unknowingly
received stool containing a high concentration of methanogens. The FMT recipient rapidly
developed severe symptoms of IBS-C that were subsequently reversed by ablation of methane
production.