Excess bile acids entering the colon contribute to the symptoms of bile acid malabsorption (BAM) which is characterized by excess fecal bile acids and chronic watery diarrhea. BAM is often misdiagnosed as diarrhea-predominant irritable bowel syndrome (IBS-D) and is considered responsible for 30-50% of unexplained chronic diarrhea.
Although BAM can be attributed to ileal damage or rare apical sodium-dependent bile acid transporter (ASBT) mutations, the cause of most cases of idiopathic BAM is unknown. Recent advances in understanding this disease suggest that overproduction of bile acids resulting from deficient fibroblast growth factor (FGF)-19 may be a common feature of BAM. FGF19 is part of the mechanism for feedback inhibition of hepatic bile acid synthesis from cholesterol, and regulation of bile acid synthesis is impaired in its absence. This dysregulation leads to hepatic overproduction of bile acids, exceeding the ileal absorptive capacity, thereby increasing colonic exposure and diarrhea.
In the US, the diagnosis of BAM is limited by the lack of sensitive, specific and cost-effective tests. Current methods are time-consuming, difficult, not readily available, or not validated clinically. Hence, BAM is often diagnosed by administering bile acid sequestrants, such as colesevelam, in a therapeutic trial, an approach that lacks specificity and has a high rate of false-negative results.
In response, VA researchers have developed an imaging probe having the ability to non-invasively assess bile acid transport and diagnose impaired intestinal bile acid uptake, such as BAM, while not being susceptible to bacterial degradation.
The probe is a trifluorinated bile acid analogue (CA-sar-TFMA) which exhibits in vitro stability and affinity for ASBT. A pilot in vivo disposition study in mice confirmed that CA-sar-TFMA can be imaged in the gallbladder using 19F MRI. Resistance to bacterial deconjugation diminishes the potential for intestinal microbiota to alter probe concentrations in the enterohepatic circulation and also increases the half-life of the fluorinated bile acid analogue probe.
- CA-sar-TFMA imaging probe may be administered orally or by gastric lavage with retention of image enhancement properties
- Businesses can develop products from the research by licensing US patent 9,597,417 from the VA
- VA license fees are negotiable
- TechLink guides businesses through licensing at no charge
- VA ID: 14-015