10552204_mlOur Science – Disease Management

There is no cure for celiac disease

The only recourse to recovery for individuals suffering from celiac disease (CD) is a life-long adherence to a gluten-free diet (GFD). However, a majority of individuals with CD do not appear to recover well under a GFD. Furthermore, there is still no effective means for monitoring the intestinal health of a recovering celiac other than an invasive biopsy and even that method is prone to interpretive analysis. This problem is particularly acute in the United States where recent studies have shown that more than 50% of adult celiac patients have persistent villous atrophy.

Non-invasive diagnostic of celiac disease recovery

For disease management we are extending and commercializing a successful clinical study for a metabolic marker compound that can measure the state of recovery of a celiac patient undergoing a GFD. This is a unique capability for which there are no other effective diagnostics.

In this test (referred to as CypCel), a single oral dose of the widely used cholesterol-lowering agent, simvastatin (SV), is administered to a patient. The serum concentration of SV is then measured as an indicator of the health of the intestinal epithelium resulting from adherence to a GFD. CypCel is based on the insight that SV is principally metabolized by cytochrome P450 monooxygenase 3A4 (CYP3A4) in the small intestinal epithelium. Because intestinal inflammation results in reduced CYP3A4 activity in the epithelium, the serum concentration of SV correlates with the recovery of a CD patient. A preliminary clinical study in CD patients demonstrated the proof of concept that CypCel was markedly more effective at detecting subclinical disease in treated CD patients than other serum markers that have been investigated in recent years, including anti-TG2 IgA, anti-DGP IgA, and intestinal fatty acid binding protein (I-FABP). CypCel has potentially huge implications for post-diagnostic management of CD for which methods do not currently exist.

ImmunogenX is collaborating with leading celiac disease centers and clinicians on a Phase II clinical study that will greatly expand the population base of the initial Phase I study and further optimize on the administration of the intestinal marker, better correlate to individual characteristics, and further improve on the metabolic analysis.