MB-102(Mustang Bio, Inc.)

Accurate assessment of kidney function is essential for diagnosing and managing chronic kidney disease (CKD) and acute kidney injury (AKI), adjusting drug dosages, and predicting clinical outcomes. Despite its ubiquitous use, serum creatinine has significant limitations, necessitating the exploration of alternative and complementary biomarkers and technologies. This review revisits the benefits and limitations of serum creatinine, explores other kidney function biomarkers such as Cystatin C and ProEnkephalin, and examines traditional gold-standard techniques, including creatinine clearance, radioisotopes, and inulin clearance. Furthermore, it highlights innovations in real-time glomerular filtration rate (GFR) measurement, such as transdermal monitoring using MB-102 and dual fluorescent tracers. We conclude with a discussion on the development, validation, and clinical integration of these advancements, which may redefine renal function assessment in the years to come.

The dual sugar absorption test as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (molecular weight [MW] = 372) compares to lactulose (L) (MW = 342) and rhamnose (R) (MW = 164)-based dual sugar absorption test as a measure of gut permeability in people with a spectrum of permeability including those with Crohn's disease (CD).

We performed a single-center, randomized, open-label, crossover study comparing orally administered MB-102 (1.5 or 3.0 mg/kg) to L (1000 mg) and R (200 mg). Adults with active small bowel CD on magnetic resonance enterography (cases) and healthy adults (controls) were randomized to receive either MB-102 or L and R on study day 1, and the other tracer 3 to 7 days later. Urine was collected at baseline and 1, 2, 4, 6, 8, 10, and 12 hours after tracer ingestion to calculate the cumulative urinary percent excretion of MB-102 and L and R.

Nine cases and 10 controls completed the study without serious adverse events. Urinary recovery of administered MB-102 correlated with recovery of lactulose (r-squared = 0.83) for all participants. MB-102 urine recovery was also tracked with the L:R ratio urine recovery (r-squared = 0.57). In controls, the percentages of L and MB-102 recovered were similar within a narrow range, unlike in CD patients.

This first-in-human study of an orally administered fluorophore to quantify gastrointestinal permeability in adults with CD demonstrates that MB-102 is well tolerated, and its recovery in urine mirrors that of percent L and the L:R ratio.