BMN-185: IgA Protease for IgA Nephropathy
IgA nephropathy is a renal-limited form of glomerulonephritis characterized by deposition of IgA containing immune deposits in the glomerular mesangium. The glomerular deposits of IgA nephropathy appear to be exclusively of the IgA1 subclass. The reported incidence in the US is between 5 and 12 cases per million per year, and the US reported prevalence is 60,000-80,000. Patients may present with episodes of macroscopic hematuria (tea-colored urine) that may coincide with an infection of the upper respiratory tract, or proteinuria in patients without symptoms. Diagnosis is by identification of mesangial IgA deposits by renal biopsy. IgA nephropathy has a variable course ranging from benign to rapidly progressive renal failure. Between 15 and 40 percent of patients will eventually develop end stage renal disease (ESRD). Slowly progressive renal failure develops in most of these patients.
BioMarin’s proposed treatment for IgA nephropathy is the use of IgA proteases, naturally produced by bacteria, which specifically cleave human IgA1. After treatment by systemic injection of the IgA1 protease, the cleaved IgA fragments would be cleared from the kidney, potentially causing a reversal of the condition. At this stage, the project involves proof-of-principle and efficacy testing in preclinical models, and is being done in collaboration with IGAN Biosciences (Boston, MA).
