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Alport Syndrome


About Alport Syndrome

Alport syndrome is an inherited form of kidney disease caused by mutations in the type IV collagen genes (Col4A3, Col4A4 and Col4A5). The prevalence of mutations in the collagen IV family of genes is estimated to be 1 in 5,000 individuals (Pirson, 1999). Type IV collagen is important for maintaining the integrity of the glomerular basement membrane (GBM), a vital component in the kidney structure and filtration process. The genetic mutation in the collagen gene results in thickening in the GBM and impairment of glomerulus filtration.

Alport syndrome patients experience a progressive loss of kidney function, which ultimately leads to end stage renal disease requiring dialysis or kidney transplantation often by early adulthood, or even death (Cosgrove, 2012; Jais et al., 2000; Oka et al., 2014). Patients with Alport syndrome are thought to account for approximately 2.5% of all renal transplants in the US. Alport syndrome can also cause hearing loss and eye abnormalities during late childhood or early adolescence because the collagen IV isotypes are also expressed in the inner ear and eye. The major clinical concern, however, is the loss of renal function. With no approved therapies, Alport syndrome is a disease with urgent unmet medical needs.

About RG-012

RG-012 is being developed by Regulus in a strategic alliance with Genzyme, a Sanofi company, for the treatment of Alport syndrome. RG-012 is a single stranded, chemically modified oligonucleotide that binds to and inhibits the function of miR-21 for the treatment of Alport syndrome.

In preclinical studies, RG-012 has demonstrated potent inhibition of miR-21 in vitro and in vivo, and in an experimental model of Alport syndrome demonstrated a decrease in the rate of progression of renal fibrosis, an increase in the lifespan of the mice by up to fifty percent, and an additive benefit in combination with an emerging standard of care therapy.  Further, RG-012 has received orphan drug status from the U.S. Food and Drug Administration and European Commission as a therapeutic in development for the treatment of Alport syndrome.