Genetics and biological therapies for Alport syndrome

Introduction: Alport syndrome is a genetic disorder of basement membranes caused by mutations in the type IV collagen genes COL4A3, COL4A4 and COL4A5. The Alport phenotype includes progressive hematuric nephropathy often leading to end-stage renal disease (ESRD), sensorineural deafness and ocular lesions. Results of laboratory and clinical research studies form the basis for current treatment recommendations aimed at delaying ESRD and indicate novel therapeutic approaches that may prevent ESRD altogether in many affected individuals. Areas covered: This review of Alport syndrome therapeutics begins with a summary of current understanding of pathogenetic mechanisms, followed by discussion of intervention targeting tubular injury and interstitial fibrosis, cell-based therapies, modulation of glomerular signaling and gene delivery and manipulation. A PubMed search using the term 'Alport syndrome' was used to gather literature for this monograph. Expert opinion: Experimental and clinical data support the early initiation of ACE inhibition to delay the onset of ESRD. Novel therapies targeting disease pathways activated by type IV collagen deficiency in basement membranes have the potential to further improve outcomes, especially in patients with genotypes associated with relatively rapid loss of renal function.