Can Alport syndrome be treated by gene therapy?

Alport syndrome, also termed hereditary nephritis, was initially described in 1927 by A.C. Alport [1] as an inherited kidney disease characterized by hematuria and sensorineural deafness. Later, ocular lesions were also associated with the syndrome and, with the introduction of the electron microscope, irregularities and disruptions in the glomerular basement membrane (GBM) were shown to be typical for this disorder as well [2, 31. The disease is highly progressive and usually leads to renal failure during adolescence or before middle age. The disease is primarily inherited as an X-chromosome linked dominant trait with an estimated gene frequency of 1:5,000 to 1:10,000, but autosomal forms also exist [2, 3]. The defective gene in X-linked Alport syndrome was located in 1988 and 1989 to the long arm of the X chromosome [4—61. In 1990, a gene encoding a novel basement membrane (type IV) collagen a5 chain was discovered and localized to the Alport gene region on chromosome X, and this was soon followed by identification of mutations in this gene in Alport patients [7, 8]. More recently, mutations have also been reported in the genes for the a3 and a4 type IV collagen chains in the rarer autosomal forms of Alport syndrome