New therapeutic options for Alport syndrome

Abstract

Alport syndrome (AS) is the most frequent inherited kidney disease after autosomal dominant polycystic kidney disease. It has three different patterns of inheritance—autosomal dominant, autosomal recessive and X-linked—which in part explains the wide spectrum of disease, ranging from isolated microhaematuria to end-stage renal disease early in life. The search for a treatment for AS is being pursued vigorously, not only because of the obvious unmet need but also because AS is a rare disease and any drug approved will have an orphan drug designation with its various benefits. Moreover, AS patients are quite young with very few comorbidities, which facilitates clinical trials. This review identifies the particularities of each pattern of inheritance but focuses mainly on new drugs or therapeutic targets for the disease. Most treatment-related investigations are directed not at the main abnormality in AS, namely collagen IV composition, but rather at the associated inflammation and fibrosis. Thus, AS may serve as a proof of concept for numerous drugs of potential value in many diseases that cause chronic kidney disease.

A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport’s syndrome

“…6,18 The unique study objectives are to determine the safety and efficacy of ramipril therapy in children, before they develop kidney damage. 13,22 The EARLY PRO-TECT Alport trial still is one of very few double-blind placebo-controlled randomized trials in children worldwide. It is the first prospective interventional clinical trial ever in AS.…”

An overview of the multi-pronged approach in the diagnosis of Alport syndrome for 22 children in Northeast China

“…In addition, future therapies, including stem cells, chaperon therapy, collagen receptor blockade and anti-microRNA therapy, will shed more lights on the protection of kidneys in AS patients from further damage [ 33 ]. Through different mechanisms, therapies such as Bardoxolone, anti-miRNA-21, paricalcitol, lipid-lowering agents and epidermal growth factor receptor inhibitor, may play a certain role in mitigating renal fibrosis [ 34 ]. Meanwhile, chaperone and stem-cell based therapies are expected to show therapeutic efficacy at the collagen chains and GBM level, respectively.…”

A review of multi-dimensional diagnosis of Alport syndrome in 22 children in Northeast China

“…[31] Through different mechanism, therapies such as Bardoxolone, anti-miRNA-21, paricalcitol, lipid-lowering agents and epidermal growth factor receptor inhibition play role in decreasing renal fibrosis. [32] Meanwhile, Chaperone and Stem-cell based therapies are expected to be therapeutic at collagen chains and GBM level respectively. However, when kidney failure is inevitable, patients with Alport syndrome who undergo renal transplantation would have generally excellent outcomes.…”