Emerging treatments and personalised medicine for ciliopathies associated with cystic kidney disease

Introduction: Renal ciliopathies are a class of heterogeneous disorders that can manifest with nephronophthisis, cystic kidneys or renal cystic dysplasia. Disease causing genes encode for ciliary proteins, suggesting that defects in the primary cilium underlie a common pathogenesis. Currently, no cure and limited treatment options are available for renal ciliopathies patients. Areas covered: We will review here the results of preclinical and clinical studies on drugs that modify dysregulated pathways in ciliopathies associated with cystic kidney disease. Substantial progress in the clarification of underpinning molecular mechanisms along with implementation of in vivo models has led to the identification of several compounds with promising therapeutic effects in preclinical studies. Clinical trials are currently evaluating safety and efficacy of several emerging therapies in human, but to date only the V2 receptor antagonist tolvaptan has been utilised in the clinic for the treatment of adult patients with rapidly progressive polycystic kidney. Expert opinion: The extreme genetic and clinical heterogeneity that characterizes renal ciliopathies patients may in part explain the limited success of clinical trials and highlights the need for precision treatments. Gene based therapies and personalized drug screenings may represent the future standard of care for renal ciliopathies patients with cystic kidney disease.