Orly Tabachnikov, Karl Skorecki, Etty Kruzel-Davila
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引用次数: 0
Abstract
Purpose of review: More than a decade ago, apolipoprotein L1 ( APOL1 ) risk alleles designated G1 and G2, were discovered to be causally associated with markedly increased risk for progressive kidney disease in individuals of recent African ancestry. Gratifying progress has been made during the intervening years, extending to the development and clinical testing of genomically precise small molecule therapy accompanied by emergence of RNA medicine platforms and clinical testing within just over a decade.
Recent findings: Given the plethora of excellent prior review articles, we will focus on new findings regarding unresolved questions relating mechanism of cell injury with mode of inheritance, regulation and modulation of APOL1 activity, modifiers and triggers for APOL1 kidney risk penetrance, the pleiotropic spectrum of APOL1 related disease beyond the kidney - all within the context of relevance to therapeutic advances.
Summary: Notwithstanding remaining controversies and uncertainties, promising genomically precise therapies targeted at APOL1 mRNA using antisense oligonucleotides (ASO), inhibitors of APOL1 expression, and small molecules that specifically bind and inhibit APOL1 cation flux are emerging, many already at the clinical trial stage. These therapies hold great promise for mitigating APOL1 kidney injury and possibly other systemic phenotypes as well. A challenge will be to develop guidelines for appropriate use in susceptible individuals who will derive the greatest benefit.
期刊介绍:
A reader-friendly resource, Current Opinion in Nephrology and Hypertension provides an up-to-date account of the most important advances in the field of nephrology and hypertension. Each issue contains either two or three sections delivering a diverse and comprehensive coverage of all the key issues, including pathophysiology of hypertension, circulation and hemodynamics, and clinical nephrology. Current Opinion in Nephrology and Hypertension is an indispensable journal for the busy clinician, researcher or student.