title: Ten plus one challenges in diseases of the lysosomal system.
abstract: The advent of the first effective specific therapy for a lysosomal storage disease (LSDs), Gaucher disease type 1, by Roscoe O. Brady was foundational for development of additional treatments for this group of rare diseases. The past 26years, since the approval of enzyme therapy for Gaucher disease type 1, have witnessed a burgeoning understanding of LSDs at genetic, molecular, biochemical, cell biologic, and clinical levels. Simultaneously, this expansion of knowledge has exposed our incomplete understanding of the individual pathophysiologies of LSDs as well as difficult challenges for improvement in therapy and therapeutic outcomes for afflicted individuals. Here, 10 such challenges/problems representing major impediments, which need to be overcome, to move forward toward the goals of more effective and complete therapies for these devastating diseases.
authors.affiliation: Children's Hospital Medical Center, Cincinnati, OH, United States; Kiniksa Pharmaceuticals, Ltd., Wellesley, MA, United States. Electronic address: ggrabowski@kiniksa.com.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Grabowski
authors.affiliation: Department of Pediatrics, University of Minnesota, School of Medicine, Minneapolis, MN, United States; Department of Experimental and Clinical Pharmacology, University of Minnesota, School of Medicine, Minneapolis, MN, United States.
authors.forename: Chester
authors.initials: C
authors.lastname: Whitley
mesh_terms: D018450:Disease Progression; D056947:Enzyme Replacement Therapy / Q000379:methods*; D005776:Gaucher Disease / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D016896:Treatment Outcome