1. Novel therapeutic approaches to xeroderma pigmentosum.
- Author
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Weon JL and Glass DA 2nd
- Subjects
- Acetohexamide pharmacology, Acetohexamide therapeutic use, Administration, Cutaneous, Animals, Caloric Restriction, DNA Damage radiation effects, Dermatology methods, Dermatology trends, Disease Models, Animal, Humans, Niacinamide pharmacology, Niacinamide therapeutic use, Protective Clothing, Randomized Controlled Trials as Topic, Sulfonylurea Compounds pharmacology, Sunlight adverse effects, Treatment Outcome, Ultraviolet Rays adverse effects, Xeroderma Pigmentosum genetics, DNA Damage drug effects, DNA Repair drug effects, Sulfonylurea Compounds therapeutic use, Sunscreening Agents administration & dosage, Xeroderma Pigmentosum therapy
- Abstract
Background: The study of xeroderma pigmentosum has yielded unforeseen advances regarding how defects in the nucleotide excision repair pathway result in this devastating disease, but development of therapeutic strategies has trailed behind the mechanistic discoveries., Objectives: This review aims to cover clinical presentation, molecular mechanisms and current management, and highlights more recent insights into targeting the deficiencies secondary to the DNA repair defects to prevent skin cancer and/or neurological degeneration., Methods: This review article discusses novel therapeutic approaches to xeroderma pigmentosum that focus on metabolic defects downstream of nucleotide excision repair., Results: Current research demonstrates that specific sulfonylureas promote clearance of DNA damage and increase resistance to ultraviolet radiation in a cellular model of xeroderma pigmentosum. Moreover, nicotinamide attenuates the effects of ultraviolet radiation in cells, and caloric restriction decreases DNA damage burden in animal models of xeroderma pigmentosum., Conclusions: Clinical management of patients with xeroderma pigmentosum still focuses on preventative avoidance of sun exposure as opposed to therapies that would improve the patients' condition; thus, novel approaches to this disease are warranted., (© 2018 British Association of Dermatologists.)
- Published
- 2019
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