Advances in the treatment of neuronal ceroid lipofuscinosis

作者：Sondhi Dolan; Rosenberg Jonathan B; Van de Graaf Benjamin G; Kaminsky Stephen M; Crystal Ronald G^*

来源：Expert Opinion on Orphan Drugs, 2013, 1(12): 951-975.

DOI：10.1517/21678707.2013.852081

• adeno-associated virus
• ceroid lipofuscinosis neuronal
• clinical trials
• gene therapy
• neuronal ceroid lipofuscinoses
• palmitoyl protein thioesterase-1
• tripeptidyl peptidase-1

Introduction: Neuronal ceroid lipofuscinoses (NCL) represent a class of neurodegenerative disorders typically characterized by cognitive and visual impairment, seizures, deterioration of motor skills and early mortality. There has been increased interest in developing therapies directed towards slowing the progression, and possibly preventing and reversing the impact of these disorders. Despite many challenges, including the presence of the blood-brain barrier which prevents access to the central nervous system (CNS) and the need to markedly remove accumulated debris throughout the CNS, many treatment modalities have been proposed, including enzyme replacement therapy, gene therapy, stem cell therapy, small molecule pharmacotherapy and diet modifications. Some therapies have demonstrated measures of success, and these have progressed to human clinical trials. Continued development of current therapies and discovery of newer approaches will be essential for success.
Areas covered: The reader will be introduced to the 14 known NCLs, the current approach to therapies, the evidence for efficacy and the challenges to success both at the pre-clinical and clinical stage. This review corresponds to the literatures covering the years from 1968 to mid-2013.
Expert opinion: Much progress has been made in the classification of this family of neurologic diseases, including the genetic basis and functional outcomes which have led to the evaluation of several therapeutic interventions. These include enzyme replacement therapy, gene therapy, stem cell therapy, small molecule pharmacotherapy and diet modifications, each of which has associated pros and cons. Successful therapies in the future may necessitate the combination of two or more therapeutic modalities.

• 出版日期2013-12