Gene therapy for neurologic manifestations of mucopolysaccharidoses

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

Introduction: Mucopolysaccharidoses (MPS) are a family of lysosomal disorders caused by mutations in genes that encode enzymes involved in the catabolism of glycoaminoglycans. These mutations affect multiple organ systems and can be particularly deleterious to the nervous system. At the present time, enzyme replacement therapy and hematopoietic stem-cell therapy are used to treat patients with different forms of these disorders. However, to a great extent, the nervous system is not adequately responsive to current therapeutic approaches. Areas covered: Recent advances in gene therapy show great promise for treating MPS. This article reviews the current state of the art for routes of delivery in developing genetic therapies for treating the neurologic manifestations of MPS. Expert opinion: Gene therapy for treating neurological manifestations of MPS can be achieved by intraventricular, intrathecal, intranasal and systemic administrations. The intraventricular route of administration appears to provide the most widespread distribution of gene therapy vectors to the brain. The intrathecal route of delivery results in predominant distribution to the caudal areas of the brain. The systemic route of delivery via intravenous infusion can also achieve widespread delivery to the CNS; however, the distribution to the brain is greatly dependent on the vector system. Intravenous delivery using lentiviral vectors appear to be less effective than adeno-associated viral (AAV) vectors. Moreover, some subtypes of AAV vectors are more effective than others in crossing the blood-brain barrier. In summary, the recent advances in gene vector technology and routes of delivery to the CNS will facilitate the clinical translation of gene therapy for the treatment of the neurological manifestations of MPS.

Original languageEnglish (US)
Pages (from-to)283-296
Number of pages14
JournalExpert Opinion on Drug Delivery
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2015

Fingerprint

Mucopolysaccharidoses
Neurologic Manifestations
Genetic Therapy
Nervous System
Brain
Enzyme Replacement Therapy
Intranasal Administration
Mutation
Expert Testimony
Cell- and Tissue-Based Therapy
Hematopoietic Stem Cells
Blood-Brain Barrier
Intravenous Infusions
Genes
Technology
Enzymes
Therapeutics

Keywords

  • Enzyme replacement therapy
  • Gene therapy
  • Hunter syndrome
  • Hurler syndrome
  • Sanfilippo syndrome

Cite this

Gene therapy for neurologic manifestations of mucopolysaccharidoses. / Wolf, Daniel A.; Banerjee, Sharbani; Hackett, Perry B.; Whitley, Chester B.; McIvor, R. Scott; Low, Walter C.

In: Expert Opinion on Drug Delivery, Vol. 12, No. 2, 01.02.2015, p. 283-296.

Research output: Contribution to journalReview article

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