An update on gene therapy for lysosomal storage disorders. Expert Opin Biol Ther 2019 Jul;19(7):655-670
Date
05/07/2019Pubmed ID
31056978DOI
10.1080/14712598.2019.1607837Scopus ID
2-s2.0-85068638885 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
INTRODUCTION: Gene therapies can be envisioned for many disorders where conventional therapies fall short. Lysosomal Storage Disorders (LSDs) are inherited, mostly monogenic, disorders resulting from deficient lysosomal enzyme or co-factor activity. Existing standard-of-care treatments for LSDs are expensive and can negatively impact quality-of-life. They also may not be sufficiently efficacious. LSDs are particularly amenable to gene therapy as modified cells can secrete functional enzyme that can also correct unmodified cells. Gene therapies may thus be able to provide sustained long-term correction for LSD patients.
AREAS COVERED: We highlight recent advances and discuss advantages/disadvantages of gene therapies with a focus on lentiviral and adeno-associated virus vectors currently in clinical trials for LSDs. We also mention promising strategies that are close to clinical testing. We emphasize protocols using ex vivo hematopoietic stem cell-directed gene therapy, systemic/liver-directed gene therapy, and brain-directed gene therapy. We also discuss next-generation gene therapy approaches and how they may address emerging challenges in the field.
EXPERT OPINION: Gene therapy is still in its infancy with respect to LSDs. However, efficacy and safety has been demonstrated in numerous pre-clinical studies, and promising clinical results suggest that gene therapy treatment for several LSDs is a real possibility.
Author List
Nagree MS, Scalia S, McKillop WM, Medin JAAuthor
Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBrain
Cell- and Tissue-Based Therapy
Dependovirus
Genetic Therapy
Genetic Vectors
Hematopoietic Stem Cells
Humans
Liver
Lysosomal Storage Diseases
