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. 2022 Sep;22(9):1117-1135.
doi: 10.1080/14712598.2022.2067476. Epub 2022 Apr 27.

What's new and what's next for gene therapy in Pompe disease?

Angela L Roger  1 , Ronit Sethi  1 , Meredith L Huston  1 , Evelyn Scarrow  1 , Joy Bao-Dai  1 , Elias Lai  1 , Debolina D Biswas  1 , Léa El Haddad  1 , Laura M Strickland  1 , Priya S Kishnani  2 , Mai K ElMallah  1
Affiliations

What's new and what's next for gene therapy in Pompe disease?

Angela L Roger et al. Expert Opin Biol Ther. 2022 Sep.

Abstract

Introduction: Pompe disease is an autosomal recessive disorder caused by a deficiency of acid-α-glucosidase (GAA), an enzyme responsible for hydrolyzing lysosomal glycogen. A lack of GAA leads to accumulation of glycogen in the lysosomes of cardiac, skeletal, and smooth muscle cells, as well as in the central and peripheral nervous system. Enzyme replacement therapy has been the standard of care for 15 years and slows disease progression, particularly in the heart, and improves survival. However, there are limitations of ERT success, which gene therapy can overcome.

Areas covered: Gene therapy offers several advantages including prolonged and consistent GAA expression and correction of skeletal muscle as well as the critical CNS pathology. We provide a systematic review of the preclinical and clinical outcomes of adeno-associated viral mediated gene therapy and alternative gene therapy strategies, highlighting what has been successful.

Expert opinion: Although the preclinical and clinical studies so far have been promising, barriers exist that need to be addressed in gene therapy for Pompe disease. New strategies including novel capsids for better targeting, optimized DNA vectors, and adjuctive therapies will allow for a lower dose, and ameliorate the immune response.

Keywords: AAV; GAA; Pompe disease; acid alpha-glucosidase; gene therapy; neuromuscular disorder.

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Conflict of interest statement

Declaration of interest

AL Roger has disclosed Pfizer-NCBiotech Distinguished Postdoctoral Fellowship in Gene Therapy and funding 1K99HL161420–01. MK ElMallah has disclosed funding NICHD R01 HD099486 and received research support from Sarepta Therapeutics. PS Kishnani and Duke University have equity in Asklepios Biopharmaceutical, Inc. (AskBio), which is developing gene therapy for Pompe disease. PS Kishnani has received research/grant support from Sanofi Genzyme, Valerion Therapeutics and Amicus Therapeutics; has received consulting fees and honoraria from Sanofi Genzyme, Amicus Therapeutics, Vertex Pharmaceuticals and AskBio; and is a member of the Pompe and Gaucher Disease Registry Advisory Board for Sanofi Genzyme, Amicus Therapeutics and Baebies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1:
Figure 1:. Inclusion and exclusion of manuscripts that contribute to this review.
See this image and copyright information in PMC

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