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Gene therapy for glycogen storage diseases
Dwight D Koeberl1,2, Rebecca L Koch1, Jeong-A Lim1
1Division of Medical Genetics, Department of Pediatrics, Duke University Medical School, Durham, North Carolina, USA.
Journal of Inherited Metabolic Disease
|July 8, 2023
Summary
Gene therapy offers a promising new treatment for glycogen storage disorders (GSDs), rare inherited metabolic diseases. Clinical trials are underway for Pompe disease and GSD Ia, addressing an unmet need for stable therapies.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Glycogen storage disorders (GSDs) are inherited metabolic diseases caused by enzyme deficiencies in glycogen metabolism.
- GSDs lead to glycogen accumulation and impaired glucose production, causing diverse symptoms affecting organs like the liver, kidneys, and muscles.
- Specific GSDs, such as GSD Ia and Pompe disease, present unique clinical challenges including hypoglycemia, organ damage, and cardiorespiratory failure.
Purpose of the Study:
- To review the development and current status of gene therapy for GSDs.
- To highlight the use of animal models in evaluating novel gene therapies and genome editing techniques.
- To discuss the progress of gene therapy clinical trials and their challenges.
Main Methods:
- Literature review of gene therapy development for GSDs.
- Analysis of animal models used to test gene therapy and genome editing.
- Examination of clinical trial data for GSDs, focusing on Pompe disease and GSD Ia.
Main Results:
- Gene therapy for Pompe disease and GSD Ia has advanced to Phase I and Phase III clinical trials, respectively.
- Adeno-associated virus vectors are being evaluated for safety and bioactivity in these trials.
- Clinical research provides essential outcome measures for evaluating therapeutic benefits.
Conclusions:
- Gene therapy and genome editing show promise for treating GSDs, addressing a significant unmet medical need.
- Challenges remain in clinical implementation, including managing immune responses and toxicities observed in ongoing trials.
- Continued research into GSD natural history and therapeutic development is crucial for improving patient outcomes.
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