DOCUMENT

24 | InTouch SUMMER 2024 POMPE DISEASE (ACID MALTASE DEFICIENCY) Current and Potential Therapies for Pompe Disease 1. Enzyme Replacement Therapy (ERT): a. What It Is: ERT involves infusing a synthetic version of the missing enzyme, acid alpha-glucosidase, into the body to help break down glycogen in the lysosomes. b. Current Options: The first ERT drug, alglucosidase alfa, was initially approved in the US in 2006. It helps manage symptoms, particularly in infants with severe forms of the disease, by improving heart function and muscle strength. c. New Developments: Newer versions of ERT, like avalglucosidase alfa, are being developed to improve how effectively the enzyme reaches and is used by the muscles. 2. Gene Therapy: a. What It Is: Gene therapy aims to provide a long-term solution by delivering a healthy copy of the GAA gene directly into the patient’s cells, potentially allowing their own body to produce the needed enzyme. b. Current Research: Scientists are exploring the use of viral vectors (harmless viruses) to carry the healthy gene into cells. Trials are ongoing to test the safety and effectiveness of this approach. 3. Pharmacological Chaperones: a. What They Are: These are small molecules that help stabilize the enzyme so it can function better and last longer in the body. b. Potential Benefits: By improving the stability of the enzyme, these chaperones could enhance the effects of ERT, making it more effective. 4. Substrate Reduction Therapy: a. What It Is: This approach aims to reduce the production of glycogen, the substance that builds up in the cells, thereby decreasing the burden on the lysosomes. b. Research Status: This is still largely in the experimental stage, with scientists investigating how best to lower glycogen levels safely. Main Themes of Ongoing Research 1. Improving Enzyme Delivery: Researchers are working to enhance how well ERT drugs are delivered to and taken up by muscle tissue. This includes modifying the enzyme itself to improve its targeting and uptake by cells. 2. Understanding Disease Mechanisms: Scientists are studying the underlying biology of Pompe disease to understand why muscle damage occurs and how it progresses. This knowledge helps identify new targets for therapy and improve existing treatments. 3. Exploring Combination Therapies: Combining different treatment approaches, such as ERT with chaperones or gene therapy, might offer better outcomes than any single therapy alone. Research is ongoing to find the best combinations. 4. Newborn Screening and Early Intervention: Early detection of infantile onset Pompe disease is crucial for starting treatment before symptoms become severe. Research continues to refine screening methods and develop guidelines for early intervention. 5. Addressing Immune Responses: Some patients develop immune reactions to ERT, which can reduce its effectiveness. Researchers are exploring ways to manage or prevent these immune responses, including using immune tolerance therapies. These ongoing efforts in research and therapy development aim to improve the quality of life and long-term outcomes for individuals with Pompe disease. As with many rare diseases, there is an increasing emphasis on patient advocacy and support networks, which are invaluable in providing resources and information for affected families and in promoting research. As scientific advancements continue, there is a growing hope for more effective treatments and possibly even a cure. RESOURCES AND REFERENCES: The National Metabolic Service, New Zealand Pompe.Community Acid Maltase Deficiency Association (AMDA) International Pompe Association (IPA) Kohler L, Puertollano R, Raben N. Pompe Disease: From Basic Science to Therapy. Neurotherapeutics. 2018;15(4):928-942. doi:10.1007/s13311-018-0655-y. Meena NK, Raben N. Pompe Disease: New Developments in an Old Lysosomal Storage Disorder. Biomolecules. 2020; 10(9):1339. https://doi.org/10.3390/ biom10091339 Hahn S. Lysosomal acid alpha-glucosidase deficiency (Pompe disease, glycogen storage disease II, acid maltase deficiency). In: UpToDate, Connor RF (Ed), Wolters Kluwer. (Accessed on 14 October 2024.)