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Current and Future Treatments for Lysosomal Storage Disorders

  • Pediatric Neurology (R-M Boustany, Section Editor)
  • Published:
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Abstract

Purpose of review Lysosomal storage disorders (LSDs) are a class of genetic disorders that are a testing ground for the invention of novel therapeutics including enzyme replacement therapy (ERT), substrate reduction therapy (SRT), gene therapy, and hematopoietic stem cell transplant (HSCT). This review summarizes recently approved drugs, then examines the successful clinical trials in gene therapy and HSCT.

Recent findings The FDA has recently approved a second SRT by reversing an earlier FDA decision, suggesting a favorable regulatory landscape going forward. Adeno-associated virus therapies, adenovirus therapies, and HSCT have overcome limitations of earlier clinical and preclinical trials, suggesting that gene therapy may be a reality for LSDs in the near future. At the same time, the first EU-approved gene therapy drug, Glybera, has been discontinued, and other ex vivo-based therapies although approved for clinical use have failed to be widely adapted and are no longer economically viable.

Summary There are now 11 ERTs and two SRTs approved for LSDs in the USA. Gene therapy approaches and HSCT have also demonstrated promising clinical trial results suggesting that these therapies are on the frontier. Challenges that remain include navigating immune responses, developing drugs capable of crossing the blood-brain barrier (BBB), developing therapies that can reverse end-organ damage, and achieving these goals in a safe, ethical, and financially sustainable manner. The amount of active development and a track record of iterative progress suggest that treatments for LSDs will continue to be a field of innovation, problem solving, and success.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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  1. Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, 48824, USA

    David P. W. Rastall PhD & Andrea Amalfitano DO, PhD

  2. Department of Pediatrics, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, 48824, USA

    Andrea Amalfitano DO, PhD

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David P. W. Rastall declares no potential conflicts of interest.

Andrea Amalfitano reports grants from Muscular Dystrophy Association of USA, Acid Maltase Deficiency Association of America, Genzyme Corporation, and Venn Therapeutics. Dr. Amalfitano reports personal fees from Genzyme Corporation, Venn Therapeutics, and Etubics Corp and reports an issued patent (US #7666405).

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Rastall, D.P.W., Amalfitano, A. Current and Future Treatments for Lysosomal Storage Disorders. Curr Treat Options Neurol 19, 45 (2017). https://doi.org/10.1007/s11940-017-0481-2

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