Treatments for lysosomal storage disorders

2010 ◽  
Vol 38 (6) ◽  
pp. 1465-1468 ◽  
Author(s):  
Robin Lachmann
Keyword(s):  
Genetic Disorders ◽  
Lysosomal Storage Disorders ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Haemopoietic Stem Cell ◽  
Substrate Reduction ◽  
Haemopoietic Stem Cell Transplantation ◽  
Late Stages ◽  
Storage Disorders

There are over 70 human diseases that are caused by defects in various aspects of lysosomal function. Until 20 years ago, the only specific therapy available for lysosomal storage disorders was allogeneic haemopoietic stem cell transplantation. Over the last two decades, there has been remarkable progress and there are now licensed treatments for seven of these diseases. In some cases, a choice of agents is available. For selected enzyme-deficiency disordes, ERT (enzyme-replacement therapy) has proved to be highly effective. In other cases, ERT has been less impressive, and it seems that it is not possible to efficiently deliver recombinant enzyme to all tissues. These difficulties have led to the development of other small-molecule-based therapies, and a drug for SRT (substrate-reduction therapy) is now licensed and potential chaperone molecules for ERT are in the late stages of clinical development. Nonetheless, there is still significant unmet clinical need, particularly when it comes to treating LSDs which affect the brain. LSDs have led the way in the development of treatment for genetic disorders, and it seems likely that there will be further therapeutic innovations in the future.

Treatment for Lysosomal Storage Disorders

2020 ◽  
Vol 26 (40) ◽  
pp. 5110-5118
Author(s):  
Jayesh Sheth ◽  
Aadhira Nair
Keyword(s):  
Transmembrane Protein ◽  
Treatment Strategies ◽  
Lysosomal Storage Disorders ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Substrate Reduction ◽  
Organ Systems ◽  
Disease Condition ◽  
Storage Disorders

: Lysosomal storage disorders comprise a group of approximately 70 types of inherited diseases resulting due to lysosomal gene defects. The outcome of the defect is a deficiency in either of the three: namely, lysosomal enzymes, activator protein, or transmembrane protein, as a result of which there is an unwanted accumulation of biomolecules inside the lysosomes. The pathophysiology of these conditions is complex affecting several organ systems and nervous system involvement in a majority of cases. Several research studies have well elucidated the mechanism underlying the disease condition leading to the development in devising the treatment strategies for the same. Currently, these approaches aim to reduce the severity of symptoms or delay the disease progression but do not provide a complete cure. The main treatment methods include Enzyme replacement therapy, Bone marrow transplantation, Substrate reduction therapy, use of molecular chaperones, and Gene therapy. This review article presents an elaborate description of these strategies and discusses the ongoing studies for the same.

scholarly journals Small–molecule therapeutics for the treatment of glycolipid lysosomal storage disorders

2003 ◽  
Vol 358 (1433) ◽  
pp. 927-945 ◽  
Author(s):  
Terry D. Butters ◽  
Howard R. Mellor ◽  
Keishi Narita ◽  
Raymond A. Dwek ◽  
Frances M. Platt
Keyword(s):  
Catalytic Activity ◽  
Lysosomal Storage Disorders ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
Substrate Reduction ◽  
Treatment Demand ◽  
Small Molecule Therapeutics ◽  
Storage Disorders

Glycosphingolipid (GSL) lysosomal storage disorders are a small but challenging group of human diseases to treat. Although these disorders appear to be monogenic in origin, where the catalytic activity of enzymes in GSL catabolism is impaired, the clinical presentation and severity of disease are heterogeneous. Present attitudes to treatment demand individual therapeutics designed to match the specific disease–related gene defect; this is an acceptable approach for those diseases with high frequency, but it lacks viability for extremely rare conditions. An alternative therapeutic approach termed ‘substrate deprivation’ or ‘substrate reduction therapy’ (SRT) aims to balance cellular GSL biosynthesis with the impairment in catalytic activity seen in lysosomal storage disorders. The development of N–alkylated iminosugars that have inhibitory activity against the first enzyme in the pathway for glucosylating sphingolipid in eukaryotic cells, ceramide–specific glucosyltransferase, offers a generic therapeutic for the treatment of all glucosphingolipidoses. The successful use of N–alkylated iminosugars to establish SRT as an alternative therapeutic strategy has been demonstrated in in vitro , in vivo and in clinical trials for type 1 Gaucher disease. The implications of these studies and the prospects of improvement to the design of iminosugar compounds for treating Gaucher and other GSL lysosomal storage disorders will be discussed.

scholarly journals Genetic Substrate Reduction Therapy: A Promising Approach for Lysosomal Storage Disorders

Diseases ◽  
2016 ◽  
Vol 4 (4) ◽  
pp. 33 ◽  
Author(s):  
Maria Coutinho ◽  
Juliana Santos ◽  
Liliana Matos ◽  
Sandra Alves
Keyword(s):  
Lysosomal Storage Disorders ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
Substrate Reduction ◽  
Storage Disorders

Lysosomal Storage Disorders

2017 ◽  
Author(s):  
Gustavo H. B. Maegawa
Keyword(s):  
Molecular Mechanisms ◽  
Substantial Improvement ◽  
Lysosomal Storage Disorders ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Psychiatric Disturbances ◽  
Extrapyramidal Signs ◽  
Storage Disorders

The lysosomal storage disorders (LSDs) are a group of inborn organelle disorders, clinically heterogeneous, and biochemically characterized by accumulation of nondegraded macromolecules primarily in the lysosomal and other cellular compartments. Given the common and essential cellular function of the lysosomal system in different organs and systems, patients afflicted with these disorders present a broad range of clinical problems, including neurological problems, visceromegaly, and skeletal deformities. Onset of symptoms may range from fetal period to adulthood. The neurological problems include developmental delay, seizures, acroparesthesia, motor weakness, muscle wasting, behavioral/psychiatric disturbances, cerebrovascular ischemic events, and extrapyramidal signs. Patients may present with symptoms later that include psychiatric manifestations, are slowly progressive, and may precede other neurologic or systemic features. Most of LSDs are autosomal recessive; however, a few are X-linked with symptpmatic female carriers (e.g., Fabry disease). In most of them, the diagnosis is established by biochemical and/or molecular assays. In terms of management, disease-modifying therapies include enzyme replacement, hematopoietic stem cell transplantation, and substrate reduction therapy. Patients and their families require genetic counseling regarding reproductive risks, disease prognosis, and therapeutic options. Investigations of disease molecular mechanisms provide insights into potential targets for the development of therapeutic strategies. Supportive care has been the key and essential for most LSDs, resulting in substantial improvement in quality of life of patients and families.

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