• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.17-18
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• 2016

Enzyme replacement therapy (ERT) is a well-established means of treating lysosomal storage disease (LSD). However, classical IV infusion based ERT method produces less than ideal results, especially, CNS defects and quality of life in patients. To improve these main problems of parental IV formulation for LSDs, we investigate modified ERT method and evaluated the efficacy in animal model.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.18-22
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• 2005

Pompe disease is a genetic disorder caused by a deficiency of acid ${\alpha}$-glucosidase (GAA). This enzyme defect results in lysosomal glycogen accumulation in multiple tissues and cell types, with cardiac, skeletal, and smooth muscle cells the most seriously affected. Infantile-onset Pompe disease is uniformly lethal. Affected infants present in the first few months of life with hypotonia, generalized muscle weakness, and a hypertrophic cardiomyopathy, followed by death from cardiorespiratory failure or respiratory infection, usually by 1 year of age. Late-onset forms is characterized by a lack of severe cardiac involvement and a less severe short-term prognosis. Enzyme replacement therapy for Pompe disease is intended to address directly the underlying metabolic defect via intravenous infusions of recombinant human GAA to provide the missing enzyme. We experienced one case of Pompe disease in 3-years old boy that has improved his exercise ability and cardiac function after GAA enzyme replacement therapy.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.1
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• pp.42-47
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• 2014

Gaucher disease is a multisystemic disorder arising from a deficient activity of the lysosomal enzyme glucocerebrosidase, which leads to accumulation of glycosylceraide and other glycolipids in the regiculoendothelial system. The characteristics of Gaucher disease are anemia, thrombocytopenia, hepatosplenomegaly, and skeletal disease. Enzyme replacement therapy (ERT) has been proven to prevent progressive manifestations of Gaucher disease and effective in improving anemia, thrombocytopenia, bone markers and biomarkers. However, some patient needs still remain unmet because of the inaccessibility of certain sites including brain, bone and various organs. ERT could not Improve the irreversible lesion such as liver fibrosis, hepatopulmonary syndrome, and necrosis or infarction of bone and other organs. Adult patients with Gaucher disease should be screened for longterm complication such as bone disease, pulmonary hypertension, gallstone, and cancer, especially in patients with splenectomy. Parkinsonism and polyneuropathy was also reported among patients with type 1 Gaucher disease, but ERT does not improve neurological function. We need to review the benefits and unmet needs of ERT in Gaucher disease.

• Journal of Genetic Medicine
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• v.20 no.1
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• pp.6-14
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• 2023

Fabry disease (FD), a rare X-linked lysosomal storage disorder, is caused by mutations in the α-galactosidase A gene gene encoding α-galactosidase A (α-Gal A). The functional deficiency of α-Gal A results in progressive accumulation of neutral glycosphingolipids, causing multi-organ damages including cardiac, renal, cerebrovascular systems. The current treatment is comprised of enzyme replacement therapy (ERT), oral pharmacological chaperone therapy and adjunctive supportive therapy. ERT has been introduced 20 years ago, changing the outcome of FD patients with proven effectiveness. However, FD patients have many unmet needs. ERT needs a life-long intravenous therapy, inefficient bio-distribution, and generation of anti-drug antibodies. Migalastat, a pharmacological chaperone, augmenting α-Gal A enzyme activity only in patients with mutations amenable to the therapy, is now available for clinical practice. Furthermore, these therapies should be initiated before the organ damage becomes irreversible. Development of novel drugs aim at improving the clinical effectiveness and convenience of therapy. Clinical trial of next generation ERT is underway. Polyethylene glycolylated enzyme has a longer half-life and potentially reduced antigenicity, compared with standard preparations with longer dosing interval. Moss-derived enzyme has a higher affinity for mannose receptors, and seems to have more efficient access to podocytes of kidney which is relatively resistant to reach by conventional ERT. Substrate reduction therapy is currently under clinical trial. Gene therapy has now been started in several clinical trials using in vivo and ex vivo technologies. Early results are emerging. Other strategic approaches at preclinical research level are stem cell-based therapy with genome editing and systemic mRNA therapy.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.58-62
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• 2006

Gaucher disease is an inherited disorder due to a deficiency in the activity of glucocerebrosidase (EC. 3.2.1.45) by genetic mutation which resulted from missense, nonsense, frameshift, deletion in long arm 21 of chromosome 1 (1q21). Gaucher disease is classified into the main three types as type 1 (nonneuronopathic), type 2 (acute neuronopathic) and type 3 (subacute neuronopathic) according to the progressive phase of manifestations and nervous system involvement. Gaucher disease patients had been treated by using the method as splenectomy and bone marrow transplantation. But enzyme replacement therapy as a more effective treatment has been available since the early 1990's. In order to treat Gaucher disease efficiently by using ERT, it is necessary to chase the progress of the therapy. In this study, therefore, we tried to chase the progress of the ERT by using the measurement of chitotriosidase activity in Gaucher disease patients.

• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.1
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• pp.11-13
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• 2018

In Malaysia, diagnosis and treatment of patients with mucopolysaccharidoses (MPS) is mainly localized at Hospital Kuala Lumpur, which is the national referral center for rare diseases. To date there are 83 patients diagnosed with MPS in our center, with MPS II being the commonest. The Malaysian National Medicines Policy second edition has a specific section on the orphan drugs which includes recombinant human enzyme for enzyme replacement therapy (ERT) in MPS. So far, National Pharmaceutical Regulatory Agency Malaysia has approved recombinant human enzyme for MPS types I (Loranidase), II (idursulfase), IVA (elosulfase alfa), and VI (Galsufase). Access to Idursulfase beta (another recombinant human enzyme for MPS II) and vestronidase alfa-vjbk (MPS VII) required special authorization on named patient basic. Currently there are 25 patients receiving ERT, 70% of the funding are from Ministry of Health (MOH), the remaining 30% are from various charitable funds and humanitarian programs. Thirteen newly diagnosed patients have to queue for an additional fund. Four patients have been treated with Hematopoietic stem cell transplant. MOH has also published guidelines regarding the patient selection criteria for ERT and treatment monitoring schedule.

• Clinical and Experimental Pediatrics
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• v.49 no.11
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• pp.1152-1157
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• 2006

Inherited metabolic disease is rare disorders that show symptoms mainly in pediatric age and early treatment is important for preventing complications of the disease. Recent development in molecular and biochemical techniques help clinicians with proper diagnosis of patients, however, many of the disease still remain lack of effective therapeutic strategies. Better understanding on biochemical and molecular basis of pathogenesis of the disease combined with advanced medical care would provide new sight on the disease that can also improve the quality of life and long-term prognosis of patients. Traditionally, there are several modalities in the treatment of metabolic diseases depend on the biochemical basis of the disease such as diet restriction, removing or blocking the production of toxic metabolites, and stimulating residual enzyme activity. The inherited metabolic disease is not familiar for many clinicians because the diagnosis is troublesome, treatment is complicated and prognosis may not as good as expected in other diseases. Recently, new therapeutic regimens have been introduced that can significantly improve the medical care of patients with metabolic disease. Enzyme replacement therapy has showed promising efficacy for lysosomal storage disease, bone marrow transplantation is effective in some disease and gene therapy has been trying for different diseases. The new trials for treatment of the disease will give us promising insight on the disease and most clinicians should have more interest in medical progress of the metabolic disease.

• Journal of mucopolysaccharidosis and rare diseases
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• v.3 no.2
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• pp.37-40
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• 2017

Mucopolysaccharidosis (MPS) is caused by accumulation of the glycosaminoglycans in all tissues due to decreased activity of the lysosomal enzyme. Patients exhibit multisystemic signs and symptoms in a chronic and progressive manner, especially with changes in the skeleton, cardiopulmonary system, central nervous system, cornea, skin, liver, and spleen. In the past, treatment of MPS was limited to enzyme replacement therapy (ERT). The outcome for affected patients improved with the introduction of new technologies as hematopoietic stem cell transplantation, relegated to specific situations after ERT became available. Intrathecal ERT may be considered in situations of high neurosurgical risk but still it is experimental in humans. New insights on the pathophysiology of MPS disorders are leading to alternative therapeutic approaches, as gene therapy, inflammatory response modulators and substrate reduction therapy. In this paper, we will highlight the recent novel treatment and clinical trials for MPS and discuss with the goal of fostering an understanding of this field.

• Journal of mucopolysaccharidosis and rare diseases
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• v.5 no.1
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• pp.1-7
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• 2021

Gaucher disease (GD, OMIM #230800 OMIM#230800) is a rare, autosomal recessive inherited metabolic disorder caused by mutation in GBA1 encoding the lysosomal enzyme, glucocerebrosidase. The deficiency of glucocerebrosidase leads to an accumulation of its substrate, glucosylceramide in macrophages of various tissues. Common clinical manifestations include cytopenia, splenomegaly, hepatomegaly, and bone lesions. The phenotype of GD is classified into three clinical categories: Type 1 (non-neuronopathic) is characterized by involvements on the viscera, whereas types 2 and 3 (neuronopathic) are associated with not only visceral symptoms but also neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 should be identified as they may be of prognostic value in some cases. Biomarkers including Chitotriosidase, CCL18, and glucosylsphingosine (lyso-GL1) are useful in diagnosis and treatment monitoring. Currently available disease-specific treatment in Korea consists of intravenous enzyme replacement therapy and substrate reduction therapy. For enhancing long-term prognosis, the onset of Parkinson's disease and Lewy body dementia, or the occurrence of a blood disease or cancer (hepatocellular carcinoma) should be monitored in older patients. The development of new strategies that can modify the neurological phenotype are expected, especially in Asia including Korea, where the prevalence of neuronopathic GD is relatively higher than that in western countries.

• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.1
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• pp.1-6
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• 2018

Lysosomal storage disorders are a group of rare inherited metabolic disorders with protean manifestations and variable severity ranging from attenuated forms to severe ones. It is necessary to diagnose and manage these disorders timely before irreversible damage occurs. Prior to the era of enzyme replacement therapy and newer therapeutics, only treatment option available was palliative care. Over the past two decades, extensive research in the lysosomal storage disorders has led to substantial expansion of our understanding about them. This mini review focusses on the spectrum, challenges faced in the diagnosis and therapy and remedial actions taken so far in lysosomal storage disorders in resource constrained country like India.