Posts Categorized: Part 16: LYSOSOMAL DISORDERS



Beta-mannosidase gene mutations in autosomal dominant nystagmus

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A recent study in Genetics in Medicine aiming at the identification by whole-exome sequencing of genes involved in infantile nystagmus found heterozygous missense mutations in the MANBA gene, which the encodes lysosomal beta-mannosidase. The mutations resulted in decrease of ?-mannosidase activities in the patients as well as in mutant-transfected HEK293T cells. MANBA is expressed in the pretectal nucleus of the developing midbrain, […]



AAV gene therapy for Batten disease

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In this work, Beverly Davidson’s group investigated delivery of the gene encoding the soluble lysosomal enzyme tripeptidyl peptidase 1 (TPP1) enzyme to the ependymal cells in a dog model of a Batten disease.  They show that this strategy delayed disease onset, extended life span, and protected dogs from early cognitive decline, suggesting that this approach could improve the […]



Combined cysteamine bitartrate and N-acetylcysteine for NCL

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Levin et al (2014) recently reported on a study exploring the impact of combined oral cysteamine bitartrate (60 mg/kg per day) and N-acetylcysteine (60 mg/kg per day) in patients with neuronal ceroid lipofuscinosis (n=10, age range: 6 months to 3 years old). Assessments took place every 6-12 months until the patients had an isoelectric EEG […]



10-year follow-up study of ERT for MPS VI patients

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Giugliani R. Natural history and galsulfase treatment in mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome)-10-year follow-up of patients who previously participated in an MPS VI survey study. Am J Med Genet A. 2014 Aug;164(8):1953-64.   Giugliani et el evaluate the long-term effects of enzyme replacement therapy in Maroteaux-Lamy syndrome (MPS VI) by conducting a resurvey of […]



Chitotriosidase and Gaucher disease severity and progression

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van Dussen et al. Value of plasma chitotriosidase to assess non-neuronopathic Gaucher disease severity and progression in the era of enzyme replacement therapy. J Inherit Metab Dis. 2014 May 16. [Epub ahead of print] In a retrospective analysis of 80 patients with non-neuronopathic (type I) Gaucher disease, representing the majority of the cohort of such […]



Long-term effectiveness of enzyme replacement therapy in children with Gaucher disease

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Anderson LJ et al. Long-term effectiveness of enzyme replacement therapy in children with Gaucher disease: results from the NCS-LSD cohort study. J Inherit Metab Dis. 2014 Mar 18. [Epub ahead of print] In a longitudinal prospective and retrospective cohort study, Anderson et al investigated the effectiveness of enzyme replacement therapy in children with Gaucher disease. […]



Adjunct treatments for LSD therapy

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Enzyme replacement therapy and substrate reduction therapy  have had an incredible impact on the treatment of many lysosomal storage disorders (LSDs). However, in some LSDs the disorder continues to progress, in part due to downstream pathologic processes instigated by the storage material. Williams et al. Neurobiol Dis (2014) March (Epub) report that combination therapy  with miglustat, curcumin and ibuprofen provide […]



A universal biomarker for lysosomal storage disorders

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Lysosomal storage disorders (LSDs) occur at a frequency of 1 in every 5,000 live births. This study proposes Lysotracker a commercially available fluorescent probe to measure the relative acidic compartment volume of circulating B cells as a potentially universal biomarker for LSDs. This marker was validated in a mouse model of the LSD Niemann-Pick type C1 disease […]



A novel therapeutic target for Gaucher disease

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Gaucher’s disease (GD) due to mutations in the glucocerebrosidase gene (GBA) is divided into three clinical subtypes based on the absence (type 1) or presence (types 2 and 3) of neurological signs.  Glucosylceramide and glucosylsphingosine accumulation in the brain leads to massive neuronal loss in patients with neuronopathic GD (nGD). Vitner and colleagues found that modulating the receptor-interacting […]



Lysosomal enzyme protects against arthritis

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A recent work in the Journal of Clinical Investigation highlights the role of lysosomal enzymes for protection against arthritis. Lysosomal enzyme beta-glucuronidase (GUSB) was found as a key regulator of arthritis severity associated to Lyme disease that is caused by the spirochete Borrelia burgdorferi, the most prevalent arthropod-borne illness in the United States. Severely arthritic C3H […]