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Lysosomal alpha-mannosidase and alpha-mannosidosis
Silvia Paciotti1, Michela Codini2, Anna Tasegian1
1Department of Medicine, Section of Neurology, University of Perugia, Sant'Andrea delle Fratte, 06132 Perugia, Italy.
Frontiers in Bioscience (Landmark Edition)
|November 5, 2016
Summary
Enzyme replacement therapy shows promise for alpha-mannosidosis, a rare genetic disorder. Recombinant human alpha-mannosidase can cross the blood-brain barrier, offering new hope for patients.
Area of Science:
- Biochemistry
- Genetics
- Enzymology
Background:
- Lysosomal alpha-mannosidase is crucial for oligosaccharide processing in human tissues.
- Mutations in the alpha-mannosidase gene cause alpha-mannosidosis, leading to toxic oligosaccharide accumulation.
- Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disease with significant clinical variability.
Purpose of the Study:
- To review scientific advancements in lysosomal alpha-mannosidase.
- To discuss the development of enzyme replacement therapy for alpha-mannosidosis.
- To highlight the potential of recombinant human alpha-mannosidase in treating this disorder.
Main Methods:
- Generation of a mouse model for alpha-mannosidosis.
- Production of recombinant human alpha-mannosidase using Chinese-hamster ovary cells.
- Clinical investigation of enzyme replacement therapy in patients with alpha-mannosidosis.
Main Results:
- Recombinant human alpha-mannosidase has been successfully produced.
- The recombinant enzyme demonstrated the ability to cross the blood-brain barrier at high doses.
- A randomized study initiated to evaluate the efficacy of enzyme replacement therapy in alpha-mannosidosis patients.
Conclusions:
- Enzyme replacement therapy is a promising therapeutic strategy for alpha-mannosidosis.
- Recombinant human alpha-mannosidase represents a potential therapeutic agent for this disease.
- Further research and clinical trials are essential to establish the full therapeutic potential.
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