Lysosomal alpha-mannosidase and alpha-mannosidosis.
Lysosomal alpha-mannosidase with acidic pH optimum is ubiquitous in human tissues where is expressed in two major forms, A and B that are the product of a single gene located on chromosome 19. Mutations in the gene encoding for alpha-mannosidase cause alpha- mannosidosis, an autosomal recessive disease, resulting in the accumulation of unprocessed mannose containing oligosaccharide material. This rare disease has an estimated incidence of 1/500.0.00 live births and clinically is divided into three subgroups. Today the most promising therapy for this disease is the enzyme replacement therapy. To develop this strategy a mouse model for alpha-mannosidosis has been generated and a recombinant human alpha-mannosidase has been produced from Chinese-hamster ovary cells. Interestingly it has been shown that the recombinant enzyme, used in high dose, can cross the blood brain barrier. This recombinant enzyme has been tested in the first randomized study investigating the efficacy of enzyme replacement therapy in patients with alpha-mannosidosis. This review contains the scientific progresses on lysosomal alpha-mannosidase from the cloning to the beginning of the therapy.
Department of Medicine, Section of Neurology, University of Perugia, Sant'Andrea delle Fratte, 06132 Perugia, Italy.
Silvia
S
Paciotti
Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti 48, 06123 Perugia, Italy.
Michela
M
Codini
Department of Medicine, Section of Neurology, University of Perugia, Sant'Andrea delle Fratte, 06132 Perugia, Italy.
Anna
A
Tasegian
Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti 48, 06123 Perugia, Italy.
Maria Rachele
MR
Ceccarini
Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti 48, 06123 Perugia, Italy.
Samuela
S
Cataldi
Department of Experimental Medicine, University of Perugia, Polo Unico Sant'Andrea delle Fratte, Piazzale Gambuli, 06132 Perugia, Italy.
Cataldo
C
Arcuri
Department of Chemistry, Biology and Biotechnology, Via Elce di sotto, 06123, Perugia, Italy.
Bernard
B
Fioretti
Laboratory of Nuclear Lipid BioPathology, CRABiON, Perugia 06122, Italy.
Elisabetta
E
Albi
Department of Pharmaceutical Science, University of Perugia, Via Fabretti 48, 06123 Perugia, Italy, tommaso.beccari@unipg.it.
Tommaso
T
Beccari
D000818:Animals; D004195:Disease Models, Animal; D056947:Enzyme Replacement Therapy; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D009154:Mutation; D011994:Recombinant Proteins / Q000627:therapeutic use; D043323:alpha-Mannosidase / Q000235:genetics* / Q000378:metabolism* / Q000627:therapeutic use; D008363:alpha-Mannosidosis / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*
D011994:Recombinant Proteins; D043323:alpha-Mannosidase