Alpha-Mannosidosis: Therapeutic Strategies

Area of Science:

• Biochemistry
• Genetics
• Medical Genetics

Background:

• Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder.
• It results from mutations in the gene encoding lysosomal α-d-mannosidase.
• No genotype-phenotype correlation is observed in alpha-mannosidosis.

Purpose of the Study:

• To review the genetics of alpha-mannosidosis.
• To discuss therapeutic strategies including bone marrow transplantation and enzyme replacement therapy (ERT).
• To present clinical outcomes of ERT in alpha-mannosidosis patients.

Main Methods:

• Review of genetic variants and biochemical characterization.
• Analysis of outcomes from bone marrow transplantation.
• Evaluation of Phase I-II and Phase III studies on recombinant enzyme therapy.

Main Results:

• 155 variants identified in 191 patients.
• Bone marrow transplantation is indicated for neurocognitive preservation and preventing early death.
• Recombinant enzyme therapy demonstrated positive clinical effects in clinical trials.

Conclusions:

• Enzyme replacement therapy is a key treatment for alpha-mannosidosis.
• Recombinant enzyme therapy offers a positive clinical effect for patients.
• Further research into therapeutic strategies is ongoing for this rare disease.