Recombinant adeno-associated virus mediated gene transfer in a mouse model for homocystinuria

Area of Science:

• Biochemistry
• Genetics
• Medical Research

Background:

• Homocystinuria is a metabolic disorder resulting from cystathionine beta-synthase (CBS) deficiency.
• Clinical manifestations include intellectual disability, lens dislocation, vascular disease, and skeletal deformities.
• Current treatments like pyridoxine or methionine restriction are insufficient for long-term homocysteine level management.

Purpose of the Study:

• To investigate the potential of gene therapy as a novel treatment for homocystinuria.
• To evaluate the efficacy of a recombinant adeno-associated virus vector carrying human CBS cDNA (rAAV-hCBS) in a mouse model.

Main Methods:

• CBS-/- mice were administered rAAV-hCBS via intramuscular (IM) and intraperitoneal (IP) injections.
• Serum homocysteine levels were measured two weeks post-treatment.
• Lifespan and vector distribution/gene expression in organs were assessed.

Main Results:

• Serum homocysteine concentrations were significantly reduced in treated mice compared to controls.
• A modest increase in lifespan (3-7 days) was observed in treated CBS-/- mice.
• The rAAV-hCBS vector successfully transduced various organs, with detectable CBS gene expression in the liver.

Conclusions:

• Gene delivery via AAV vectors is effective in a mouse model of homocystinuria.
• AAV-mediated gene transfer demonstrates potential for treating homocystinuria.
• This study highlights gene therapy as a viable therapeutic strategy for this metabolic disorder.