Gaucher Disease

Gaucher Disease is one of the lysosomal storage disorders. These disorders are due to a deficiency of a single enzyme required for the metabolism of lipids, glycoproteins (sugar containing proteins) or mucopolysaccharides, resulting in an excess of products destined for breakdown and recycling being stored in the cell. In Gaucher disease, mutations in the gene for glucocerebrosidase result in accumulation of glucocerebroside in the spleen, liver, lungs, bone marrow, and sometimes in the brain. The most severe form of this disease causes severe brain problems, and death by 2 years of age.

Status

For the less severely affected patients, enzyme replacement therapy is available, in which the purified enzyme (glucocerebrosidase) is infused intravenously into patients. This helps reverse symptoms caused by organ damage, but does not help the neurological effects. Gene therapy for Gaucher disease involves delivering a normal copy of the glucocerebrosidase gene to the liver, allowing the liver to secrete enough enzyme to ameliorate symptoms without the need for repetitive infusion. ReGenX’s AAV Vector Technology includes novel AAV serotypes that are significantly more efficient in delivering genes to the liver than other serotypes, and more efficient than other gene therapy delivery systems such as lentivirus. These serotypes result in sustained high level expression of the therapeutic enzyme, which may be more efficacious than the changing levels of enzyme achieved by periodic infusions of purified protein. The proposed therapeutic is in the research stage of development.

By substituting the appropriate gene, the same approach to treating Gaucher Disease is expected to be efficacious in treating other lysosomal storage disorders, including Fabry Disease and Pompe Disease.

Market

Gaucher disease occurs in less than 1 in 50,000 newborns. While individually most lysosomal storage disorders are rare, as a group their incidence is about 1 in 5,000 live births.¹ The carrier rate for the mutations which cause Gaucher Disease may be as high as 1 in 15 Jewish people of Eastern European ancestry, and 1 in 100 of the general population.² Current enzyme replacement therapeutics can cost over $100,000 per year.³