Human Alpha Galactosidase A Coding Sequence for the Treatment of Fabry Disease

Fabry disease is a rare lysosomal disorder, caused by mutations in the Alpha galactosidase (GLA) gene. Enzyme Replacement Therapy (ERT) and more recently, Chaperon Therapy products, have seen some success in the treatment of Fabry diseases. However, their high cost encourages the need for novel, more efficient and cheaper treatments. It has now been generated a codon optimized cDNA sequence expressing human GLA able to more efficiently produce in vivo the enzyme.

A non‐integrative vector can be administered to juvenile and adult subjects.
An integrative vector can be administered to neonatal and young patients.
The vector may be used alone or in combination with other treatments or components of the treatment, i.e. enzyme replacement therapies or oral chaperone therapies.
The vector can be delivered to the liver by intravenous injection.

A new coding sequence for human GLA has been identified, together with vectors, plasmids, host cells and pharmaceutical compositions including such sequence. In particular, the use of this sequence advantageously improves GLA enzyme translation of about 4‐6 fold over the wild‐type sequence coding for GLA. A galactosidase A deficiency is corrected by the reduction in lyso‐Gb3 levels in plasma and tissue achieved through expression of the GLA enzyme in the liver. Vectors may be administered to a patient. An integrative vector can be administered to a neonatal or young subject together with a vector expressing a nuclease, such as Cas9, or together with one or more drugs enhancing gene targeting rate; this advantageously allows to treat Fabry disease at its early stages by integrating the functioning GLA coding sequence into the genome of the subject.

Treatment of Fabry Disease.
Gene therapy.
Pharmaceutical sector.