ARSA Human

Mutations in the ARSA gene can lead to a complete deficiency of the enzyme, resulting in a rare autosomal recessive lysosomal storage disorder known as Metachromatic Leukodystrophy (MLD) . MLD is characterized by the accumulation of sulfatides in the nervous system, leading to progressive neurological deterioration. Symptoms of MLD can include motor and cognitive decline, seizures, and eventually, loss of vision and hearing.

Recombinant human Arylsulfatase A (rhARSA) is a biotechnologically produced form of the enzyme, designed to mimic the structure and function of the natural human enzyme . This recombinant enzyme is produced using advanced genetic engineering techniques, often involving the expression of the human ARSA gene in cultured cells, such as mouse myeloma cell lines .

The production of rhARSA involves several steps:

1. Gene Cloning: The human ARSA gene is cloned into an expression vector, which is then introduced into host cells.
2. Protein Expression: The host cells are cultured under conditions that promote the expression of the ARSA protein.
3. Purification: The recombinant protein is purified using techniques such as affinity chromatography, ensuring a high level of purity (>95%) and low endotoxin levels (<1.0 EU per 1 μg of protein) .

Recombinant human ARSA is primarily being developed for the treatment of MLD. Clinical studies have shown that rhARSA can be administered intrathecally (directly into the cerebrospinal fluid) to deliver the enzyme to the central nervous system . This approach aims to reduce the accumulation of sulfatides and alleviate the symptoms of MLD.

Nonclinical studies have been conducted to compare different manufacturing processes of rhARSA. These studies evaluated the pharmacodynamic, pharmacokinetic, and safety profiles of rhARSA produced by different processes . The results indicated that changes in the manufacturing process did not significantly affect the enzyme’s activity, distribution, or safety .