Therapy
- Enzyme replacement therapy (ERT) for Morbus Morquio (Mucopolysaccharidosis (MPS IVA)
Therapy Approach
Enzyme Replacement Therapy (ERT)
Enzyme replacement therapy (ERT) is a therapeutic approach for a genetic disorder whereby the protein, naturally lacking, is manufactured separately and given intravenously to the patient on a regular basis. It is an established strategy for treating lysosomal storage diseases (LSDs) and is clinically available or in clinical trials for several other LSDs.
Current and Future Treatment Options
Currently, there is no effective therapy for MPS IVA, and most attempts at therapy are palliative in nature and focused on management of the clinical symptoms. Bone marrow and cord blood transplantation have been utilized in an attempt to deliver functional enzyme activity. Bone marrow transplantation is recommended for patients with MPS I (Hurler, Hurler-Scheie, or Scheie Syndromes), but is not recommended for patients with the severe form of MPS IVA. Lysosomal enzyme trafficking makes intravenous N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme replacement therapy a feasible therapeutic strategy: GALNS is a monomeric glycoprotein containing 522 amino acids and 2 potential N-linked glycosylation sites. GALNS is sialylated and contains mannose-6-phosphate (M6P) residues, which target the protein to its site of action in the lysosome. The M6P moiety binds to a specific M6P receptor in the Golgi and is thus directed to prelysosomal compartments. Enzymes that escape this routing system are secreted by the cell via the constitutive secretory pathway and are often recaptured by cell surface M6P receptors that return the GALNS to the lysosome by the endocytic pathway.
In recent studies of enzyme replacement therapy in animal models with lysosomal storage diseases, cellular and humoral immune responses to the injected enzymes have been recognized as major impediments to effective treatment. To study the long-term effectiveness and side effects of therapies in the absence of immune response, Tomatsu et al developed an MPS IV A mouse model, which has many similarities to human MPS IV A and is tolerant to human GALNS protein. . This mouse model should provide a good model to evaluate long-term administration of enzyme replacement therapy (ERT) with GALNS in patients with MPS IVA, which will offer the possibility of a safe and efficacious approach for the future treatment of this disease.
Product Design
Vivendy Therapeutics Ltd. has developed a specific recombinant human N-acetylgalactosamine-6-sulfatase (rhGALNS) that is specifically modified to improve enzyme activity - enhancing the efficacy of the therapy in MPS IVA significantly.
Vivendy Therapeutics Ltd. holds a world wide exclusive licence on IP containing a pharmaceutical composition, a fusion protein and a method for MPS IVA ERT. Additionally, own IP on enhancing enzyme activity is filed with the application pending.