Cutting Edge: Enzyme replacement therapy holds out hope for kids with rare disease

The All India Institute of Medical Science (AIIMS) Mangalagiri has successfully treated a child with a rare disease called Mucopolysaccharidosis Type I (MPS-I) with an enzyme replacement therapy, the first to be adminered in Andhra Pradesh.
Mucopolysaccharidosis type I (MPS I) is a rare disease in which the body does not have enough of an enzyme needed to break down long chains of sugar molecules. These chains of molecules are called glycosaminoglycans (formerly called mucopolysaccharides). As a result, the molecules build up in different parts of the body and cause various health problems.
“MPS-1 is a rare metabolic disease with an estimated incidence of one in every 1,00,000 births. This disease occurs due to the deficiency of the L-iduronidase enzyme, which is required for breaking down an endogenous complex carbohydrate known as Glycosaminoglycans (CAG). The deficiency of this enzyme leads to accumulation of GAG fragments inside the lysosomes of each human cell leading on to symptoms. MPS-1 is a severe, progressive disorder with involvement of multiple organs and tissues that results in premature death, usually 10 years of age without treatment,” said Dr Arun Babu T, Additional Professor Pediatrics at AIIMS Mangalagiri.
What have been the treatment options so far?
He added there were other options and cures, including bone marrow transplants, but not every child is eligible for this treatment as it can be done only when a donor is available. “Bone marrow transplantation is curative in some children if done early, before two years of age. For most others, the main treatment is lifelong enzyme replacement therapy. In this therapy, the deficient enzyme is given exogenously as injections at frequent intervals,” he added.
What is Enzyme Replacement Therapy?
This is a medical treatment which replaces an enzyme deficient or absent in the body. The therapy includes giving the patient a periodic intravenous (IV) infusion of a solution containing the enzyme. ERT is available for some lysosomal storage diseases, including Gaucher disease, Fabry disease, MPS I, MPS II (Hunter syndrome), MPS VI and Pompe disease.
According to Dr Arun, the therapy does not help you get rid of the underlying genetic defect but it increases the concentration of the enzyme that the patient is lacking. It is a lifelong process but high doses are required during childhood till 15 years of age. The doses gradually reduce once the risk factors decrease.
ERT has also been used to treat patients with severe combined immunodeficiency (SCID) resulting from an adenosine deaminase deficiency (ADA-SCID). Other treatment options for patients with enzyme or protein deficiencies include substrate reduction therapy, gene therapy and bone-marrow derived stem cell transplantation.
How does it work?
According to a journal published in the US-based National Library of Medicine, the major proportion of the infused recombinant enzymes for MPS is delivered to the visceral organs such as the liver, kidney, and spleen. “The infused enzymes have a short half-life in the circulation due to rapid binding to M6P receptors and uptake into visceral organs. It is known that only a small fraction of the recombinant enzyme can reach the bone cartilage and the eye, explaining why improvements of these organs/systems are limited even after long-term treatment. Moreover, due to the inefficacy of recombinant enzymes to cross the blood–brain barrier (BBB), there are no benefits of ERT for central nervous system (CNS) involvement,” said the journal.
Why are drugs not accessible?
Dr Arun adds that ERT drug for MPS-1 is known as Aldurazyme and is manufactured Genzyme Sanofi Pharmaceuticals in India. He says that the expensive treatment of the rare disease makes it difficult for a middle class or poor family to get the treatment and can cost Rs 85 lakh per year.
“This drug is extremely costly and priced at Rs 69,000 per vial. For our child, the entire cost of treatment for one year was approximately Rs 85 lakh and was being funded ESI hospital Vijayawada under the ESI scheme. However, not all children with rare diseases are that fortunate. “Rare diseases are often a neglected area in paediatrics. Diagnosis and treatment of ‘rare diseases’ are challenging due to unavailability of diagnostic tests and high costs of treatment. Establishing a system for treating poor children with rare diseases in government hospitals is the need of the hour,” Dr Arun adds.
He added that the child was lucky to get funding from ESI hospital as not many companies are investing much on the research and development of the enzyme to make it cost-effective.