Hurler syndrome

Genzyme (1 Kendall Square, Cambridge, MA 02139-1562; Tel: 617/252- 7500) and BioMarin Pharmaceutical (11 Pimental Court, Novato, CA 94949; Tel: 415/382-6653) are forming a joint venture to develop and commercialize BioMarin's lead product, alpha-L-iduronidase, a recombinant enzyme for the treatment of the genetic disorder known as mucopolysaccharidosis I (MPS I). The best known and most severe form of MPS I, Hurler syndrome, is a crippling and fatal disease that affects young children. Terms of the proposed joint venture were not disclosed.

BioMarin initiated a pivotal clinical trial of alpha-L-iduronidase in January 1998, following the collection of positive preclinical data. All of the trial's 10 patients have begun treatment, and the company expects the study to conclude by July 1998. BioMarin received orphan drug designation for alpha-L-iduronidase in September 1997, which would allow exclusive marketing of the product for seven years following FDA clearance.

Characterized by a halt in a patient's physical and mental development, MPS I is caused by lack of an active enzyme, alpha-L- iduronidase, which results in a build-up of certain carbohydrate materials in all parts of the body. The debilitating effects of MPS I can include enlargement of the liver and spleen, skeletal deformity, vision impairment, stunted growth, hearing loss, and fluid on the brain. MPS I is comprised of a spectrum of disorders known as Hurler, Hurler-Schei, and Schei syndromes.

Approximately 2,000-3,000 people in the developed world have been diagnosed with MPS I. As with other lysosomal storage diseases, there are believed to be many more undiagnosed patients. There is currently no known effective treatment for MPS I. Bone marrow transplants are currently the only therapeutic option and can improve some symptoms. However, bone marrow transplants are available to only a small subset of patients and are expensive, painful, and potentially harmful.

BioMarin's clinical trial to treat MPS I is being conducted at the University of California-Los Angeles. Emil Kakkis and Elizabeth Neufeld, two of the foremost researchers in the field of MPS I, are leading the study. Neufeld and her colleagues were responsible in the 1970s for identifying the deficient enzyme that causes MPS I. Neufeld's early studies at the National Institutes of Health established the conceptual basis for treating MPS I using enzyme replacement therapy. Neufeld and Kakkis developed a method for producing the recombinant form of alpha-L-iduronidase.

In a preclinical study conducted at UCLA, treatment of dogs with alpha-L-iduronidase over a 13-month period slowed the progression of MPS I. The study showed an uptake of the enzyme in the animals, which resulted in decreased lysosomal storage in the liver, kidney, spleen, lymph nodes, and lungs. Furthermore, the treated dogs gained more weight, were more active, and had less joint stiffness than the untreated dogs.

Genzyme already has a stake in enzyme replacement therapy. It supplies glucocerebrosidase ("Ceredase" is the placental extract version, "Cerezyme" is the recombinant version) for the treatment of Gaucher's disease, which is a lysosomal storage disorder caused by a lack of the particular enzyme.

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