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Gaucher's disease is a rare disease that affects about 1 in 70 000 newborn children. It is characterized by a significant enlargement of the liver and spleen, fatigue, anemia, and decreased pulmonary function.

Dr. Roscoe Brady, a scientist at the National Institute of Health, was an expert on glycolipid metabolism. He discovered that symptoms of Gaucher's disease resulted from a deficiency of one specific enzyme, called α‐glucocerebrosidase [97]. This deficiency results in a disability to process glucocerebroside, which causes accumulation of this sphingolipid in various organs and tissues. In following work, he proposed to isolate the enzyme and treat the disease by injecting the human enzyme directly into patients. Brady developed an isolation protocol from human placenta and could demonstrate a significant lowering of glucocerebroside levels in the liver after intravenous injection of the enzyme [98]. It is noteworthy that reoccurrence of glucocerebrosides in the blood of the patient was relatively slow. However, it was quickly realized that this approach would not be a therapeutic option as, besides the short duration of the effect, isolated material from 40 placentae was required to treat 1 child with a single dose. Also, unfortunately, the isolation protocol could not be scaled up. After careful optimization of the isolation process, a facile deglycosylation strategy was developed to improve delivery of the glucocerebrosidase to macrophages, the location where a major fraction of the lipids was stored. Enriching the mannose content in the glycoside chains by treatment with exo‐glycosidases resulted in a significantly more effective preparation [99].

In 1981, Sherdian Snyder, George M. Whitesides (Harvard University), and Henry Blair founded a company called Genzyme, dedicated to produce modified enzymes to provide them to the NIH for testing in clinical trials. Brady formed a relation with Blair, and Genzyme decided to start producing the enzyme required for clinical trials.

The first product, Ceredase™ (alglucerase), was still isolated from placentae, which required industrial scale purification and deglycosylation capacities. One year of treatment of a single patient required isolation of enzyme from 50 000 placentae. Finally, recombinant production of the enzyme, differing in only one position from placenta‐derived protein could significantly simplify this process, also glycoengineering resulted in direct production of the optimized mannose‐bearing oligosaccharide side chains. This product was named Imiglucerase (Cerezyme™).

Genzyme became a leading company in enzyme replacement therapy with the development of treatment options for lysosomal storage disorders being a cornerstone of its research. In 2011, Genzyme was acquired by Sanofi for US$ 20.1 billion. The detailed history of the development of enzyme replacement therapy for Gaucher's disease is described in more detail by Brady [100] and Deegan [101].