Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk.
Van den Hout JM, Kamphoven JH, Winkel LP, Arts WF, De Klerk JB, Loonen MC, Vulto AG, Cromme-Dijkhuis A, Weisglas-Kuperus N, Hop W, Van Hirtum H, Van Diggelen OP, Boer M, Kroos MA, Van Doorn PA, Van der Voort E, Sibbles B, Van Corven EJ, Brakenhoff JP, Van Hove J, Smeitink JA, de Jong G, Reuser AJ, Van der Ploeg AT
Pediatrics, 2004 May
Abstract
Recent reports warn that the worldwide cell culture capacity is insufficient to fulfill the increasing demand for human protein drugs. Production in milk of transgenic animals is an attractive alternative. Kilogram quantities of product per year can be obtained at relatively low costs, even in small animals such as rabbits. We tested the long-term safety and efficacy of recombinant human -glucosidase (rhAGLU) from rabbit milk for the treatment of the lysosomal storage disorder Pompe disease. The disease occurs with an estimated frequency of 1 in 40,000 and is designated as orphan disease. The classic infantile form leads to death at a median age of 6 to 8 months and is diagnosed by absence of alpha-glucosidase activity and presence of fully deleterious mutations in the alpha-glucosidase gene. Cardiac hypertrophy is characteristically present. Loss of muscle strength prevents infants from achieving developmental milestones such as sitting, standing, and walking. Milder forms of the disease are associated with less severe mutations and partial deficiency of alpha-glucosidase.