Targeting macrophages with baculovirus‐produced lysosomal enzymes: implications for enzyme replacement therapy of the glycoprotein storage disorder galactosialidosis

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Abstract
SPECIFIC AIMSLysosomal storage diseases (LSDs) are monogenic disorders of metabolism caused by deficiency of hydrolytic enzymes. Enzyme replacement therapy (ERT) is commercially available for some groups of patients with non-neuropathic forms of the disease, but most LSDs remain untreated. LSDs such as galactosialidosis (GS) in which the reticuloendothelial (RE) system is primarily involved could be treated efficiently by targeting the therapeutic enzyme exclusively to RE cells via the mannose receptor. Baculovirus-mediated production of recombinant enzymes in insect cells might be suitable and advantageous, because glycoproteins expressed in these cells carry mannosylated N-glycans and are poised to be internalized by cells that express the mannose receptor. GS is caused by a primary defect of the carboxypeptidase protective protein/cathepsin A (PPCA), but disease symptoms are primarily the result of a severe secondary deficiency of lysosomal neuraminidase (NEU1). The aim of this study was to determine w...
Funding Information
  • National Institutes of Health (DK-52025, GM-60950)
  • Assisi Foundation of Memphis
  • American Lebanese Syrian Associated Charities