Inventors: Jeffrey H. Grubb, William S. Sly
Summary: This invention is directed to chimeral fusion proteins having an IgG1 antibody Fc
portion and a lysosomal storage enzyme, particularly a Fc-GUS fusion protein useful
in treating Sly's disease in an embryo or fetus. The invention is also directed to
methods of treating in born errors of metabolism, particularly Sly's disease, in a
fetus by delivering to a pregnant mother a Fc-MPS enzyme fusion protein.
Recent advances in the medical arts have enabled enzyme replacement therapies (ERTs) for a number of metabolic diseases, especially lysosomal storage diseases (LSDs). Those diseases include Gaucher, Krabbe, Fabry and Pompe diseases, as well as various mucopolysaccharidoses (MPS). Of the MPS diseases, enzyme replacement therapies are currently available or under development for MPS I (Hurler Syndrome), MPS II Hunter Syndrome, MPS IV (Morquio Syndrome), MPS VI (Maroteaux-Lamy Syndrome), and MPS VII (Sly Syndrome). Some MPS disorders, including for example MPS VII, show evidence that significant storage of glycosaminoglycans has already begun in prenatal life. In fact, one of the most common manifestations of human MPS VII may be prenatal/neonatal hydrops resulting from beta-glucuronidase (GUS) deficiency in utero. Maternal IgG is known to be transported across the placenta into the fetal circulation by the neonatal Fc receptor (FcRn). This receptor recognizes the Fc domain of the IgG molecule and mediates transcytosis from maternal to fetal circulation.
Patents: U.S. patent 7,871,624