Prenatal enzyme replacement therapy for hypophosphatasia
Transplacental enzyme replacement therapy (ERT) is disclosed for deficiency of a polypeptide such as a tissue-nonspecific alkaline phosphatase (TNSALP) by administering a pharmaceutical composition that comprises a water-soluble TNSALP portion, e.g., C-terminus-truncated TNSALP peptide-bonded to an IgG1 antibody Fc portion, to a pregnant animal whose fetus or embryo is in need of such therapy. Also contemplated is a method for treating a metabolic disorder, such as HPP, in a fetus or embryo where a fusion protein that comprises a Fc fragment of an IgG1 antibody peptide-bonded to TNSALP is administered to a pregnant mother. The protein crosses the placenta of the mother and enters the fetal blood stream. The protein is taken up into fetal tissue such that the TNSALP restores normal metabolic activity in the fetus.
1. A method for treating hypophosphatasia in a fetus or embryo comprising the step of parenterally delivering a fusion protein having the sequence as set forth in SEQ ID NO:2 to a pregnant mother, wherein said fusion protein comprises a Fc fragment of an IgG antibody and a tissue-nonspecific alkaline phosphatase enzyme, and wherein said fusion protein crosses a placenta of said mother and enters said fetus's or embryo's blood stream, and wherein said fusion protein is taken up into fetal or embryonic tissue such that said enzyme restores normal mineralization activity in said fetus or embryo.
2. The method of claim 1 , wherein said fusion protein is delivered intraperitoneally or subcutaneously.