Methods for treating lysosomal acid lipase deficiency in patients
The present invention provides methods of treating LAL deficiency comprising administering to a mammal a therapeutically effective amount of lysosomal acid lipase with an effective dosage frequency. Methods of improving growth and river function, increasing LAL tissue concentration, and increasing LAL activity in a human patient suffering from LAL deficiency are also provided.
1. An isolated recombinant human lysosomal acid lipase (rhLAL) as set forth in SEQ ID NO: 1 that contains N-linked glycans attached to Asn 15 , Asn 80 , Asn 140 , Asn 252 and Asn 300 , wherein the N-linked glycans comprise bi-, tri- and tetra-antennary structures with N-acetylglucosamine (GlcNAc), mannose and/or manose-6-phosphate (M6P), and wherein the rhLAL comprises M6P-containing glycans at Asn 80 , Asn 140 and Asn 252 .
2. The isolated rhLAL of claim 1 , wherein the rhLAL does not contain sialic acid.
3. The isolated rhLAL of claim 1 , wherein the rhLAL has a molecular weight of about 55 kD.
4. The isolated rhLAL of claim 1 , wherein the rhLAL has a specific activity of at least about 100 U/mg.
5. The isolated rhLAL of claim 1 , wherein the rhLAL does not comprise O-linked glycans.
6. The isolated rhLAL of claim 1 , wherein Asn 51 of the rhLAL is not glycosylated.
7. The isolated rhLAL of claim 1 , wherein the rhLAL has serum half-life (t 1/2 ) that is less than 40 minutes.
8. The isolated rhLAL of claim 1 , wherein the N-linked glycans do not comprise fucose and the rhLAL does not contain O-linked glycans.
9. A method of treating a human subject with a lysosomal acid lipase (LAL) deficiency comprising administering the isolated recombinant human LAL of claim 1 to the subject.
10. A method of increasing LAL activity in a human subject with a LAL deficiency comprising administering the isolated recombinant human LAL of claim 1 to the subject.