All patients had urine GAG levels and enzyme activity of GALNS. Urine KS levels were available in 10 patients.
Suspicion of MPS IVA may be supported by quantitative and/or qualitative testing of urinary GAG levels demonstrating increased levels and presence of KS, but diagnosis requires confirmation of GALNS deficiency in white blood cells or fibroblasts, or mutation analysis showing the presence of pathogenic mutations in both alleles (20,21).
With regard to the previously determined optimum pH for the other enzyme substrates (22, 26), the multiplex assay pH was adjusted to pH 5.0 to ensure that all 7 enzymes had activity within a sufficient analytical range, with a particular regard to the least active GALNS (8).
The assays were performed in 96-well microtiter plates in 50 mmol/L ammonium acetate buffer (pH 5.0) with an assay cocktail consisting of substrates at the following concentrations: TPP1 (0.2 mmol/L), I2S (1.0 mmol/L), NAGLU (0.5 mmol/L), GALNS (1.0 mmol/ L), ARSB (1.0 mmol/L), and GUSB (0.5 mmol/L).
We believe that additional manufacturing capabilities beyond our current resources will be needed to support anticipated peak sales for GALNS
, PEG-PAL for PKU, BMN 701 for Pompe disease, BMN 111 for achondroplasia, if they continue to progress to approval, and our other preclinical programs."
El plasmido pAAV-CMV-GALNS, previamente construido , porta el ADNc de la GALNS humana bajo el control del intensificador temprano y el promotor del citomegalovirus, un intron sintetico, la senal de entrada al ribosoma IRES, que permite la transduccion de dos secuencias en un mismo ARNm, el gen de resistencia a neomicina y la senal de poliadenilacion de la hormona de crecimiento bovina, flanqueados por los ITR del serotipo AAV2.
El medio de cultivo se remplazo por medio fresco dos horas antes y las celulas fueron transfectadas con 1,5 x [10.sup.10] gv en una relacion 1:1 y 1:2 GALNS: SUMF1.
The method used for the synthesis of the GALNS
substrate (GALNS-S) and the GALNS
internal standard (GALNS-IS) has recently been described (6).
30 November 2011 - BioMarin Pharmaceuticals (NASDAQ:BMRN) said on Tuesday that it had launched its Phase II study for GALNS
(N-acetylgalactosamine 6-sulfatase) in patients under five years of age with mucopolysaccharidosis IVA (MPS IVA).
5 February 2010 - US-based BioMarin Pharmaceutical Inc (NASDAQ: BMRN) gave an update yesterday on the Phase I/II study for BMN 110 or N-acetylgalactosamine 6-sulfatase (GALNS
), intended for the treatment of the lysosomal storage disorder Mucopolysaccharidosis Type IVA (MPS IVA), or Morquio A Syndrome.
M2 EQUITYBITES-March 9, 2012-BioMarin Pharmaceutical Inc enrols patients for Phase 3 study of GALNS
for Morquio A Syndrome(C)2012 M2 COMMUNICATIONS http://www.m2.com
M2 EQUITYBITES-November 30, 2011-BioMarin Pharmaceutical Inc commences Phase 2 study of GALNS
for MPS IVA treatment(C)2011 M2 COMMUNICATIONS http://www.m2.com