title: Taliglucerase alfa leads to favorable bone marrow responses in patients with type I Gaucher disease.
abstract: Taliglucerase alfa (Protalix Biotherapeutics, Israel) is a carrot-cell-expressed recombinant human beta-glucocerebrosidase recently approved in the United States for the treatment of type 1 Gaucher disease (GD). As bone disease is one of the most debilitating features of GD, quantification of bone marrow involvement is important for monitoring the response to treatment. Therefore, bone marrow fat fraction (Ff) measured by quantitative chemical shift imaging (QCSI) was included as exploratory parameter to evaluate bone marrow response in treatment naïve GD patients participating in a double-blind, randomized phase III study. Eight GD patients with intact spleens were treated with 30 or 60U/kg biweekly. Ff results were compared to outcomes in 15 untreated Dutch GD patients with a follow-up interval of 1year. Five taliglucerase alfa treated patients had a Ff below the threshold that relates to complication risk (<0.23) at baseline (median (n=8) 0.19, range 0.11-0.35). Ff significantly increased compared to baseline (p=0.012) and compared to untreated patients (p=0.005), already after 1year of follow-up with further improvement up to 36months. In four patients with the lowest Ff, the higher dose resulted in increases above 0.23 within 1year. All patients had sustained improvements in all other parameters. There was no influence of antibodies on response parameters. Treatment with taliglucerase alfa results in significant increases in lumbar spine fat fractions, which indicates clearance of Gaucher cells from the bone marrow.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, the Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: van Dussen
authors.forename: A
authors.initials: A
authors.lastname: Zimran
authors.forename: E M
authors.initials: EM
authors.lastname: Akkerman
authors.forename: J M F G
authors.initials: JM
authors.lastname: Aerts
authors.forename: M
authors.initials: M
authors.lastname: Petakov
authors.forename: D
authors.initials: D
authors.lastname: Elstein
authors.forename: H
authors.initials: H
authors.lastname: Rosenbaum
authors.forename: D
authors.initials: D
authors.lastname: Aviezer
authors.forename: E
authors.initials: E
authors.lastname: Brill-Almon
authors.forename: R
authors.initials: R
authors.lastname: Chertkoff
authors.forename: M
authors.initials: M
authors.lastname: Maas
authors.forename: C E M
authors.initials: CE
authors.lastname: Hollak
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D056947:Enzyme Replacement Therapy / Q000009:adverse effects; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D057134:Antibodies, Neutralizing; D005962:Glucosylceramidase; C582473:taliglucerase alfa; C090568:imiglucerase