Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial.
Late-onset glycogen storage disease type 2 (GSD2)/Pompe disease is a progressive multi-system disease evoked by a deficiency of lysosomal acid alpha-glucosidase (GAA) activity. GSD2 is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. Since 2006 alglucosidase alfa has been licensed as a treatment in all types of GSD2/Pompe disease. We here present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 44 late-onset GSD2 patients with various stages of disease severity. Alglucosidase alfa was given i.v. at the standard dose of 20 mg/kg every other week. Assessments included serial arm function tests (AFT), Walton Gardner Medwin scale (WGMS), timed 10-m walk tests, four-stair climb tests, modified Gowers' maneuvers, 6-min walk tests, MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels and SF-36 self-reporting questionnaires. All tests were performed at baseline and every 3 months for 12 months of ERT. We found significant changes from baseline in the modified Gowers' test, the CK levels and the 6-min walk test (341 +/- 149.49 m, median 342.25 m at baseline; 393 +/- 156.98 m; median 411.50 m at endpoint; p = 0.026), while all other tests were unchanged. ERT over 12 months revealed minor allergic reactions in 10% of the patients. No serious adverse events occurred. None of the patients died or required de novo ventilation. Our clinical outcome data imply stabilization of neuromuscular deficits over 1 year with mild functional improvement.
Strothotte
S
S
Department of Neurology, Friedrich Baur Institute, Ludwig Maximilian University Munich, Munich, Germany.
Strigl-Pill
N
N
Grunert
B
B
Kornblum
C
C
Eger
K
K
Wessig
C
C
Deschauer
M
M
Breunig
F
F
Glocker
F X
FX
Vielhaber
S
S
Brejova
A
A
Hilz
M
M
Reiners
K
K
Müller-Felber
W
W
Mengel
E
E
Spranger
M
M
Schoser
Benedikt
B
D000328:Adult; D017668:Age of Onset; D000368:Aged; D003402:Creatine Kinase / Q000378:metabolism; D056947:Enzyme Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D044465:White People; D055815:Young Adult; D000520:alpha-Glucosidases / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D003402:Creatine Kinase; C509951:GAA protein, human; D000520:alpha-Glucosidases