Attempted enzyme replacement using human amnion membrane implantations in mucopolysaccharidoses.
Amnion membrane implantation has been proposed as an approach to enzyme replacement in mucopolysaccharidoses. Human amnion membranes have been subcutaneously implanted in the abdominal wall in 19 patients with mucopolysaccharidoses (MPS I, II and III). A protocol was developed for the objective evaluation of experimental treatments of these patients. Systematic evaluation of the clinical status before and 6 months after amnion membrane implantation reveals no change in function except improvement in joint mobility. The sum of all joint movements showed improvement from baseline values to 6 months after implantation by ANOVA followed by post-hoc analysis (p less than 0.056). The only specific joint movements to significantly improve after 6 months were shoulder extension (p less than 0.01) and hip internal rotation (p less than 0.05). Serial measurements of the deficient lysosomal enzyme activity in serum and white blood cells did not increase in any patient after amnion membrane implantation. Urinary glycosaminoglycan excretion decreased transiently in 2 of 10 patients after implantation, but a second amnion membrane implantation did not result in any change. Biopsy of the implantation site in 10 patients 6 months after amnion membrane implantation revealed a foreign-body reaction with giant cell formation and fibrosis and no recognizable amnion membrane tissue. We conclude that human amnion membrane implantation is not an effective therapy in mucopolysaccharidoses.
Muenzer
J
J
Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Neufeld
E F
EF
Constantopoulos
G
G
Caruso
R C
RC
Kaiser-Kupfer
M I
MI
Pikus
A
A
Danoff
J
J
Berry
R R
RR
McDonald
H D
HD
Thompson
J N
JN
D000009:Abdominal Muscles; D000293:Adolescent; D000650:Amnion / Q000201:enzymology / Q000637:transplantation*; D002648:Child; D002675:Child, Preschool; D016332:Fetal Tissue Transplantation; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007596:Joints / Q000503:physiopathology; D007962:Leukocytes / Q000201:enzymology; D009083:Mucopolysaccharidoses / Q000201:enzymology / Q000503:physiopathology / Q000601:surgery*
D006025:Glycosaminoglycans