Attempted enzyme replacement using human amnion membane implantations in mucopolysaccharidoses

Abstract

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.

Enzyme replacement therapy for mucopolysaccharidosis VI: A phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study

“…Access to better medical care may also have contributed to the improved outcomes, as documented with gains in joint ROM in a treatment study for MPS I. 20 Infusions with rhASB were well tolerated. The majority of the patients experiencing IARs did have high levels of IgG antibody, although there were many exceptions.…”

A retrospective audit of anesthetic techniques and complications in children with mucopolysaccharidoses

“…This procedure attempted to replace enzyme function by subcutaneous implantation of amnion membrane in patients with MPS. Unfortunately, amnion transplants do not produce long‐term correction of lysosomal enzyme deficiencies and no change in organ function (14). Mahoney (10) and Walker (15) have commented that regression of soft tissue deposits following HSCT has not been associated with any reduction in the incidence of difficult intubation.…”

Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment

“…It has allowed an increased IDS activity to be detected, but unfortunately without any clinical benefits. Amnion membrane implantation was evaluated, but without success [182]. In 2005, thanks to the availability of the mouse model, another cell therapy study was conducted [183].…”