Lh. Oconnor et al., ENZYME REPLACEMENT THERAPY FOR MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII LEADS TO IMPROVEMENTS IN BEHAVIOR AND AUDITORY FUNCTION, The Journal of clinical investigation, 101(7), 1998, pp. 1394-1400
Mucopolysaccharidosis type VIP (MPS VII; Sly syndrome) is one of a gro
up of lysosomal storage diseases that share many clinical features, in
cluding mental retardation and hearing loss, Lysosomal storage in neur
ons of the brain and the associated behavioral abnormalities character
istic of a murine model of MPS VII have not been shown to be corrected
by either bone marrow transplantation or gene therapy, However, intra
venous injections of recombinant beta-glucuronidase initiated at birth
reduce the pathological evidence of disease In MPS VII mice, In this
study we present evidence that enzyme replacement initialed at birth i
mproved the behavioral performance and reduced hearing loss in MPS VII
mice, Enzyme-treated MPS VII mice performed similarly to normal mice
and significantly better than mock-treated it?PS VII mice in every pha
se of the Morris Water Maze test, In addition, the auditory function o
f treated MPS VII mice was dramatically improved, and was Indistinguis
hable from normal mice, These data indicate that some of the learning,
memory, and hearing deficits can be prevented in MPS VII mice if enzy
me replacement therapy is initiated early in life, These data also pro
vide functional correlates to the biochemical and histopathological im
provements observed after enzyme replacement therapy.