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NEUROPHYSIOLOGICAL STUDY OF GENE THERAPY EFFECT ON MOUSE MODEL OF METACHROMATIC LEUKODYSTROPHY
Author(s) -
Amadio S.,
Trojani A.,
Del Carro U.,
Biffi A.,
Dolcetta D.,
Consiglio A.,
Martino S.,
Quattrini A.,
Bordig C.
Publication year - 2002
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2002.07011.x
Subject(s) - arylsulfatase a , metachromatic leukodystrophy , genetic enhancement , motor cortex , neurophysiology , nerve conduction velocity , transcranial magnetic stimulation , medicine , stimulation , neuroscience , endocrinology , pathology , biology , gene , biochemistry
Aim of the study : To evaluate with neurophysiological methods whether gene therapy may improve the abnormalities of motor system in mice with Metachromatic Leukodystrophy (MLD). Methods : 2 groups were studied: the first one consisted of 11 mice (AS2‐/‐) knocked‐out for Arylsulfatase A (ARSA) gene; the second one included 10 mice (AS2‐/‐tr) which, after lethal irradiation, were transplanted with autologous hematopoietic stem cells transducted with a retroviral vector containing the ARSA cDNA. Both groups underwent Motor Evoked Potentials (MEP) by transcranial electrical stimulation of motor cortex, as well as Motor Conduction Velocity (MCV) of ischiatic nerve and compared with a control group (n=11). Results : The mean latency of cortical MEP was shorter in AS2‐/‐tr than in AS2‐/‐ group of mice (4.9 ± 0.2 versus 6.8 ± 1.2 msec; p<0.001), being quite similar to controls (5.1 ± 0.4 msec). The mean MCV was higher in AS2‐/‐tr as compared to AS2‐/‐ group (27.1 ± 4.5 versus 22.8 ± 3.0 m/sec; p<0.05), even though significantly slower than controls (37.7 ± 3.8 m/sec). Comments : The neurophysiological data show that gene therapy seems to prevent ARSA deficient mice from developing a functional damage of corticospinal pathways. They also suggest that peripheral neuropathy has a slower course in mice treated with gene therapy, although motor nerve fibers are not completely spared.