Improved myelination in nerve grafts from the leucodystrophic twitcher into trembler mice: evidence for enzyme replacement.

The possibility of the treatment of globoid cell leucodystrophy in the twitcher mouse by enzyme replacement was investigated using nerve grafts from affected animals into trembler hosts. The trembler mouse has no known enzyme deficiency but its peripheral nerves are hypomyelinated due to a Schwann cell abnormality and this defect represents a marker used in the present study to exclude the possibility of migration of Schwann cells from the host into the graft. Twitcher grafts were examined after periods ranging from 1 to 4 months. At all stages myelin sheaths were well formed and did not show signs of degeneration. Moreover the interstitial oedema, characteristic of the twitcher nerve, was greatly diminished in amount and no globoid cells were seen. These results were compared with previous studies done in vivo and in vitro in other types of lysosomal storage disease. We concluded that the improvement of the conditions of the myelin in the transplant is possibly due to enzyme replacement from the host.