Treatment for Pelizaeus-Merzbacher Disease

Although Dr. Klaus-Armin Nave, Department of Neurogentics, Max-Planck-Institute of Experimental Medicine, was unable to attend the meeting in Ft. Worth, his pre-clinical work on a treatment for Pelizaeus-Merzbacher disease was presented by his colleague, Dr. Celia Kassmann.

Investigators in Dr. Nave’s lab are using a mutant mouse model to test a new drug therapy for Pelizaeus-Merzbacher disease (PMD). This severe leukodystrophy characterized by ataxia, mental retardation, epilepsy and premature death. No therapy is currently available. Like most humans with PMD, Dr. Nave’s mutant mice over-express the Plp1 gene. So, the mice were used to test the effect of a new drug (ZK230211) on Plp1 gene expression. Motor function ws measured during the 10 week trial. At the end of the trial, Plp1 gene expression was measured in the brains of the mice. The treated animals expressed 15% less Plp1 than the control mutant mice. Importantly, ZK230211-treated mutants had significantly better motor control. Most relevant, there were about 30% more myelinated axons in the corticospinal tract of treated mutants, as compared to the controls. This "proof of principle" trial suggests that it is possible to develop a ‘rational drug therapy’ for PMD patients having Plp1 gene duplications.