Jan. 9, 2007 -- By all expectations, it shouldn't have worked as well as it did. A combination of bone marrow transplantation and gene therapy greatly lengthened the lives of laboratory mice doomed by a rapidly progressing, fatal neurodegenerative disorder also found in people.
The Washington University School of Medicine in St. Louis researchers who made the discovery set out with low hopes for the combination therapy because on its own, each treatment was only modestly effective for the sick mice.
The mice are called Twitcher mice because the damage that happens in their nervous systems results in twitching. In people, the same genetic defect causes Krabb disease, or globoid-cell leukodystrophy, an inherited disorder that destroys both the brain and the nerves of the body.
"We had everything we needed to test the combination treatment, so we said, 'Let's just give it a try,'" says the study's senior author, Mark Sands, Ph.D., associate professor of medicine and of genetics. "Alone, these therapies resulted in a small survival benefit, but with the combination we were seeing mice with dramatically extended life spans. Ninety-five percent of the Twitcher mice that had the combination treatment were still alive after all the other Twitcher mice had died."
The researchers gave newborn Twitcher mice injections of a gene therapy vector into the brain and infused them with bone marrow from healthy mice. Mice receiving the dual therapy lived more than twice as long (greater than 100 days), on average, as untreated mice or those given a single therapy and had improved motor skills. The research is reported in the January issue of Molecular Therapy.
Although not considered a cure at this stage, the combination therapy offers hope for treatment of diseases like Krabb, which are termed lysosomal storage diseases. These disorders include Niemann-Pick and Tay-Sachs diseases and affect 1 in 5,000 children born each year.