Alexander disease which was first described in 1949 is assumed to be triggered due to mutations in the glial fibrillary acidic protein (GFAP) gene. The disorder typically affects newborns and children. Apparently scientists from the University of Wisconsin-Madison have found various compounds that can be employed to treat the rare and fatal neurological disorder. After using unique screens, a set of FDA-approved drugs known to compress the overproduction of a brain protein which is a key player in the disorder were observed.
The latest research undertaken from the past five years, seem to provide an ease for patients with congenital brain disease treated using present day drugs. Less than 300 people around the world have been registered with this disease that is known to encode the production of the GFAP protein. The investigators ascertain that GFAP is present in the normal central nervous system also, yet its function is not analyzed in detail.
Messing, Waisman Center researcher and a professor of comparative biosciences in the UW-Madison School of Veterinary Medicine affirmed, “What we are hoping for is something we can use to manage the disease and improve survival. There really are compounds out there that might be effective in manipulating gene expression in the brain.”
A correlation with the star-shaped cells in the brain and spinal cord called as astrocytes performing crucial functions is assumed. The disease generally revealed in infants is described with seizures, stunted motor skills and setbacks in cognitive development. The most visible exposure of the disease most often is the continuous enlargement of the head.
Messing, whose lab concentrates on the rare brain disease said, “We think the over-expression of GFAP is a big part of the picture. The protein aggregates affect a variety of pathways and we think there is a toxic threshold, so anything you can do to diminish production of the protein would be beneficial.”
An analysis was built up on the basis of the experiments conducted on mouse models. For determining the effects of 2880 drugs prevalent now on purified cultures of mouse astrocytes, the experts utilized advanced throughput screening. The expression of the gene was seemingly decreased from a range of 37 percent to 86 percent by ten drugs. Amongst the medications, clomipramine which is generally recommended in patients with obsessive-compulsive disorder was examined in mice for three weeks. The outcome was that approximately 50 percent compression of GFAP levels in the brain appeared.
Messing shared, “Without a biomarker, we’re not in a position to conduct a clinical trial. But I’m cautiously optimistic. I think we’re going to have more than one compound we can test.”
Though conclusions are drawn, Messing mentions that further research in animals models are required to ascertain the findings. Positive effects of the drugs in humans are yet to be determined in blood or spinal cord fluid markers. It will be conducted as an international collaborative research to identify such a marker.
The research is published online in the current, July 2010 issue of the journal Human Molecular Genetics.