Alexander disease is a progressive and rare neurological disorder with no cure or standard course of treatment. But a new study involving a rat model of the disease offers a potential treatment for the typically fatal condition.
It’s a significant step in efforts to help people with the disease, says UW-Madison Waisman Center senior scientist Tracy Hagemann, who led the study alongside Albee Messing, professor emeritus of comparative biosciences and founder of the Alexander Disease Lab. With University of Alabama at Birmingham colleague Michael Brenner, Messing discovered the gene responsible for Alexander disease more than 20 years ago.
People born with Alexander disease may develop an enlarged brain and head, experience seizures or delayed development, have stiffness in their arms and legs, and have intellectual disabilities. The disease, which involves destruction of the white matter of the brain, is often not diagnosed until symptoms are pronounced, says Hagemann.
The new study, published Nov. 17 in Science Translational Medicine, provided preliminary data instrumental for a human clinical trial currently being led by Ionis Pharmaceuticals. Hagemann, Messing, and the Alexander Disease Lab are not directly involved.
However, working with Ionis Pharmaceuticals, the researchers developed a treatment that consists of small pieces of DNA called antisense oligonucleotides, which in their rat model was able to target mRNA in cells and tag the mRNA for destruction, effectively halting it from creating proteins.
One feature of Alexander disease is the formation of abnormal protein aggregates called Rosenthal fibers, caused by mutations in the gene that makes a protein called GFAP. The connection between this abnormal GFAP and the white matter destruction seen in Alexander disease is not yet clear, but changes in the protein are an intrinsic part of the disease in almost all cases.
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Materials provided by University of Wisconsin-Madison. Original written by Emily LeClerc. Note: Content may be edited for style and length.