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Alexander disease is a progressive and rare neurological disorder with no cure or standard course of treatment. But a new study led by researchers at the University of Wisconsin–Madison involving a rat model of the disease offers a potential treatment for the typically fatal condition.
Alexander disease (AxD) is a rare neurodegenerative disorder that is caused by dominant mutations in the gene encoding glial fibrillary acidic protein (GFAP), an intermediate filament that is primarily expressed by astrocytes. In AxD, mutant GFAP in combination with increased GFAP expression result in astrocyte dysfunction and the accumulation of Rosenthal fibers.
Alexander disease results from gain of function mutations in the gene encoding glial fibrillary acidic protein (GFAP). At least eight GFAP isoforms have been described, however, the predominant alpha isoform accounts for approximately 90% of GFAP protein.
Glial cells have increasingly been implicated as active participants in the pathogenesis of neurological diseases, but critical pathways and mechanisms controlling glial function and secondary non-cell autonomous neuronal injury remain incompletely defined.
In a study published today, Waisman Center investigators Su-Chun Zhang, Albee Messing and colleagues point to new understandings of the broad range of effects that result from the GFAP mutation impacting astrocytes — important supporting cells which comprise 20 to 40 percent of all cells in the brain. Cells donated by patients with Alexander disease …
A single injection of antisense oligonucleotides into the lateral ventricle of adult mice leads to nearly complete elimination of GFAP throughout the CNS (GFAP quantitation by ELISA).
After more than a decade of work, researchers at the University of Wisconsin–Madison’s Waisman Center reported promising results in the lab and in animal models that could set the stage for developing a treatment for Alexander disease, a rare and usually fatal neurological disease with no known cure.
Alexander disease patient astrocytes have impaired calcium wave propagation Legend: A) Still images over time from mechanical stimulation of 6-month astrocytes loaded with Fluor-4AM and accompanying post-experiment GFAP stains. B) Average duration of increased calcium signal above threshold ± S.D. C) Average proportion of field of view traveled by calcium wave. D) Rate of calcium …
Waisman Center Director, Albee Messing, is collaborating with researchers at the Children’s Hospital of Philadelphia to better understand the progression of Alexander disease, a rare and fatal neurological disorder with no known cure. In a news story in the Belleville News-Democrat, Messing said that the study has already led scientists to several breakthroughs in …
Waisman Center Director, Albee Messing, VMD, PhD, was recently featured in the Know Your Madisonian column by David Wahlberg in the Wisconsin State Journal. To read the full interview, please click here. David Wahlberg, Wisconsin State Journal
