First described in medical literature in 1949, Alexander disease is an extremely rare neurological disorder and form of leukodystrophy. Despite nearly 74 years having passed since its discovery, there is still much we don’t know about this condition. More research into Alexander disease and potential treatments (as no cures or targeted treatments exist) is needed. Because this disease is usually fatal, finding effective treatments could prolong life and has the potential to greatly improve outcomes.
In April 2023, the Worcester Business Journal reported that End AxD, a foundation committed to improving the lives of people with Alexander disease, granted $74,000 to Professors Jun Xie and Guangping Gao from the UMass Chan Medical School. With this funding, the professors plan to continue developing a potential gene therapy solution for this disease. Xie and Gao have already been developing a vector that silences the disease-causing variant in mice models. As they move forward with clinical development, the pair hopes to create a more advanced animal model of Alexander disease – and eventually get to the point where their therapy could be evaluated in human studies.
What is Alexander Disease?
An estimated 500 people worldwide are known to have Alexander disease. As described above, Alexander disease is considered a leukodystrophy. This particular disease is characterized by Rosenthal fibers (abnormal proteins) deposits and myelin sheath damage. Normally, the myelin sheath protects nerve fibers from damage or degeneration. In most cases, GFAP mutations are the cause, but the cause is unknown in around 10% of people.
There are four subtypes of Alexander disease based on the age of presentation: neonatal, infantile (beginning within 2 years of birth), juvenile (between ages 2-13), and adult (13+). The infantile form is the most common and the neonatal form is the most severe. Potential symptoms may, but do not always, include:
- Intellectual disability
- Mild-to-severe motor disability
- Hydrocephalus (“water on the brain”)
- Delayed physical development
- Dysphagia (difficulty swallowing)
- Poor coordination
- Enlarged head and brain
- Stiffness and/or paralysis of the arms and legs
- Excessive nausea and vomiting
- Failure to thrive
- Developmental delays