Valproic acid treatment reduced Aβ plaques (arrows) in the brains of mice with Alzheimer's-like disease.
Mice with the AD-like disease typically develop amyloid-rich brain plaques after six months. When Qing et al. treated the mice with valproic acid soon after plaque formation, the plaques shrank and some of the damaged axons in their brains resumed growth. The drug also improved performance in memory tests.
The acid worked by inhibiting the activity of glycogen synthase kinase-3β (GSK-3β), which normally turns on γ-secretase—the enzyme that cleaves β-amyloid precursor proteins. Lithium chloride, another drug used in patients with AD, also curbs amyloid-β production by inhibiting GSK-3α and GSK-3β, and has recently been shown to ameliorate axonal damage.
Valproic acid helped mice less as their disease progressed. The authors thus suggest that clinical trials should focus on people with early signs of AD. Valproic acid has been given to people with AD in the past but, unfortunately, memory improvement was never assessed in those studies. AM
