Randomized placebo-controlled trial of valproic acid in patients with PSP
Lead Researcher Dr Pascal Derkinderen
Co-researchers Drs Philippe Damier, Franck Durif, Bérengère De Billy, Jean-Luc Houeto, Marc Vérin, Alexandre Kreisler, Luc Defebvre
Institution CHU Nantes, France
Duration 4 years.
Start October 2006. End of patient inclusion July 2008; last patient follow-up July 2010
Grant £13,000
Aim of research
To determine if sodium valproate can slow the progression of PSP.
About the research
Tau is a microtubule-associated protein that is abundant in the central nervous system where it is predominantly expressed in axons (the parts of the nerve cell that take impulses away from it). Apart from its physiological role, tau is also the main component of paired helical filaments (PHF) which are aggregated structures found in the brains of patients with a number of diseases called ‘tauopathies' including progressive supranuclear palsy (PSP).
When aggregated, tau is hyperphosphorylated (contains more phosphorus than usual) at specific sites. Tau hyperphosphorylation hinders its ability to bind to microtubules and it is therefore hypothesized that this hyperphosphorylation contributes to neurodegeneration through the destabilization of microtubules. Several enzymes have been identified that can phosphorylate tau. Among them, Glycogen synthase kinase-3 (GSK-3) has been proposed as the main enzyme able to aberrantly phosphorylate tau in tauopathies, raising the possibility of designing novel therapeutic interventions for these disorders based on GSK-3 inhibition.
Sodium valproate, a medication for seizure and bipolar disorders is a known inhibitor of GSK3 and has been reported to be neuroprotective both in vitro and in vivo. Therefore, it is of great importance to test the possible protective effects of sodium valproate in PSP patients.
Findings
Research is currently ongoing. Results will be updated annually or sooner if there is exciting news.
As a first result, the researchers have found that sodium valproate seems to be well tolerated in patients with PSP.
What will the outcome of this research mean for people with PSP?
From the results of this research it should be possible to determine if sodium valproate acts to slow the progression of PSP. Depending on the outcome of the work, sodium valproate may be of use in the treatment for PSP. This is particularly important as at present there is no effective treatment for PSP.