How valproic acid works
It is not entirely understood how valproic acid reduces seizures. However, the medicine has been shown to inhibit GABA degradation. GABA is a neurotransmitter, a signaling molecule in the brain, that inhibits the activity of brain cells, or neurons.
Valproic acid may also block the reuptake of GABA, thereby increasing GABA levels in the brain. High GABA levels can help decrease the uncontrolled firing of neurons that cause seizures in Batten disease patients.
Valproic acid can also act as an ion channel modulator. Ions are small negatively or positively charged molecules. The transmission of electrical signals between neurons is mediated through the flow of ions through ion channels found on the surface of neurons.
Ion channel modulators reduce repetitive firing of neurons by prolonging the inactive state of the ion channel after activation.
Valproic acid in clinical trials
Valproic acid has not been tested in randomized clinical trials specifically for the treatment of Batten disease, but a small study suggests that Batten disease patients may benefit from this medication.
During the study, 27 patients received valproic acid, eight of them as a monotherapy. The remaining 19 patients received the medication in combination with other anticonvulsants. The mean dose of valproic acid monotherapy was 23.9 mg per kg a day.
After one year of valproic acid therapy, seizure frequency decreased by more than 50% in 81% of patients who received valproic acid either alone or in combination with other anticonvulsants.
Seizure control was defined as satisfactory if the patient had six or fewer seizures per year with a seizure duration of less than 20 minutes. With valproic acid monotherapy, a satisfactory seizure control was achieved in 70% of patients.
Four patients received valproic acid in combination with two other anticonvulsants, but seizure control was not satisfactory in these patients.
The study did not analyze whether the difference in response to valproic acid mono or combination therapy was statistically significant.
Common side effects of valproic acid use include nausea, vomiting, impaired vision, and weight loss or gain.
Valproic acid can cause hyperammonemic encephalopathy in Batten disease patients. Hyperammonemic encephalopathy is an alteration in brain structure or function that is caused by high ammonia levels in the blood. This risk is increased when valproic acid is used in high doses, in combination with other anticonvulsants or over a prolonged period.
Discontinuing valproic acid can reverse hyperammonemic encephalopathy. Low levels of carnitine in the blood, which is common in juvenile Batten disease patients, is another risk factor for hyperammonemic encephalopathy. Adding carnitine to valproic acid therapy may reverse the condition.
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