Systemic Administration of Endogenous Stem Cell Activator

Frankfurt, Germany -

Valproic acid is a histone deacetylase inhibitor which is clinically used for the treatment of bipolar disorders and epilepsy. Valproic acid has been demonstrated to increase proliferation and expansion of CD34 stem cells in vitro. Additionally, valproic acid has demonstrated positive effects at reducing pathological post infarct cardiac remodelling, as well as possessing ability to benefit muscular dystrophy.

In a recent study (Atmaca et al. Valproic acid (VPA) in patients with refractory advanced cancer: a dose escalating phase I clinical trial.Br J Cancer. 2007 Jun 19) valproic acid was administered to cancer patients.

Treatment refractory advanced cancer patients (26 in total) were randomized into groups of 3 and given escalating doses of intravenous valproic acid starting at 30 mg/kg/day for 5 days on 2 days off as part of a 21 day cycle.

Maximum tolerated dose achieved was 60 mg/kg/day. The adverse effects seen were grade 3-4 neurological side effects (8/26 patients). No severe hematological adverse effects were seen.

Hyperacetylation of peripheral blood mononuclear cells was observed as well as suppression of HDAC2. Serum average concentrations of >120 and maximal concentrations > 250 mg/liter were achieved in the patients in the higher dose ranges (The 90 and 120 mg/kg dose cohorts).

In conclusion, this study provides some examples of higher serum concentrations of valproic acid than can be obtained with the traditional oral administration of valproic acid. This study is a useful basis for future studies using pharmacological administration of valproic acid to enhance stem cell activity.

The study should be examined for increases in blood cell production since other papers have described that valproic acid at these concentrations stimulates hematopoiesis.