Phase I Trial of Valproic Acid in Healthy Volunteers / Trauma Patients
Abstract
Phase I Trial of Valproic Acid in Healthy Volunteers / Trauma PatientsHemorrhage is the leading cause of preventable trauma deaths. About 50% of trauma patients with a systolic blood pressure less than 90 mmHg die in spite of current treatment. The highest mortality occurs within the first hour after injury, underlying the need for a therapy that is safe, efficacious, widely available, and can be used under emergent circumstances. Valproic acid (VPA), a histone deacetylase inhibitor, holds exciting promise as such a drug.The performer has shown that VPA when given at a single high dose (300mg/kg) by intravenous administration was able to prolong survival in pre-clinical rodent and swine poly-trauma models. The underlying protective mechanisms have been well-characterized, and increased short-term survival correlates with changes in global gene regulation caused by histone deacetylase inhibition, as well as prompt activation of many pro-survival proteins. Thus, treatment with VPA produces protective effects at the cellular and molecular level which translates to functional preservation of organs and organ systems under conditions of extreme blood loss.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 23, 2016
- Source ID
- N000141613135
Entities
People
- Hasan B Alam
Organizations
- Board of Regents of the University of Michigan
- Office of Naval Research
- United States Navy