 Preclinical Assessment of Progesterone Treatment for Pediatric Traumatic Brain InjuryDonald Stein, PhD
Small Project PI |
| Who: |
End users: Acute pediatric traumatic brain injury (TBI) population
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| What: |
The goal is to provide the requisite pre-clinical data for a pilot clinical study of the safety and efficacy of progesterone (PROG) treatment in acutely brain-injured children. It is essential to conduct preclinical research because the injury mechanisms, pathology, physiology and functional outcomes associated with pediatric TBI may not be the same as those in adults. To account for any possible sex differences in outcomes, we will conduct experiments using both male and female animals. Three proposed aims are: (1) using a controlled cortical impact (CCI) model of injury, determine the effects of PROG on post-injury development and resolution of necrotic lesion and functional deficits in juvenile male rats, and determine the dose most clearly associated with benefit; (2) using the best dose identified in male rats, determine the effects of PROG on the post-injury development and resolution of necrotic lesion and functional deficits induced by CCI injury in juvenile female rats; and (3) determine both optimal and acceptable therapeutic windows for administering PROG following CCI injury in juvenile rats.
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| Why: |
TBI is an important cause of death and disability in adults and children worldwide and in the United States. Of the 1.2 million TBIs in the U.S. each year, 400,000 involve children. Each year, about 3,000 children between 0 and 18 years die, 29,000 require hospitalization, and 400,000 are treated in emergency rooms due to TBI. Other than hypothermia, which remains investigational, there are no effective treatments for TBI. A safe and effective early intervention to limit damage and improve behavioral outcomes after TBI would materially advance CDC injury control objectives. A large and growing series of preclinical studies and two human clinical trials have found that PROG has neuroprotective effects in acutely brain-injured adults. PROG has a long track record of safe use in other medical conditions. It is easy to administer, it is inexpensive, and it has demonstrated proof of principle for safety and efficacy in preclinical and clinical trials. However, it is not known whether PROG treatment will be as safe and have the same beneficial effects in acutely brain-injured children. It is important to examine the potential risks and benefits of PROG treatment in pediatric animal models of TBI before testing it in children. |
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| Impact: |
The current proposal specifically advances this mission by studying an effective acute-phase treatment for pediatric TBI. Given the lack of alternatives for treating TBI in children, and promising findings from two separate clinical trials in adults, the preclinical data generated will help advance the agenda to assess the safety and feasibility of conducting a clinical trial with PROG in children. |
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| Return on Investment: |
Potentially huge saving in life, quality of life and in expenses associated with long-term care and rehabilitation. |