Photosensitivity as a Preclinical Assessment for Treatment of Post-Traumatic Headache
Abstract
The proposed research addresses Neurosensory and Rehabilitation Research Award Focus Area "Vision Dysfunction," as well as "Pain Management." The overall objective will be to use photosensitivity as a way to measure post-traumatic headache and to thereby improve the diagnosis and development of treatment strategies. Unfortunately, headache with associated photosensitivity is prevalent in both active-duty personnel and Veterans who have suffered traumatic brain injury (TBI). The high incidence of these often debilitating symptoms underscores the need to study these problems in animals in order to develop new and effective treatments for post-TBI headaches. We hypothesize that modeling TBI in mice will cause migraine-like photosensitivity and that treatment with two classes of promising pharmacological agents will reduce this photosensitivity. Members of the first class inhibit a small protein, the calcitonin gene-related peptide (CGRP), which has been firmly established to play a key role in migraine. Both antagonists of the CGRP receptor and antibodies that can block the activity of CGRP -- which have proven effective in migraine clinical trials as acute and preventative treatments, respectively -- will be tested. The apparent low toxicity of the CGRP antibodies is especially encouraging for treating chronic post-TBI headaches. The second class of agents to be tested is represented by a neuroprotective compound, P7C3-S243, that was developed by our laboratory. This agent is currently enrolled in the Investigational New Drug program as a class of neuroprotective agents that show great promise in multiple preclinical models of neurodegeneration, including TBI-associated cognitive, motor, and visual symptoms; amyotrophic lateral sclerosis; peripheral nerve degeneration; aging-associated cognitive decline; and Parkinson s disease. In summary, we propose to test the preclinical efficacy of two promising new therapeutics that act by different mechanisms. Specifically, P7C3-S243 boosts the production of a key energy metabolite in cells, whereas the CGRP-directed agents most likely act by reducing neural activity in pain pathways. Our preliminary data support the testing of these promising agents for efficacy in the prevention and treatment of post-TBI migraine headache and photosensitivity. Furthermore, the proposed experiments will leave us perfectly poised to study of combination therapy with these agents, which might have a synergistic therapeutic effect. Collectively, our work will provide a foundation for developing new ways to prevent and improve the treatment of military personnel with post-traumatic migraine-like headaches and photosensitivity.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1610071
Entities
People
- Andrew F Russo
Organizations
- United States Army
- University of Iowa