Translational assessment of combined riluzole and minocycline in a pre-clinical model of rat spinal contusion injury
Funded in: 2016, 2017, 2018
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Problem: SCI activates a broad range of pathological mechanisms, thus an effective clinical therapy will likely involve a combination of interventions.
Target: Neuroprotective effects of a combination of two drugs
Goal: Assess the therapeutic efficacy of a combination of riluzole and minocycline
Despite years of research effort as well as a significant number of clinical trials, there remains no effective therapeutic intervention that will either preserve function following spinal cord injury (SCI). SCI activates a broad range of pathological mechanisms that contribute to chronic deficits such as motor dysfunction and neuropathic pain. We therefore believe it logical that an effective clinical therapy will likely involve not simply one therapeutic, but a combination of interventions, each of which targets a discreet range of pathological mechanisms.
Riluzole is a drug approved for the treatment of amyotrophic lateral sclerosis that recently was the target of a Phase I clinical trial for the acute treatment of SCI run by Dr. Robert Grossman, a co-Investigator on this study. Riluzole treatment was shown to be safe and to result in higher motor scores in patients with cervical spinal injuries. Riluzole suppresses neuronal sodium channels and reduces neurotoxicity following injury or in cases of CNS disease. Minocycline is an antibiotic shown to have potent anti-inflammatory properties in animal models of CNS disease and trauma. Minocycline demonstrated therapeutic potential in a recent Phase II clinical trial for the acute treatment of SCI.
Our goal in this study is to assess the therapeutic efficacy of a combination of riluzole and minocycline in order to target a broader range of pathological mechanisms than could be achieved with either drug delivered alone. We will determine whether this novel combination can both preserve motor function and prevent neuropathic pain in a clinically-relevant rodent model of SCI. This proposal brings together experts in pharmacokinetics, SCI modelling and human clinical trial design and implementation in order to optimize our ability to quickly translate our results into the clinic and improve function for those who have suffered an SCI.