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Improving arm and hand function after stroke with clinically-relevant delivery of neurotrophin-3 to elderly disabled muscles: from rats to humans (StrokeTherapy)
Start date: Nov 1, 2012, End date: Oct 31, 2017 PROJECT  FINISHED 

Stroke disables millions worldwide and costs the EU €38 billion each year. Excitingly, my team has identified a clinically-feasible therapy for stroke which reverses disability in rats when given in a clinically-relevant time frame. Specifically, we have shown that the human growth factor neurotrophin 3 (NT3) promotes locomotor recovery and reverses sensory neglect in adult rats when infused into disabled arm muscles, starting 24 hours after stroke. Importantly, Phase II clinical trials have shown that systemic, repeated high doses of neurotrophin-3 are safe and well-tolerated in humans with other conditions. This paves the way for a Phase II trial in humans after stroke.We now wish to maximise arm and hand (paw) recovery in elderly rats with larger strokes by optimising dose, timing and route. We will then submit for approval a Clinical Trial Application for a randomised, double-blinded, placebo-controlled Phase II human clinical trial to treat stroke using NT3.We also propose multidisciplinary, cutting-edge studies to understand how NT3 promotes plasticity in the brain and spinal cord. 1) We will use wireless neural recording in awake rats and functional brain imaging to study plasticity after stroke and NT3 treatment. 2) Our innovative “RatBot” will automatically train, rehabilitate and assess grasping of pellet food. 3) To reveal where NT3 is transported we will track a novel tagged version of NT3 in vivo. 4) In an ambitious final study we will maximise recovery of arm and hand function in elderly rats when treatments are delayed by 1 month after larger strokes.In summary, we propose a high-risk, high-yield, transdisciplinary, innovative programme of work to maximise sensory and motor recovery after stroke in elderly rats. Treatment will be initiated in a clinically-relevant time frame (after 24 hours or 1 month) using a clinically-relevant dose and duration of treatment via a clinically-straightforward route, ready for a Phase II clinical trial.
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