The Specific Requirements of Neural Repair Trials for Stroke

Abstract

Novel molecular, cellular, and pharmacological therapies to stimulate repair of sensorimotor circuits after stroke are entering clinical trials. Compared with acute neuroprotection and thrombolysis studies, clinical trials for repair in subacute and chronic hemiplegic participants have a different time course for delivery of an intervention, different mechanisms of action within the milieu of the injury, distinct relationships to the amount of physical activity and skills practice of participants, and need to include more refined outcome measures. This review examines the biological interaction of targeted rehabilitation with neural repair strategies to optimize outcomes. We suggest practical guidelines for the incorporation of inexpensive skills training and exercise at home. In addition, we describe some novel outcome measurement tools, including wearable sensors, to obtain the more detailed outcomes that may identify at least some minimal level of success from cellular and regeneration interventions. Thus, proceeding in the shadow of acute stroke trial designs may unnecessarily limit the mechanisms of action of new repair strategies, reduce their impact on participants, and risk missing important behavioral outcomes.

Keywords: axonal sprouting; clinical trials; mHealth; brain tissue regeneration; neuronal plasticity; physical therapy; stem cell; stroke rehabilitation.

Figure

Progression of stroke damage, tissue reorganization and behavioral gains in the normal condition and after a neural repair therapy. The top panel (A) shows the progression from initial cell death through secondary damage and then the limited repair and recovery after stroke. The bottom panel (B) shows the goals of a neural repair therapeutic, in which endogenous neuroplasticity is enhanced and extended in time, leading to a higher level and more prolonged recovery of neurological impairments.