19 - Clinical Trials in Rehabilitation With Neural Repair

Abstract

Media reports of successful experiments in brain- or spinal cord–injured rodents raise hope for imminent cures for paralysis, sensory loss, bladder dysfunction, neurogenic pain, and cognitive impairments. The translation from models of injury and repair to patient care, however, includes many potential confounders. Basic studies in developmental neurobiology and preclinical experiments in models of stroke, spinal cord injury (SCI), traumatic brain injury (TBI), multiple sclerosis, peripheral nerve injury, and other acute neurological diseases suggest the growing feasibility of strategies for neural repair to lessen the physical and cognitive impairments and disabilities in patients. Trials for these diseases differ from those for chronic degenerative diseases such as Alzheimer's and Parkinson's, which may aim to lessen symptoms and slow progression or stop the disease, as well as reverse impairments and disability, which is the main focus of regenerative strategies. Preclinical experiments that demonstrate neural repair must be interpreted with caution by clinicians who wish to apply studies of animal models of disease and regeneration to their patients. Preclinical data must reveal safety and identify the effects of the repair intervention on neural networks and on meaningful behaviors. Ideally, in vivo models bear parallels and recognizable differences from the cascades of post-injury and pro-restorative mechanisms that may evolve in patients. Experience-dependent learning may also drive neural and behavioral adaptations differently in caged rodents and people. With caution, biological experiments can lead to well-designed clinical trials to test new interventions.