Nimodipine Treatment to Enable Motor Recovery After Paralyzing Spinal Cord Injury
Abstract
About 70% of people with spinal cord injury (SCI) experience spasticity and muscle paralysis. About half of those receive a pharmacological treatment to reduce spasticity and a rehabilitation therapy to recover functional movements. Since no curative treatment exists for spasticity and the usage of antispastic drug with neurorehabilitation worsens motor recovery, we propose to investigate the therapeutic action of an innovative antispastic treatment to enable neurorehabilitation in paralyzed SCI individuals. The treatment is based on nimodipine, an Food and Drug Administration-approved blocker of L-type calcium channels that prevents abnormal muscle activity after SCI even when the treatment is terminated. We hypothesize that, in contrast to current antispastic medications, nimodipine will lessen spasticity severity without interfering with recovery of motor function via neurorehabilitation strategies. First, we will investigate in a mouse model of thoracic injury the efficacy of the nimodipine treatment in preventing spasticity in comparison to the main antispastic drug, baclofen. Second, we will determine the effects of nimodipine treatment on spontaneous motor recovery. Finally, we will determine the effects of the treatment on neurorehabilitation-induced motor recovery when the training occurs with the treatment on when the treatment is interrupted. Spasticity will be assessed with clinical measurements such as responses to electric stimulation, muscle tone, and spasm occurrence while measuring locomotor performance on a motorized treadmill as a proxy for motor recovery. Spasticity not only represents a lifespan motor dysfunction, but even its occurrence and its pharmacological treatment represent major impediments to motor recovery. No antispastic medication currently allows long-term prevention of spasticity while also allowing for neurorehabilitation. The exploration of the nimodipine treatment on these crucial aspects of the SCI condition will identify the beneficial effects of the treatment, possible limitations, and therapeutic potentials with neurorehabilitation. The beneficial effects and the high translational potentials of the nimodipine treatment may represent a major advance for the management of the human SCI condition. From our recently published work and new unpublished results, new explorative clinical studies have begun to test nimodipine treatment on SCI patients. Furthermore, apart from people with SCI, a significant population of patients with stroke, multiple sclerosis and cerebral palsy receive antispastic medications. Preclinical investigation of the effects of the nimodipine treatment on motor recovery in SCI is a crucial aspect to investigate to further accelerate the translational process for the clinical application of the treatment for the treatment of the human SCI condition.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210297
Entities
People
- Carmelo Bellardita
Organizations
- United States Army
- University of Copenhagen