Effects on Locomotion, Muscle, Bone, and Blood Induced by a Combination Therapy Eliciting Weight-Bearing Stepping in Nonassisted Spinal Cord–Transected Mice

Abstract

Although translation of these findings needs further experimentation, similar pharmacological activation of the CPG offers a novel therapeutic target to provide some health benefits in motor-complete SCI patients.

Cardiovascular disease and cancer associated with neurological problems: Some hope for innovative combinatorial approaches

“…Physical activity has been shown to prevent and mitigate cardiotoxicity related to anthracycline therapy whereas a lack of physical activity due to paralysis after SCI increases the prevalence of chronic comorbid diseases including cancer [12,13]. In other words, therapeutic approaches aimed at restoring or improving regular metabolically-challenging physical activity in patients with SCI shall contribute to reduce the incidence or severity of chronic diseases including CVD and cancer [13,14]. Recent evidence suggests that a drug candidate called Spinalon may be capable of eliciting spinal locomotor neuron activity and, hence, corresponding episodes of involuntary walking on a treadmill in completely paralyzed mice and humans [14,15].…”

“…In other words, therapeutic approaches aimed at restoring or improving regular metabolically-challenging physical activity in patients with SCI shall contribute to reduce the incidence or severity of chronic diseases including CVD and cancer [13,14]. Recent evidence suggests that a drug candidate called Spinalon may be capable of eliciting spinal locomotor neuron activity and, hence, corresponding episodes of involuntary walking on a treadmill in completely paralyzed mice and humans [14,15]. Transdermal electric stimulation has also recently been found to elicit on-demand locomotor-like movements in humans [16].…”

Adaptations of the Motor System in Animal Models of Spinal Cord Injury and Disuse

“…It has been determined that a tri-therapy composed of L-DOPA, carbidopa and buspirone is safe and ideally suited for further development at the clinical level (i.e., each drug is already FDA approved for diseases other than SCI and no abnormal pharmacology or toxicology data was found) as a first-in-class CPG activating drug treatment candidate. However, although efficacy in early chronic SCI mice has recently been demonstrated Guertin et al 2011), it remains unclear how repeated administration over several weeks would affect disuse-related motor system changes. As mentioned earlier, chronic SCI patients (especially motor-complete also called ASIA-A or ASIA-B patients) experience often life-threatening health problems also referred to as www.intechopen.com 'secondary complications' including motor system changes reported here also in this paraplegic mouse model.…”

Two Promising Novel Classes of Drug Treatment in Clinical Development for Acute and Chronic Spinal Cord Injury

“…In fact, we have been the first group to have recently developed a model of chronic SCI in which systemic and metabolic problems were thoroughly characterized [22]. In parallel to these experiments, we also identified and developed a drug product aimed to prevent several of these chronic problems after SCI by activating pharmacologically a spinal locomotor network based in the lumbar area of the spinal cord [23][24][25]. This is the first and still the only drug treatment candidate in development for chronic SCIrelated health problems.…”