We subjected rats to either partial mid-cervical or complete upper thoracic spinal cord transections and examined whether combinatorial treatments support motor axonal regeneration into and beyond the lesion. Subjects received cAMP injections into brainstem reticular motor neurons to stimulate their endogenous growth state, bone marrow stromal cell grafts in lesion sites to provide permissive matrices for axonal growth, and brain-derived neurotrophic factor (BDNF) gradients beyond the lesion to stimulate distal growth of motor axons. Findings were compared to several control groups. Combinatorial treatment generated motor axon regeneration beyond both C5 hemisection and complete transection sites. Yet despite formation of synapses with neurons below the lesion, motor outcomes worsened after partial cervical lesions and spasticity worsened after complete transection. These findings highlight the complexity of spinal cord repair, and the need for additional control and shaping of axonal regeneration.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. It is a rapidly advancing neurodegenerative disease leading to progressive paralysis and death, with a mean time of survival from onset of symptoms to death of 2-5 years. The pathophysiology of ALS remains poorly understood. The only US Food and Drug Administration-approved therapy for ALS is riluzole, a glutamatergic neurotransmission inhibitor, with modest benefits on survival. Many other agents have shown promising results in preclinical trials, but have yet to show benefit in human clinical trials. This review gives an overview of drugs that have been studied in clinical trials and their reported outcomes. This also includes more recent treatment strategies, including antisense oligonucleotides (ASOs) and stem cells. ASOs have the potential to target genes known to cause ALS by silencing their function. Many clinical trials are under way using these therapies. Different kinds of stem cells have been used in an attempt to either replace the lost motor neurons or to improve their metabolic supply and thus prolong their death. Given the limited therapeutic treatment options to date, the most important approach to improve the patient's quality of life remains symptom-based management. Additionally, we give an overview of the current treatment offered in multidisciplinary clinics.