Lancet neurology
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The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics. ⋯ Approaches using membrane transporters and receptor-mediated transcytosis are less invasive than are other techniques, but they can have off-target effects. Nanotherapeutics have shown promise, but these strategies are in early stages of development. Advancements in drug delivery across the blood-brain barrier will require appropriately designed and powered clinical studies, with a focus on the timing of treatment, demographic and genetic considerations, head-to-head comparison with other treatment strategies (rather than a placebo), and relevant primary and secondary outcome measures.
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Randomized Controlled Trial Multicenter Study
Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: a randomised, double-blind, multicentre, placebo-controlled, phase 2b trial.
Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury. ⋯ EU program Horizon2020; Swiss State Secretariat for Education, Research and Innovation; Wings for Life; the Swiss Paraplegic Foundation; and the CeNeReg project of Wyss Zurich (University of Zurich and Eidgenössische Technische Hochschule Zurich).