In mice, loss of hindlimb motion due to spinal cord injury was significantly reversed by DNA encoding hyper-interleukin-6 (hIL-6), a designer cytokine. The DNA was delivered by an adeno-associated virus (AAV), which was injected just once, 30 min after spinal cord injury, into the sensorimotor cortex. This intervention promoted the regeneration of corticospinal and raphespinal fibers, improvements that led to locomotion improvements, as determined by tests using the Basso Mouse Scale and an automated catwalk gait analysis system. (excerpt)
Tag: growth factors
Abstract
Knockout of phosphatase and tensin homolog (PTEN−/−) is neuroprotective and promotes axon regeneration in mature neurons. Elevation of mTOR activity in injured neurons has been proposed as the primary underlying mechanism. Here we demonstrate that PTEN−/− also abrogates the inhibitory activity of GSK3 on collapsin response mediator protein 2 (CRMP2) in retinal ganglion cell (RGC) axons. Moreover, maintenance of GSK3 activity in Gsk3S/A knockin mice significantly compromised PTEN−/−-mediated optic nerve regeneration as well as the activity of CRMP2, and to a lesser extent, mTOR. These GSK3S/A mediated negative effects on regeneration were rescued by viral expression of constitutively active CRMP2T/A, despite decreased mTOR activation. Gsk3S/A knockin or CRMP2 inhibition also decreased PTEN−/− mediated neurite growth of RGCs in culture and disinhibition towards CNS myelin. Thus, the GSK3/CRMP2 pathway is essential for PTEN−/− mediated axon regeneration. These new mechanistic insights may help to find novel strategies to promote axon regeneration.
Researchers have developed a molecule that can restore lost connections in the spinal cords and brains of mice with cerebellar ataxia, Alzheimer’s disease and spinal cord injury.
Researchers have demonstrated that a molecule they created can restore lost connections in the spinal cords and brains of mice with neurological disorders including cerebellar ataxia, Alzheimer’s disease and spinal cord injury.
The research involved scientists in the UK Medical Research Council Laboratory of Molecular Biology (MRC LMB) and collaborators from Japan and Germany.
This scientific commentary refers to ‘Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury’, by Wang et al. (doi:10.1093/brain/awaa116).
Abstract
Spinal cord injury (SCI) possesses a significant health and economic burden worldwide. Traumatic SCI is a devastating condition that evolves through two successive stages. Throughout each of these stages, disturbances in ionic homeostasis, local oedema, ischaemia, focal haemorrhage, free radicals stress and inflammatory response were observed. Although there are no fully restorative cures available for SCI patients, various molecular, cellular and rehabilitative therapies, such as limiting local inflammation, preventing secondary cell death and enhancing the plasticity of local circuits in the spinal cord, were described. Current preclinical studies have showed that fibroblast growth factors (FGFs) alone or combination therapies utilizing cell transplantation and biomaterial scaffolds are proven effective for treating SCI in animal models. More importantly, some studies further demonstrated a paucity of clinical transfer usage to promote functional recovery of numerous patients with SCI. In this review, we focus on the therapeutic capacity and pitfalls of the FGF family and its clinical application for treating SCI, including the signalling component of the FGF pathway and the role in the central nervous system, the pathophysiology of SCI and the targets for FGF treatment. We also discuss the challenges and potential for the clinical translation of FGF‐based approaches into treatments for SCI.
In laboratory experiments, a chemical compound found in the shell of the cashew nut promotes the repair of myelin, a team from Vanderbilt University Medical Center reports today in the Proceedings of the National Academy of Sciences.
Scientists from the city have managed to regrow spinal nerves in rats after activating a molecule found in nerve cells by using their very own gel.
Dr Wenlong Huang, Dr Derryck Shewan and Dr Alba Guijarro-Belmar from Aberdeen University’s Institute of Medical Sciences found triggering a molecule called Epac2 led to “significant improvement” in the growth of nerves that been severed following injury.
A drug that repairs damage to the brain and spinal cord has been created by British scientists offering hope for new therapies that address a range of devastating conditions—from Alzheimer’s to epilepsy to paralysis.
Link – Clinical trial
Recruitment Status : Recruiting
First Posted : June 18, 2019
Last Update Posted : January 18, 2020