Right combination results in improvements


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Intense training is the most clinical successful treatment following spinal cord injuries. Scientist also know: Nogo-A is a protein that inhibits the natural regeneration of neurons after a spinal cord injury and blocking it (by using an antibody) will result in a robust functional regeneration. With this in mind, a project team aimed at understanding the exact effect of sequentially combining the suppression of Nogo-A with a delayed and intense walking training.

Effects of sequential therapy
Previous findings demonstrate that intense training is not only having beneficial effect but can interfere with other interventions. The main focus of this project was therefore to understand if the sequential treatment could harness both positive effects without losing any of the single “potency”. Scientists were pleased to find that while intense training and suppression of Nogo-A are both improving the functional recovery after a spinal cord injury, the sequential treatment results in a cumulative effect. Accurate anatomical and functional testing confirmed that both positive effects took place one on top of the other without interfering.

The fewer the better
The team also made an unexpected observation.While the treatment alone increased the amount of connectivity (sprouting and synapse formation), when the treatment was followed by the intense training the overall number of connections diminished. From this observation, they concluded that this mimicked a mechanism that takes place during embryonic development: the reinforcement of functionally important fibers and pruning of over-zealous fibers, that in spinal cord injury could potentially induce spasticity.

 

Next steps
The sequential timeline for different interventions reflects in some way the current standard of care of spinal cord injured patients. It is therefore safe to conclude that clinicians will include these positive observations within clinical trials, in particular in the soon starting clinical trial testing the efficacy of an anti-Nogo treatment that enroll up to 52 subjects.

 

Source: “Sequential therapy of anti-Nogo-A antibody treatment and treadmill training leads to cumulative improvements after spinal cord injury in rats”. Chen K, Marsh BC, Cowan M, Al'Joboori YD, Gigout S, Smith CC, Messenger N, Gamper N, Schwab ME, Ichiyama RM. Experimental Neurology, April, 2017.