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Regenerative Medicine Musculoskeletal Respiratory

One Time Injection Restores Function After Spinal Cord Injury

2 weeks, 1 day ago

1943  4
Posted on Nov 28, 2018, 4 p.m.

Approximately 250-500,000 spinal cord injuries occur worldwide every year, severe cases result in partial or complete paralysis, over half of SCIs the patients will have breathing problems because the diaphragm is affected, as published in Nature Communications.

Scientist from the USA and UK have demonstrated that long term diaphragm function and partial limb function can be restored in rats with chronic SCI following a single injection of chondroitinase ABC enzymes; it is hoped this treatment will also work to restore motor functions to human SCI patients.

Both breathing and some arm function in a form of high cervical, chronic spinal cord injury induced paralysis has been permanently restored for the first time; complete recovery especially of breathing occurs rapidly after long term paralysis in rodent models.

Prior studies have suggested some level of respiratory muscle activity can be restored by treatment with ChABC administered soon after cervical hemisection. Enzymes break down a type of proteoglycan that inhibits new axonal growth, however these only result in about 10% recovery of respiratory muscle activity.

This study involved rats with SCI having severed spinal cords at cervical vertebra C2, that were given a single injectection of ChABC which was administered 3 months after injury at the site of injury. A week after treatment new nerves started to grow and restore diaphragm function on the damaged side in 60% of the animals; within 2 weeks all animals treated demonstrated improvements despite having been paralyzed most of their lives. The techniques appeared to work better at chronic stages rather than at acute stages.

Animals were able to walk, feed, and drink normally with problems using their forelimbs on the damaged side. 70% of the animals were better able to use those limbs within a week of treatment compared to 30% of controls.

SCI animals with intermittent hypoxia appeared to have the best benefits, when ChABC was combined with IH diaphragm activity increased to 40%, application ChABC with or without IH resulted in restoration of synchronized diaphragm function ipsilateral to the injury in 66.7% of the animals; combination treatment promoted coordinated motor activity indistinguishable from normal respiration.

The correct balance of IH therapy is crucial, too much results in abnormal electrical activity in the diaphragm, which may be why the body releases inhibitory molecule to prevent restoration of functional axons in the spinal cord. Treatment is being worked on to optimize recovery, particularly in the forearm.

Improvements were still evident in the animals 1.5 years after having the therapy of a single injection, in this first illustration of persistent and complete functional restoration in any motor system being possible after long term SCIs. The treatment is relevant to multiple types of chronic incomplete spinal traumas, which will hopefully help to restore motor function in humans following spinal cord injury.

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