“Renewed hope for patients paralysed by spine injuries,” The Independent reports.
This hope is due to the possibility of developing a new drug based on a molecule called intracellular sigma peptide. The drug helped restore varying degrees of nerve functions in rats that had spinal cord injuries.
The spinal cord is a cable of nerve cells that transmits signals from the brain to the rest of the body. Damage to the spinal cord can result in paralysis; the higher up the injury occurs, the greater the degree of paralysis.
In this study, researchers identified some of the processes that create a barrier to nerves being able to sprout out through the nerve scar tissue. This sprouting could potentially repair the injury. They then developed a drug that could cause a disruption to this barrier.
Rats with a spinal cord injury were given a daily injection of the drug for seven weeks, 11 weeks after the injury, 21 out of 26 rats had regained some function in their bladder and/or hind legs.
Further tests will be conducted to see if the drug can be made more effective. Longer-term tests will be required to look for any side effects before any human studies can be performed.
Where did the story come from?
The study was carried out by researchers from Case Western Reserve University in Ohio, Ohio State University, the University of Manitoba in Canada and other US institutes. It was funded by the National Institute of Neurological Disorders and Stroke, the Case Western Reserve University Council to Advance Human Health, Unite to Fight Paralysis, the Brumagin Memorial Fund, Spinal Cord Injury Sucks, United Paralysis Foundation and the Kaneko Family Fund.
The study was published in the peer-reviewed journal Nature.
The research was accurately reported by the UK media. However, some of the headlines were a little premature, as the novel drug needs to undergo a significant amount of animal testing before it could progress to any human trials.
What kind of research was this?
This was an animal study, which aimed to test a new approach to nerve regrowth after a spinal injury.
Normally, part of the scar tissue that is formed around the nerves creates a barrier, preventing nerve regrowth. Recent research identified a protein that can inhibit too much of this scar tissue from forming.
What did the research involve?
The research involved several laboratory experiments, using nerves from rats and mice to determine the function of several proteins involved in nerve regeneration. This increased the researchers’ understanding of which proteins were stimulating unhelpful growth of certain nerve cells that were stopping normal growth.
The researchers then developed a molecule called intracellular sigma peptide (ISP) that could bind to a receptor to stop the unwanted growth. A second molecule called LAR wedge-domain peptide (ILP) was also identified, which naturally bound to the receptor, but less strongly.
Using the results of these tests, the researchers moved on to an animal experiment. Rats had a spinal cord injury inflicted on them (a “dorsal column crush”), which caused damage between the nerves of the bladder and the brainstem. This prevented them from being able to urinate very often, causing an increased volume of urine to collect in the bladder.
The injury also prevented them from moving their hind legs.
The day after the spinal cord injury was inflicted, rats were given a daily subcutaneous injection (just under the skin of the back, just above the level of the injury) for seven weeks, of either:
- placebo (a dummy treatment)
The researchers compared the three groups of rats 12 weeks after injury to determine nerve regrowth in terms of:
- the frequency of urination and amount of fluid in the bladder
- the ability to move their hind legs
What were the basic results?
Some form of functional recovery was seen in 21 out of the 26 rats treated with ISP.
Rats given ISP were able to urinate twice as frequently as rats given the placebo. They also had significantly less urine accumulating in the bladder.
Of the rats treated with ISP, 10 out of 15 had developed some bladder muscle co-ordination compared to none of the rats treated with ILP or placebo. This indicated a degree of normal nerve regrowth and connections.
30% of the ISP-treated rats were able to walk with “coordinated stepping” using their hind legs by week 11. There was also some recovery of coordination and balance. The rats given ILP or placebo were only able to do occasional weight bearing by this time.
The researchers report that the ISP-treated rats did not experience neuropathic pain (pain from the damaged nerves).
How did the researchers interpret the results?
The researchers concluded that “Systemic modulation of PTPσ [the receptor] opens a new therapeutic avenue in non-invasive treatments for enhancing functional recovery after a variety of injuries or diseases in which proteoglycans inhibit the attempt of axons [nerve cell fibres] to regenerate or sprout.”
In other words, the injection of ISP can improve normal regrowth of the nerves at the site of injury in rats.
This exciting piece of research has found that the immediate treatment of spinal cord injuries using a newly-developed molecule can improve nerve regeneration, leading to some functional recovery in rats. The drug appears to work by disrupting the unhealthy pattern of scar tissue that develops and usually stops nerves from growing and lengthening, instead forming tight knots.
The tests performed on rats appear to show that injections of the drug following a spinal cord injury led to improved bladder function, walking ability and balance.
The researchers report that the rats did not develop neuropathic pain, which often happens when damaged nerves do not grow back normally. They also did not report any side effects with the treatment, aside from some inflammation at the injection site. When the research gets to the point of human trials, the accuracy of these observations will be much easier to determine, but this is a long way off.
Further tests will now be conducted to see why the drug did not work for five of the rats and to determine the optimal dose. Longer-term tests will also be required to look for any side effects that may occur with this treatment before any human studies can be performed.