Tuesday July 28 2009
The rats turned blue for a week [Pic: Univ of Rochester]
The Times today reports that a blue food dye “may help cure spinal injuries but will turn patients blue”. The food dye, called Brilliant Blue G (BBG), is “similar to the one used in blue M&Ms and liquorice allsorts”.
Researchers report that they injected rats with BBG or water 15 minutes after they received a spinal injury. After 42 days none of the rats injected with water could walk, but the best-performing BBG rats were able to co-ordinate their front and back legs enough to support their weight and walk. A side effect of the treatment was that the rats’ skin turned blue for a week.
This animal study has identified some benefits of the dye BBG when injected shortly after spinal cord injury in rats. Although some of the BBG rats were able to make consistent weight-bearing steps, it is unclear exactly what proportion of the rats was able to do this. This potential treatment will require more animal research to determine its longer-term effectiveness and safety. In addition, determining whether BBG injections need to be given in the first 10 to 15 minutes after injury to have an effect is important, as this is unlikely to be feasible in many cases of human spinal injury. At present it is also unclear whether this treatment would be suitable for use in humans, or for which types of spinal injury.
Where did the story come from?
Dr Weiguo Peng and colleagues from University of Rochester Medical Center in New York carried out this research. The study was funded by the New York State Spinal Cord Injury program, the Miriam and Sheldon Adelson Medical Research Foundation and the National Institutes of Health in the US. The study was published in Proceedings of the National Academy of Sciences of the United States of America, a peer-reviewed scientific journal.
What kind of scientific study was this?
This was an animal study looking at the effects of the chemical Brilliant Blue G (BBG) on spinal cord injury. The researchers report that, apart from steroids, “no effective treatment is currently available to treat acute spinal cord injury [in humans]”. According to the researchers, steroids provide “at best modest protection to a subset of patients”.
A chemical called adenosine triphosphate (ATP) is released in large amounts following spinal injury, which causes the nerves in the spinal cord to fire signals excessively to surrounding cells. This ultimately leads to the death of the firing cells. ATP is thought to have this effect by acting on a protein called P2X7R, and the researchers had previously found that blocking this effect reduced the severity of spinal cord injury in animals.
However, in their previous experiments the researchers found that the chemical they used to block the action of ATP (OxATP) could not cross the blood–brain barrier, which is the barrier between the blood system and the fluid surrounding the brain and spinal cord. This means that the chemical would have to be injected directly into the spinal cord to reach the affected site. In addition, OxATP had adverse effects on the heart, so the researchers wanted to identify an alternative.
The chemical BBG was selected as an alternative because it has similar chemical properties to OxATP, can cross the blood–brain barrier and has low toxic effects. BBG is derived from a blue food dye called FD&C blue No. 1, which had been shown to be safe in healthy animals and is approved for use in foodstuffs.
The researchers took albino rats that had received spinal crush injuries to the spinal cord, which had been surgically exposed. The mice were intravenously injected with a BBG solution or a control fluid, which was the same fluid that was used to dilute the BBG but with no BBG added. The rats received two different concentrations of BBG, equivalent to either 10 or 50mg per kilogramme of bodyweight. The injections were given 10-15 minutes after the injury and once each day for the next two days.
The researchers monitored the rats over a six-week period, looking at whether they recovered any movement. They also looked at what was happening within the damaged regions of the spine using a microscope.
What were the results of the study?
The BBG injections did not appear to have any effect on the rats’ behaviour, weight, survival or measures such as temperature or blood pressure. However, both doses caused the rats’ eyes (which are normally pink) to turn blue, and the higher dose turned the rats’ skin blue. This skin colouration was temporary, the skin returning to normal over the course of a week.
The researchers found that rats that had received BBG injections showed “modest improvements” in ability to move as early as two to three days after the injury, measured using a standard scale. Their ability to move improved “relatively rapidly” over the first 13 days and then slowed down. The rats treated with BBG improved faster than the control rats. Those BBG-treated rats that made the greatest recovery showed co-ordination of their front and back legs, and could make consistent steps and support their weight by day 42. None of the control rats showed co-ordination of their front and back legs, and they could only occasionally make steps that supported their weight at this stage.
At day 42 the rats injected with BBG showed less tissue loss at the site of the injury than control rats. The BBG-injected rats also showed lower levels of inflammation compared to the control rats. The rats that received the higher dose had more BBG at their injury site than those that received the lower dose of BBG.
What interpretations did the researchers draw from these results?
The researchers conclude that intravenous administration of BBG “significantly reduced the severity of spinal cord damage without any evident toxicity”. They suggest that although they used BBG by itself, if it were combined with other treatments it “may well enhance the possibility of optimal recovery of function following traumatic injury to the human spinal cord”.
What does the NHS Knowledge Service make of this study?
This animal study has identified some benefits of the dye BBG when injected shortly after spinal cord injury in rats. Although some of the BBG rats were able to make consistent weight-bearing steps, it was unclear exactly what proportion of the rats was able to do this.
While any research into potential treatments for spinal cord injuries is of great interest, more research into BBG is required. This would initially require further animal research to determine the long-term effectiveness and safety of BBG, both by itself and in combination with other treatments.
It is unclear at present whether this treatment would be suitable for use in humans, or for which types of spinal injury. In addition, a scenario such as this, where BBG injections might need to be given in the first 10 to 15 minutes after injury, is highly unlikely to be feasible in the emergency circumstances surrounding many cases of human spinal injury.
The Daily Mail has also reported on this study, with the headline that the blue M&M sweet could be “a magic pill for spinal injuries”. This is not representative of the research. It should be noted that M&Ms were not tested in the study, the blue dye used in this experiment was not the same as the blue food dye and the dye was injected intravenously rather than being ingested in either pill or sweet form.