Molecule cocktail raises spinal injury hope

● Mixture could restore movement for people and aid recovery, say scientists

A chemical “cocktail” could restore movement for people crippled after suffering spinal cord injuries, suggests new research.

Scientists say the mixture of three molecules could potentially be given therapeutically to patients to aid in their recovery after serious injury.

After spinal cord injury or stroke, axons originating in the brain’s cortex and along the spinal cord become damaged, disrupting motor skills.

Now, according to findings published in the journal Neuron, a team of scientists at Boston Children’s Hospital in the United States has developed a method to promote axon regrowth after injury.

They administered the therapeutic cocktail of molecules to mice with either a spi- nal cord injury or stroke and observed that the mice were able to recover fine motor skills.

Study senior author Doctor Zhigang He, of Boston Children’s Hospital and Harvard Medical School, said: “In our lab for the first time we have a treatment that allowed the spinal cord injury and the stroke model to regain functional recovery.”

Dr He’s team designed the mixture by building on earlier work with Dr Joshua Sanes group at Harvard in the US, in opticalnerveinjury,whenthey had observed that the combination of insulin-like growth factor 1 (IGF1) and a protein called osteopontin (OPN) promoted nerve regrowth and vision improvement in optically-injured mice.

To investigate whether the combination would influence functional recovery, the team studied a mouse model of spinal cord injury to one side of the body.

Without intervention after injury, the mice were gradually able to recover some major motor function through natural resprouting of their axons.

But, big shortfalls remained in their fine motor skills, making it difficult for them to walk on ladders with irregularly spaced rungs or retrieve food pellets.

In contrast, when the mice were injected with IGF1 and OPN one day after spinal cord injury, their fine motor skills greatly improved.

By week 12, the researchers observed that the mice’s error rates on the irregular ladder dropped to 46 per cent, performing strikingly better than the untreated control group, which still continued to make errors 70 per cent of the time.

Dr He said the improvement was caused by a boost in axon sprouting and regeneration that resulted from the therapeutic mixture.

The team wondered if adding 4- aminopyridine-3-methanol, known to improve axon conduction, into their therapeutic cocktail would further enhance the mice’s functional recovery.

When they gave the cocktail of three molecules, they saw that the mice’s error rates in the irregular ladder task fell to 30 per cent - only 10 per cent higher than the healthy side.

Studying a mouse model of stroke, Dr He’s team made a surprising observation.

He said: “We saw what we expected, axon sprouting in spinal cord.

“But we also found something unexpected, increased axon sprouting in the subcortical area.”

By genetic manipulation Dr He’s team ablated the sprouted axons of the CST and found that the improvement diminished. That means the functional recovery was not particularly dependent on sprouting in subcortical regions but on those in the spinal cord.