Important nerve fibers grow again


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After a spinal cord injury, most patients recover only to a limited extent. They remain permanently paralyzed and only a small part of their body functions comes back spontaneously. The reason is that a particular nerve fiber bundle called corticospinal tract hardly regenerates.
This tract begins in the cerebral cortex (cortex) and draws from there into the spinal cord. It consists of axons of more than one million nerve cells and is very important for voluntary control of the muscles of the body, arms and legs.

Boosting effect
The Wings for Life-funded Professor Zhigang He and his working group at Harvard Medical School, now published amazing results. They showed in an experimental animal model, how nerve fibers in this tract successfully grow and sprout again.
The growth factor IGF1 (Insulin like growth factor) influences and promotes the development and growth of nerve cells. After an injury, however, it does not lead to any regeneration of the axons. Only the combination with the protein osteopontin made the cells responsive to IGF and thus led to an outgrowth of the axons of the corticospinal tract.

The right combination
Under the combination treatment of IGF and osteopontin, a certain functional recovery was achieved with a cross-section paralysis. The working group, however, wanted more and administered 4-AP-MeOH (4-amino-pyridine-3 methanol). This active ingredient improves the conductivity of nerves, and is a derivative of 4-AP (4-Aminopyridine), which is used in multiple sclerosis and shows little side effects. In fact, the effect on functional recovery was significantly increased with 4AP-MeOH.

Transverse section of the spinal cord under the microscope:    

Sprouting of axons (red) to the injured side of the spinal cord with IGF
Sprouting of axons (red) to the injured side of the spinal cord with IGF 

Sprouting of axons to the injured side of the spinal cord with OPN
Sprouting of axons to the injured side of the spinal cord with OPN 

Sprouting of axons to the inured side oft he spinal cord with IGF/OPN
Sprouting of axons to the inured side oft he spinal cord with IGF/OPN 

How is it going on?
This result is promising and a first step in clinical application, as the time of treatment - three days after the injury - is clinically realistic and feasible. In a next step, it is important to find a way to administer OPN and IGF1 clinically.

 

Source: “A sensitized IGF1 treatment restores corticospinal axon-dependent functions”. Liu Y, Wang X, Li W, Zhang Q, Li Y, Zhang Z, Chen B, Zhu J, Williams PR, Yu B, Sanes JR, He Z. Neuron, July, 2017.