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Cancer Drug for SC?

Reprinted from PN January 2012

Taxol is a drug used to treat a variety of cancers. It could be considered for treating spinal-cord injury.

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Originally isolated from the bark of the Pacific Yew tree, Taxol is a drug used to treat a variety of cancers, including lung and breast. Intriguing animal research shows it may also be good for spinal-cord injury (SCI). Because of its extensive use as a cancer treatment, much is already known about Taxol’s interactions with the human body. In theory, such understandings should accelerate its consideration as an SCI treatment.

Microtubules

Through stabilizing key structural components within the cell called microtubules, Taxol interferes with the division of cancer cells and, hence, slows tumor growth. Microtubules are, so to speak, the protein “girders” that help create cell infrastructure and, depending upon how these girders are assembled, cell destiny. Basically, Taxol stabilizes this infrastructure by strengthening connections between girders with additional molecular-bond rivets. In the case of cancer, these rivets prevent the cells from assuming the more malleable structure required for cell division and, in turn, tumor growth. With SCI, Taxol stabilizes microtubule structure after injury in a way that increases the regenerative potential of damaged neuronal axons.

Growth Cones vs. Retraction Bulbs

Considerable animal research evaluating Taxol’s regenerative influence on neurons has been carried out at various institutions in Germany and the U.S. Much of this research has focused on a damaged neuron’s propensity to develop a growth cone or retraction bulb after injury. Generally, regenerating neurons, especially those in the regeneratively inclined peripheral nervous system (i.e., outside the brain and spinal cord), have a growth cone at their axonal tips. This cone contains an abundance of the physiological machinery and substrates necessary for axonal elongation. In contrast, damaged central-nervous-system neurons usually form nonregenerating swellings called retraction bulbs at the tip of their axonal stumps—essentially the non-growing equivalent of growth cones.

A key difference between growth cones and retraction bulbs involves the degree of microtubule assembly. When assembled in parallel bundles, microtubules are the backbone of axonal shafts with growth cones. They lay the tracks for bringing in needed molecules, cellular structures, and energy supplies to the rapidly advancing growth cone; and by so doing,
help push the axon forward. In contrast, retraction-bulb microtubules are disorganized; rather than a backbone, it’s more like a “collection of unconnected vertebra” that can’t support elongation.

If microtubule structure is experimentally destabilized in a growth cone, it becomes more like a refraction bulb, and, as a consequence, axonal growth stops. On the other hand, Taxol-induced microtubule stabilization reduces retraction-bulb formation after CNS injury. After Taxol treatment, the axonal endings now resemble growth cones and are better able to push through the inhibitory, environmental gauntlet characteristic of the injury-site scar.

Scar Reduction

An article published in Science Magazine (Hellal, F. et al., 2011) summarized evidence that Taxol also reduces injury-site scarring after SCI. Specifically,  investigators showed that Taxol reduces the amount of regeneration-inhibiting substances that accumulate at the injury-site scar. As a result, the inhibitory gauntlet the axon must pass through to reach its target has been weakened. Specifically, the number of axons making it through increased fivefold after Taxol treatment, and, as a result, treated animals with SCI regained 3.4 times more ambulatory ability than controls.

Contact: laurancejohnston@msn.com.

 

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Cancer Drug for SC?

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