By Sam Maddox
The anti-cancer drug taxol appears to block inhibitory substances and reduce scarring after spinal cord injury. The drug, derived from the bark of the Pacific yew tree, is commonly used to treat several types of cancer, including breast, ovarian and lung, as well as Kaposi's sarcoma in people with acquired immunodeficiency syndrome (AIDS).
It works by as a mitotic inhibitor, thereby preventing cancer cells from dividing. In spinal cord injury experiments with acutely injured animals, taxol is used in a lower dose that does not block cell division; it appears to reduce the effect in inhibitory substances in the area of injury. How so? In cancer the drug ties up microtubules, the “bones” of the cytoskeleton or cell structure. In the spinal cord, taxol is believed to stabilize these microtubules and therefore maintain the architecture of nerve cells. It also appears to kick-start axon growth.
It is well known that axons can’t regenerate in the lesion area of the spinal cord due to a host of inhibitory factors and glial scarring. There have been many studies showing robust regeneration if the lesion area is modified. Currently in clinical trial is a molecule that targets the inhibitor NOGO and blocks it out of the way so axons can pass by. Other possible treatments to reduce inhibition include the enzyme chondroitinase ABC, which targets scarring. Strategies also include reducing immune response.
The taxol work came from an international team, including scientists at the Miami Project and Kennedy Kreiger Institute. PI (principal investigator) was Frank Bradke of the Max Planck Institute of Neurobiology in Germany.
Verbatim from the published abstract:
Moderate microtubule stabilization decreased scar formation after spinal cord injury in rodents via various cellular mechanisms, including dampening of transforming growth factor–β signaling. It prevented accumulation of chondroitin sulfate proteoglycans and rendered the lesion site permissive for axon regeneration of growth competent sensory neurons. Microtubule stabilization also promoted growth of central nervous system axons of the Raphe-spinal tract and led to functional improvement. Thus, microtubule stabilization reduces fibrotic scarring and enhances the capacity of axons to grow.
Here’s what Bradke told the press about inhibitory factors, taxol and SCI: “Inhibitors act like stop signs for these axons.” He said the idea is to either take away some of the stop signs, or get the nerve cells to act like a “mad driver” and ignore them.
“The good thing about taxol is that it actually does both things at once,” Bradke said. “On the one hand, it basically gets these neurons to start to grow, like a crazy driver, and at the same time, it also reduces these stop signs, it reduces the scarring process. With taxol, he said, “You basically manipulate the two major impediments to axon regeneration.”
In rats, taxol decreased the amount of scarring in axons, and stimulated their growth more than placebo. It also improved function; injured rats treated with taxol frequently made fewer missteps on a specific walking task, Bradke said. This work is still early and has not been tested in people, but Bradke pointed out that taxol is already approved for human use, which could speed the process of clinical trials along. “We are still in the state of basic research and a variety of obstacles remain - and eventually, pre-clinical trials will need to be done,” said Bradke. “However, I believe that we are on a very promising path.”
The Bradke paper, Microtubule Stabilization Reduces Scarring and Causes Axon Regeneration after Spinal Cord Injury, was published January 27 in Science Express, the advance online publication of the journal Science.
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