Role of ATP in Spinal Cord Injuries Revealed

A few weeks ago, Physicians Committee for Responsible Medicine called for an end to classes in spinal cord injuries that included specific techniques for creating animal models for such injuries. A recent discovery by a team at the University of Rochester Medical Center, however, underscores the important role that animal research plays in understanding complex changes in biological systems.

The short version is that researchers found that ATP — an energy source cells need to stay alive — plays an important role in causing damage to otherwise healthy cells after trauma in the spinal cord. After a spinal cord injury, ATP levels increase up to 100 times normal levels. Undamaged neurons essentially become over-stimulated and they die from metabolic stress.

According to a University of Rochester Medical Center press release,

The finding that ATP is a culprit in causing the devastating damage of spinal cord injury is unexpected. Doctors have known that initial trauma to the spinal cord is exacerbated by a cascade of molecular events over the first few hours that permanently worsen the paralysis for patients. But the finding that high levels of ATP kill healthy cells in nearby regions of the spinal cord that were otherwise uninjured is surprising and marks one of the first times that high levels of ATP have been identified as a cause of injury in the body.

Using an animal model of the disease opposed by PCRM — in this case in rats — the researchers created a compound that blocked the effect of ATP on neurons in the animals’ spinal cords after injury. The result? After six weeks the rats’ spinal cords had recovered most of their function and they were able to walk, run and climb as well as a healthy control group of rats.

Source:

Scientists finger surprise culprit in spinal cord injury. Press Release, University of Rochester Medical Center, July 28, 2004.

Animal Research Points to Possible Treatment for Severe Chronic Pain

Research published recently in the Journal of Clinical Investigation suggests that severe chronic pain might be treated by selectively deleting specific nerve cells that convey the pain through the nervous system.

A research team led by the National Institutes of Health in April reported that a series of experiments in rats demonstrated that a drug called resiniferatoxin could be injected in the ganglia of rats and selectively kill some cells while allowing the rats to maintain normal motor and sensory function. The researchers then followed up by using the technique to treat dogs suffering from chronic pain.

The researchers used eight dogs who had been brought to veterinary hospitals with severe pain from arthritis and cancer. The dogs were injected with resiniferatoxin to kill the neurons responsible for the sensation of chronic pain felt by the dogs. According to a press release from NIH on the study,

So effective was the treatment in eight dogs severely affected by osteroarthritis, cancer-related pain, or both, all eventually became more active and later walked with slight or no limps. Just as importantly, none showed any adverse side effects from their treatments, their temperaments were improved, and their need for other pain-controlling medications was eliminated or greatly reduced.

In addition, the pain relief the dogs experienced did not diminish as their disease progressed. Dr. Michael Iadarola said in a prepared statement,

We were very encouraged to see a long-term therapeutic benefit that did not diminish with the progression of the disease. When a cancer progresses, you often have to increase the dose of conventional pain medications, such as opiate analgesics, which can produce alterations of consciousness, activity level, and other severe side effects that can impair overall quality of life.

Source:

Animal studies show promise treating severe chronic pain. Press Release, National Institute of Dental and Craniofacial Research, May 3, 2004.

Researchers Clone Rat

In September researchers from China and France announced they had managed to clone rats, adding it to the growing list of animal species that have been successfully cloned.

Figuring out how to clone the rat took considerably longer than the mouse (which was cloned in 1998) due in part to the speed with which rat embryos develop — the eggs would start to develop before researchers could swap genetic material to produce the clone.

French researchers solved that problem by using an inhibitor to delay the development of the fertilized rat egg long enough to insert the clone DNA material.

Rats are used in a number of animal models where they are closer analogues to human physiology than mice (such as diabetes for one), and the ability to clone rats and make gene knockout rats will greatly aid research into a variety of human ailments.

Sources:

Rat Clone Is New Big Cheese of the Lab. Los Angeles Times, September 26, 2003.

Rat is latest clone. The BBC, September 25, 2003.

Embryonic Stem Cells Cure Parkinson's-Like Disease in Mice

In September, U.S. researchers reported in Nature Biotechnology that they had used stem cells to cure mice who were bred to suffer from a Parkinson’s-like condition.

Researchers at the Stem Cell and Tumor Biology Laboratory took cells from the tails of the mice and used that to clone embryos. Stem cells from the embryos were then taken and altered to grow into a type of brain cell that the mice were missing. That tissue was then implanted into the brains of the mice.

The researchers reported that the Parkinson’s-like conditions in the mice disappeared after the tissue implant.

Dr. Lorzen Studer, lead research on the study, told the BBC that this research provided a proof of concept that embryonic stem cells could be used in this way, but that there are still many hurdles to overcome before this could be tested on human beings (not the least of which, in this case, would be the creation and use of embryonic stem cells which is still the subject of much ethical hand wringing).

Studer added that,

We don’t know if we would be able to do the same thing in humans — there is some research, which is controversial — that suggests that it might actually be impossible.

A similar study in 2002 also produced positive results when stem cells from mouse embryos were altered to produce brain tissue and then implanted into rats. That study, conducted at the University of Minnesota, showed that the transplanted stem cells grew into neurons in the brains of the rat and improved — though didn’t completely erase — the Parkinson’s-like symptoms suffered by the rats.

Source:

Mouse cloned to cure Parkinson’s. The BBC, September 21, 2003.

Embryonic Mouse Stem Cells Reduce Symptoms in Model for Parkinson’s Disease. National Institute of Neurological Disorders and Stroke, June 25, 2003.

Man Acquitted of Aiding Rats

A man charged with attempting to thwart rat eradication efforts on an island off the coast of California was acquitted in July of the charge against him.

Bob Puddicombe, 52, stood accused of scattering an antidote to rat poison on Anacapa Island. National Park Service officials spread rat poison on the island in an effort to eradicate black rats. The rats are a nonnative species to the island and were threatening native species.

U.S. Magistrate Willard McEwen Jr. acquitted Puddicombe, finding that federal prosecutors had not provided sufficient evidence to convict Puddicombe.

The Associated Press quoted Puddicombe as saying, “I only wish the animals on Anacapa could have gotten the same fair trial I did.”

Source:

Calif. magistrate clears rat supporter. Associated Press, July 11, 2003.

Ohio State University Set to Expand Animal Research Facilities

Ohio State University, which came under fire recently over HIV research involving felines, recently announced that it plans a major expansion of its animal testing facilities.

The Columbus Dispatch reported that OSU will undertake a $30 million expansion of its animal testing facilities at Weiseman Hall that will add 35,000 square feet of lab space. The money will be raised through a combination of money from the Ohio legislature and bonds issued by OSU.

OSU’s William Yonushonis told the Dispatch,

It will be a rodent facility, primarily for mice. We’re looking at housing up to 35,000 cages. You can put up to five mice a cage.

This would add to the approximately 75,000 animals that the Dispatch reports are already used annually for research at OSU. Ninety-two percent of such animals are mice and rats.

Ohio-based animal rights group Protect Our Earth’s Treasures criticized the expansion. POET director Rob Russell told the Columbus Dispatch,

There’s a whole bunch of projects that we feel could be stopped today, and we feel it wouldn’t have any negative impact on humans.

OSU is also planning to build a new biosafety level 3 laboratory to study infectious diseases which will house laboratory animals.

Source:

New labs for mice planned at OSU. Alice Thomas, The Columbus Dispatch, July 5, 2003.

Background On Proposed BSL3 Laboratory Planned for Ohio State University’s West Campus. Press Release, Ohio State University, July 26, 2003.