Contact:          Tania Banak, University Relations Specialist
608/263-6716, banakt@svm.vetmed.wisc.edu
Date issued:    March 6, 2008

MADISON – Victims of spinal cord injury who’ve been forced to rely on mechanical assistance to breathe may “breathe easier,” so to speak, if progress continues on development of drugs that encourage their body to compensate and minimize the extent of paralysis. 

For years, Dr. Gordon Mitchell, a professor of comparative biosciences at the University of Wisconsin-Madison School of Veterinary Medicine, has studied respiratory plasticity, or the body’s ability to adapt breathing so that it remains adequate despite challenges throughout life.  Now, his laboratory’s latest development holds promise for individuals whose breathing control is impaired.

Over years of study, Dr. Mitchell’s laboratory group has identified key proteins that cause respiratory plasticity when, for example, the body experiences repeated bouts of low oxygen. 

“My hope is to harness this inherent ability to benefit patients with breathing control disorders, such as sleep apnea, or respiratory impairment caused by spinal injury or neurodegenerative diseases,” Dr. Mitchell says.

Recently, along with Dr. Frank Golder (now at the University of Pennsylvania), Dr. Mitchell has made progress in that direction.  By using a drug that activates the right kind of protein receptors in the spinal cord, the researchers were able to mimic and even enhance the body’s natural ability to use respiratory plasticity.  When these same drugs were given to rats with inadequate breathing due to spinal injuries in their neck, breathing deficits were reversed and breathing returned to normal.  Their work was published in the February 27, 2008 issue of the Journal of Neuroscience.

“Although the response may be modest, even small increments in respiratory function can significantly enhance quality of life in ventilator-dependent patients,” Dr. Mitchell said.  “That’s particularly true if the gain in breathing function allows even partial independence from the ventilator.”

The drug acts by stimulating important proteins that trigger adaptive nerve responses, or plasticity.  The drug is a smaller molecule (known as an adenosine 2A receptor agonist) that can be delivered by intravenous injections since it readily crosses from the blood into the spinal cord. 

Prior to this development, drugs that have stimulated the desired response have been difficult to deliver to the spinal cord, or have not worked effectively over the long-term.  This new method of respiratory stimulation holds promise for maintaining breathing function over longer periods.

“If we could enhance respiratory function in patients paralyzed from a spinal cord injury at the neck, it would greatly improve their quality of life and their survival rate, and that is an important goal,” Dr. Mitchell says.