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Scientist known for groundbreaking advance in spinal cord repair

champions new global effort to repair trigeminal nerve







Beyond the retirement pleasures of longer hours on the golf course and with grandchildren,
Neuroscientist Douglas K. Anderson, Ph.D., wants to score a hole-in-one in the search for a cure for trigeminal neuralgia. It's a cause he adopted after meeting people with crippling, unrelenting facial pain.

"We have this large cadre of men, women and children-some as young as two-who need nerve repair because medical science has no way to permanently stop their pain," said Anderson, scientific advisor to The Facial Pain Research Foundation. He refers to the trigeminal (three-part) nerve that energizes facial functions and is prone to injury or deterioration that prompts agonizing pain.

"Trigeminal neuralgia and similar nerve-related facial pain syndromes are orphan diseases, but they are hugely important in terms of pain that destroys people's lives," he said.

He said serendipity brought him into contact with TN patients and the health-care professionals who care for them, and one thing led to another-compassion for people in terrible pain, an unquenchable interest in solving medical mysteries and enthusiasm for joining esteemed colleagues in a new scientific venture.  His interest was kindled in the fall of 2004 when UF Neurosurgeon Al Rhoton invited him to the national conference of the
Trigeminal Neuralgia Association (TNA) meeting in Orlando. While talking to patients and researchers, including a scientist from the National Institutes of Health, he discovered TN is a silent epidemic that suffers from the lack of public awareness and research funding.

"I realized if we want to succeed in finding a cure, we must build our own program supported by private gifts," Anderson said. "We need to become our own
funding agency and set the directions for research aimed at this single goal."  

He returned to his office at UF's College of Medicine where he chaired the Department of Neuroscience, and wrote the business plan for a facial pain research program at UF. In 2009, Lucia Notterpek, Ph.D., who succeeded Anderson as chair of the neuroscience department, initiated the study, which is now part of The Facial Pain Research Foundation's international scientific consortium. Nationally known pain expert Allan Basbaum, Ph.D., at the
University of California San Francisco also has been added to the consortium, which is due for rapid expansion as other world-class scientists are enlisted.

"The fundamental problem we confront in research is why the trigeminal nerve goes bonkers, why excellent corrective surgery ends the pain for some patients, but not for others, why the best available pain-relieving medications help some and not others, and why many patients gain no lasting benefit from any conventional or alternative therapy," he said.  

Anderson said he is optimistic that a breakthrough in the treatment of trigeminal neuralgia, the most extreme facial pain disorder, will reveal therapeutic approaches worth evaluating in the treatment of other nerve diseases, which might include
multiple sclerosis. Both trigeminal neuralgia and multiple sclerosis involve loss of myelin coating around the nerves. 

He added that the trigeminal nerve is relatively easy to access, compared to nerves deep in the spinal cord, and therefore is a good model for myelin research. The nerve can be accessed in laboratory animals for testing ways to restore myelin and repair the nerve.      

In a career that spanned almost 35 years, Anderson achieved a breakthrough in spinal cord repair research by directing finely focused laboratory studies toward clinical application. Through meticulous basic studies of spinal cord physiology in rats and in a small number of cats, he and a team of colleagues gathered data that paved the way for the historic nerve tissue transplants in 1997. The injections of embryonic tissue were limited to patients who had suffered
spinal cord injury and also developed cyst-like wounds (syringomyelia), which cause severe pain and progressive loss of sensation and movement. 

Through this clinical pilot study, a surgeon at UF's
Shands Hospital performed nine surgeries on eight patients. A report in the September 2001 issue of the Journal of Neurotrauma concluded that the Florida team demonstrated the feasibility and safety of nerve tissue transplantation in people with spinal cord injuries. With the use of magnetic resonance imaging (MRI scans) the researchers found that the fluid-filled cavities were filled, becoming a solid mass of tissue-a significant outcome even though the scans were difficult to interpret to distinguish between the patient's tissue and the transplanted tissue. 

The team also found that the nerve tissue transplants halted expansion of the wounds and prevented further loss of function. In follow-up studies continued almost three years after the tissue transplants, the researchers documented changes in the pain sensations reported by the patients. 

"Some of the transplant recipients indicated changes in the character of their pain to the point it was no longer intolerable," Anderson said. "One patient said the pain regressed from 'intolerable to feeling like cold cement.'"            

The pilot study broke new ground by answering important questions regarding nerve tissue transplantation in human patients, and by providing a template for further efforts to restore function after spinal cord injury.

Anderson said one clinical study currently underway in San Francisco involves cellular transplantation within two weeks after spinal cord injury. Quicker treatment is expected to increase chances for restoring the function of damaged nerve fibers. 

"I have come to the conclusion that injecting
stem cells and expecting them to rewire the injured spinal cord and improve function may be as challenging as going to Jupiter," he said. "But now there are strong scientific indications that restoring activity in only ten percent of appropriate nerve tracts in the spinal cord would improve the neurological outcome. If we could put in a stem or progenitor-type cell that would restore the myelin coating around the demyelinated and non-working nerve fibers, it could improve functional activity in patients with chronic spinal cord injury."

"The same approaches being investigated for spinal cord injury can be applied in efforts to restore the
myelin sheath that insulates the trigeminal nerve," Anderson said. "One strategy would be to inject stem cells, or remyelinated (recoated) cells to repair the gaps where myelin has been chipped away, and to reduce pain resulting from nerve damage."

Anderson emphasizes the importance of Notterpek's study, which involves both the development of an animal model of trigeminal neuralgia and an effort to figure out whether genetic differences may explain why myelin damage causes excruciating facial pain in some patients, but not in others with the same type of damage.  

To define the possible role of genes in trigeminal nerve damage, Anderson suggests studies are needed to analyze the genetic makeup of patients with trigeminal neuralgia, and people without the disorder.

For now, Anderson is aiding establishment of The Facial Pain Research Foundation by sharing his wealth of experience in
central nervous system research and by helping to recruit eminent scientists to the consortium.  

Prior to his retirement in 2006, Anderson served a year as interim executive director of UF's McKnight Brain Institute, chaired the Department of Neuroscience for 10 years and for one year served as Deputy Director of the Department of Veterans Affairs Medical Research
Service in Washington D.C.  For many years, he occupied an endowed faculty position as the C.M. and K.E. Overstreet Eminent Scholar, funded by the Overstreet family in Florida. He is a former president and founder of both the National Neurotrauma Society and the International Neurotrauma Society. He earned his Ph.D. in physiology at Michigan State University and completed post-doctoral training in physiology as a National Research Council Research Associate.



 
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