|11-28-2001, 08:04 AM||#1|
Join Date: Oct 2001
For Dr. Young re: Pain Research
I've been looking for the right pressure point at the NIH to lobby for pain research into central pain syndrome. In my web wanderings, it looks like the National Institute of Dental and Cranial Research takes the lead on pain research at the NIH. Do you find this to be true?
I came across the info that led me to this conclusion at:
Referenced here is a "newly formed Pain Research Consortium" by branches of the NIH. I had come across this before with a 1997 reference, but no current information.
The end of the exhibit would indicate that the NIH's "strong institutional support" for the NIH Pain Branch may be dead in the water. Any opinions here and ideas how to get it jump started?
The exhibit also references a clinical trial that was to begin using a gene transfer model. Do you have any info on where this is? I've pasted the article below.
Thank you for any info!
PAIN, CNS DISORDERS
TARGET OF NOVEL GENE THERAPY PATHWAY
by Fran Pollner
NIDCR researchers have pioneered a new pathway to ameliorate chronic pain: gene transfer by recombinant adenoviral vector to deliver a b-endorphin gene directly into the meningeal tissues surrounding the spinal cord.
After long trial and error (see "Commentary"), they came up with a magic vector-target combo that induces nonneuronal cells to bathe the cord in analgesic balm.
The minigene is constructed so that the connective tissue cells of the pia mater will secrete b-endorphin into the cord and the
cerebrospinal fluid (CSF). The strategy has relevance for neurodegenerative disorders and spinal cord injuries as well. Part of
the Clinical Center's new bench-to-bedside initiative, the research was done in collaboration with the University of Pennsylvania in Philadelphia.
"We are totally pumped up. This approach is working, at least in the animal model," said Michael Iadarola, explaining his poster
on "Viral Gene Transfer Approaches to Treatment for Chronic Pain" at the NIH Research Festival. Delivery of the b-endorphin gene into the CSF, he said, resulted in the rat's failure to exhibit the typical reaction to pain that would have resulted from an inflamed paw.
The brain or spinal cord tissue is not as hospitable a destination as the CSF space, said Iadarola, chief of the Neuronal Gene
Expression Unit in the NIDCR Pain and Neurosensory Mechanisms Branch. "If you inject a virus into brain tissue, it doesn't percolate well through the limited extracellular space in between neurons-and the axonal tracts form a physical barrier against the virus in three-dimensional space-but injection into the CSF will transduce pia mater cells over a broad area," he said. Both
the poster and a paper to be published in the May 1 issue of Human Gene Therapy were coauthored by Alan Finegold, previously an NIDCR staff fellow and now in the private sector, and UPenn anesthesiologist Andrew Mannes.
It is possible, Iadarola said, that within a year, this "paracrine paradigm" will be tested in humans, in a collaborative NIDCR-NIAMS clinical trial to alleviate pain in terminal cancer patients and, later, in patients with certain inflammatory joint problems-without the side effects associated with opiates.
"Injecting genes into nonneuronal cells to bathe the neurons can work for motor as well as sensory neurons," Iadarola added. "Assuming the disease can be treated with a secreted gene product, like a protein or a growth factor or a neuropeptide, you can go the pial-meningeal route or even into the ependymal cells that line the ventricles or the synovial cells that line the joints. It
is not a direct correction of a genetic defect, but it can provide a paradigm" for Parkinson's, multiple sclerosis, spinal cord injury, and many other central nervous system disorders, he said. It may be especially effective, he added, where large sectors of the brain are involved, with the viral vector reaching into the deep recesses of the sulcal spaces after installation into the
subarachnoid CSF over the cortex.