|10-09-2001, 11:30 AM||#1|
Join Date: Sep 2001
Location: St. Louis, MO
Axonal transport of pain drugs
I just got this from a list I belong to for central pain patients. This sounds like something with real potential.
Tuesday, October 09, 2001
New discovery may revolutionize treatment for pain related to surgery,
illness and injury
University of California - Los Angeles
For those suffering from pain, scientists from UCLA and the University of
Cambridge, United Kingdom, report a revolutionary advance in pain medicine
that promises to deliver painkillers directly to the affected area of the
body, in smaller doses and with fewer side effects.
The researchers report the first clinically suitable method using nerves as
a means of safely delivering high doses of painkillers to achieve a
therapeutic effect. They announced their research findings at the Society
for Neuroscience conference on Nov. 8 in New Orleans, La.
UCLA neurosurgeon Aaron Filler and his colleagues used a method called
"axonal transport" to deliver a pain drug to the spinal ganglia and spinal
using nerves as a conduit, in an animal model.
Axonal transport works like a "conveyor-belt" process, delivering
medication to remote sensory endings in the tissues of the body. In axonal
transport, the cell moves molecules from one end of the cell to the other,
supporting their ability to communicate with other neurons. A single neuron
be more than two feet long.
Although axonal transport has played a role in thousands of research studies
the past, this is the first-ever report of a positive clinical effect with a
potential human medication. The new technology uses a novel molecular
structure to achieve clinically effective dosing in targeted groups of
nerves, Filler said.
This work marks an important advance, because drug treatment of
nervous-system disorders is often hindered and sometimes precluded when the
precise site of the injury or disease cannot be reached with adequate levels
pain medicine without causing unwanted side effects. Delivery of painkillers
directly to selected target sites can avoid undesired toxicity, as well as
inappropriate side effects in non-target neural tissue.
Filler says that with this new method of delivering pain medication, one
administered during surgery could alleviate the pain sensations a patient
normally feel for several days. The painkillers will go only to the nerves
involved in the surgery, eliminating the negative side effects patients
experience from the current method of pain treatment such as nausea,
drowsiness and impaired breathing.
The researchers found that appropriately formulated substances, including
are taken up by axon nerve endings and transported to the core tissues of
nervous system. Since nerves are territorial and map out particular segments
the body, this allows the selective delivery of drugs to relevant parts of
nervous system involved in pain sensation and other disease processes.
The researchers created a complex made up of an axonal transport facilitator
(ATF) attached to a linker molecule bearing up to a hundred reversibly
drug molecules. This complex was configured to deliver the drug gabapentin
rat model of neuropathic pain to selected dorsal-root ganglia by axonal
transport after injection into tissue supplied by the target nerves.
"This very complex design achieves something that, previously, was not
possible," Filler said. "The way it works makes this the first truly
21st-century medication. These results are expected to lead to dozens of new
medications that will solve difficult drug delivery problems in the
treatment of conditions as varied as stroke, Alzheimer's disease, shingles
"A single injection of the ATF drug complex caused a 50 percent reduction in
hypersensitivity to pain that lasted up to four days," says Filler. "To
achieve a similar effect by the current drugs would require more than 300
times the amount of painkiller given in multiple doses."
The current method of pain treatment involves delivering painkillers into
the blood stream. The pain medication then travels throughout a patient's
system, affecting all areas of the body, unlike this new, targeted approach.
Clinical trials using axonal transport to treat neuropathic pain will begin
in early 2002.
In addition to Filler, Dr. Andrew Lever, Dr. Raj Munglani and Dr. Garth
Whiteside of the University of Cambridge; and Dr. Mark Bacon, Dr. Jonathan
Clark and Dr. Peter Laing of SynGenix Ltd. all collaborated on this
The research was funded by SynGenix Ltd., the UK Department of Trade &
Industry, and the Neuroscience Research Foundation of Atkinson Morley's
Filler is a co-founder, consultant and significant shareholder of the
pharmaceutical firm SynGenix Ltd. of Cambridge, United Kingdom, which in
part funded this research, and holds the rights to the axonal transport