Pain, such as the agony of cancer or the anguish of tornnerves, can be a living death.
Contrary to common perception, Stanford Universityanesthesiologist William Brose told BioWorld Today,"pain is not a sensation. If you think of people having fivesenses _ sight, hearing, taste, smell and touch _ pain isnot one of them. Therefore, its sensory component comesunder touch."
Taken together with pain's other two components,personality and experience, he added, "those three makeup the experience of pain."
Brose, who directs the Pain Clinic at Stanford, reportedon Nov. 11, 1995, in Los Angeles, to the 14th annualscientific meeting of the American Pain Society on anexperimental pain-control compound tested on patients athis clinic.
This is a chemically synthesized peptide, SNX-111,discovered and developed by scientists at Neurex Corp.,of Menlo Park, Calif. In six of seven sufferers of terminalcancer pain, or chronic, long-term post-accident nerveinjury, the compound brought dramatic relief, wherehigh-dose morphine therapy had failed.
SNX-111 is a selective calcium-channel-blocking agentthat derives from one of the deadliest toxins known tohumans _ or fish. The cone snail, Conus magus, is amarine gastropod that frequents Australia's Great BarrierReef. Roughly the size and shape of a tapered handgrenade, it kills its piscine prey with a squirt of venompropelled through a barbed dart or harpoon.
That toxin, as Brose told his audience at the oral scientificposter session, "is a combination of over 60 calciumchannel blockers. One member of this extended peptidetoxin family, the N-type blocker acts on the dorsal portionof the human spinal cord, which is associated withmoving the pain sensation up to the brain."
Its synthetic version, SNX-111 is undergoing Phase I/IIclinical trials at six U.S. pain clinics, of which Stanford isthe first to report results.
Like other heavy-duty pain-killers, SNX-111 isadministered intrathecally. That is, a catheter pumps itinto the fluid surrounding the spinal cord. The NationalInstitutes of Health estimates that 1 million cancerpatients per year suffer unbearable pain, and 100,000 ofthem receive some intrathecal (spinal) palliation.
As Brose reported, six of the seven chronic-painsufferers, "all unresponsive to intrathecal opioids, hadpartial or complete pain relief at SNX-111 doses rangingfrom 0.3 to 10 nanograms per kilogram per hour."Adverse effects were minor and reversible.
"All seven," Brose observed, "are thought to havepredominantly neuropathic components to their refractorypain." Neurex estimates that 400,000 patients in the U.S.alone suffer from this kind of pain, of which shingles isan example.
As of 1986, the census reported 79 million people in theU.S. are afflicted with chronic pain, for which the tab indirect and indirect costs approaches $97 billion.
Brose distinguishes neuropathic from nociceptive pain:"which is experienced in response to a noxious stimulant.Neuropathic would be pain described in the absence ofany noxious stimulus." He compares the latter to"abnormal functioning of the nervous system, whichstarts to fire automatically, rather than due to someonesticking a knife in you, or putting a flame to your skin, orof a tumor invading a bone, or pressing on a nerve ororgan."
Three of the five end-stage cancer patients in his clinicalstudy reported "complete relief," the other two, "nearlycomplete" or "partial."
Patients six and seven owed their pain to brachial plexusavulsion injury. That is, Brose explained, "the nerves thatsubserve function to the left arm were traumatically tornaway," in one case by a motorcycle accident, in the other,a skiing mishap. One subject acknowledged "completerelief," the other "no relief."
Brose observed that "these two non-cancer, chronic-painpatients were the more specifically interesting to thegroup of scientists at the meeting. Fully 80 percent of thequestions they asked about the SNX-111 drug and itseffectiveness were directed toward those two patients."
Now that their Phase I/II trial is ended, the seven painsufferers, are being offered an indefinite extension ofSNX-111 therapy, Brose said, "on a compassionate-usebasis, through Neurex."
He added that the company, jointly with Medtronic Inc.,of Minneapolis, Minn., plans to start controlled PhaseII/III trials "of severe cancer pain before the end of thiscalendar year." Medtronic, an investor in Neurex,supplies the intrathecal pumping device that delivers thedrug to the spinal cord. (See BioWorld Today, Aug. 7,1995, p. 1.) The pivotal study will test a similar cross-section of patients at 10 clinical sites, and is expected tolast six months. n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.