[TMIC] FW:(RP) From Sally: Article on Central Pain

[Guest guest]

Hi All

I think this article is very interesting and looks like it is promising. One day soon we will be going somewhere for our cure right?? I can keeep on dreaming and someday my wish will come as all of yours. Who ever finds it will or should get the Noble Prize for it!! No one can take our dreams away.

Love ya

Sally

Thought htis might be interest for neuro pain...

February 11, 2002 Talk about it E-mail story Print

Oceans of Hope

The search for potent marine chemicals to treat pain and disease is

steaming ahead. Drugs derived from aquatic creatures are making their way to

the market.

Times Headlines

more >

By LINDA MARSA, Times Staff Writer

Beautiful to look at, but lethal to the touch, predatory cone snails lurk in

the tropical reefs of the South Pacific. They secrete a paralyzing venom

that they inject into their prey. But this poison has also proved to be

something of a medical marvel: a powerful pain-fighting drug for humans.

After more than two decades of trolling the oceans in search of novel

disease fighters, researchers finally are hitting pay dirt. The new pain

treatment, called Prialt, is the first in a wave of marine-based medicines

expected to reach pharmacy shelves during the next few years.

Prialt, which interrupts the transmission of pain impulses in the spinal

cord, is expected to be available within the next year. And more than a

dozen other novel agents, derived from such sea creatures as coral, sponges,

sea squirts and mosses, are under development to treat an array of

illnesses, from asthma to cancer.

Ever since British physician Fleming's accidental discovery in

1928 that ordinary mold destroyed bacteria, a finding that led to the

development of penicillin, scientists have combed swamps, tropical rain

forests and other ecosystems in search of powerful medicinals. More than

half of all prescription drugs, including antibiotics, morphine and the

cancer-fighting drug Taxol, are obtained from naturally occurring products.

But researchers are running out of good leads. Only 1% to 2% of soil

specimens retrieved during medicinal expeditions contain previously unknown

compounds, according to Newman, a chemist with the National Cancer

Institute. In contrast, more than half of extracts culled from sea creatures

are unique, according to Fenical, director of the Center for Marine

Biotechnology and Biomedicine at Scripps Institution of Oceanography in La

Jolla. Not surprisingly, marine drug research, once a scientific backwater,

is now attracting the attention of major drug companies, such as Aventis,

& and Novartis.

" We're trying to find drugs that can do things that nobody could ever find a

drug to do, and some of the test results have been quite remarkable, " said

Fenical. " People realize the ocean is an incredible resource for novel and

biologically active products. "

Though ocean reefs may look like tranquil paradises, beneath the surface

they are sites of intense chemical warfare. Over millions of years, ocean

dwellers have developed a complex repertoire of survival mechanisms, and the

chemicals they secrete to keep predators at bay must be potent enough to

withstand dilution by seawater.

" Organisms that sit on a reef have neither fins, scales, fangs or claws, and

they have to devise ingenious ways of maintaining a toehold on the

reef--otherwise they're dead, " said Newman, who heads the NCI's Natural

Products Branch in Bethesda, Md. Algae and sea grass, for example, secrete

noxious-tasting chemicals to discourage fish from nibbling on them.

But how can compounds that work for sea creatures also help humans? The

answer lies in the fact that we share about 5,000 genes with marine

organisms, which possess primitive versions of human systems. " It doesn't

matter whether you're a microbe or a man, " said Newman. " The genes fulfill

almost the same function. "

Scientists are hopeful that these marine drugs may prove more effective than

some current therapies. Scientists say Prialt (whose generic name is

ziconotide), for instance, the pain remedy derived from cone snails, will

revolutionize treatment of severe, chronic pain because the targeted therapy

doesn't have the unpleasant side effects of morphine or other opiates--it's

not habit-forming and it doesn't envelop users in a narcotic fog.

" It's quite exciting because this treats pain conditions that haven't

responded to conventional therapy, " said Dr. S. Leong, an assistant

professor at the Stanford University School of Medicine, who tested Prialt

on 108 people with cancer and AIDS. " All these patients had exhausted

everything that was available, and even the worst patients with intractable

pain got some relief. "

Researchers knew the snail's venom affected the central nervous system. But

they discovered it was a potent painkiller quite by accident. A laboratory

analysis of the toxin indicated that one component blocked calcium channels,

the chemical pathways that help cells communicate with one another.

Prialt blocks nerve impulses in a key region of the spinal cord, where pain

fibers from the body connect with the nerve cells that send pain signals to

the brain, said Baldomero M. Olivera, a biology professor at the University

of Utah in Salt Lake City, who first isolated the snail venom in 1980.

This is why Prialt, which is 50 times more potent than morphine, is so

exquisitely precise and doesn't cause the adverse effects of opiates: It

stops pain messages from getting through while allowing the rest of the

nervous system to function normally.

Another component of the cone snail toxin, which prevents nerve damage, is

in the early stages of tests on people suffering from severe epilepsy.

The U.S. Food and Drug Administration has granted preliminary approval to

Elan Pharmaceuticals, the Ireland-based maker of Prialt. If it gains final

FDA clearance, as expected, it could be available within the year. It is

expected that Prialt's use initially will be limited to patients with

intractable pain, from cancer, AIDS or severe back problems, because the

drug must be administered by catheter directly into the spinal fluid.

In the future, however, this therapy may have broader applications. " This

promises to be the first of a whole new class of pain drugs, " said

Stanford's Leong. " We may be able to use it to treat people resistant to

other types of drugs. "

Another promising marine drug is derived from a moss-like creature found in

the waters off the West Coast. The drug, bryostatin, is a cancer-fighting

compound that is in the second phase of testing on humans. (Normally, drugs

go through three phases of clinical trials before companies apply for FDA

marketing approval).

Bryostatin is produced by tiny bacteria that live inside Bugula neritina, a

sea organism that often clings to the hulls of boats like barnacles.

Bryostatin seems to work by throwing a monkey wrench into the DNA of cancer

cells, halting the unchecked cell growth of cancer. By itself, bryostatin

isn't very effective. But it seems to enhance the activity of such

chemotherapies as Taxol and cisplatin.

At Memorial Sloan-Kettering Cancer Center in New York, for example,

bryostatin is being tested in combination with Taxol on patients suffering

from cancer of the esophagus, which is difficult to treat. Preliminary data

indicates that in 60% of patients, tumors shrink by at least half versus a

response rate of 17% from Taxol alone.

Dr. K. Schwartz, an oncologist at Memorial Sloan-Kettering who is

conducting these trials, believes that the substances are a big step forward

but said researchers must overcome the treatment's side effects--severe

muscle aches, which afflict some patients. " If we could find a way to

[minimize the muscle aches] and maintain that response rate, we're going to

have a home run, " he said.

Bryostatin and Taxol may be used in tandem to treat cancers that respond to

Taxol, such as breast, ovarian and lung cancer. Despite these dramatic

benefits, scientists still haven't devised a method of making enough

bryostatin for commercial use. Fourteen tons of Bugula neritina harvested

from waters off the coast of California yielded a paltry 18 grams of

bryostatin.

" All of the drug trials that are going on are using material from that one

batch of bryostatin, which gives you an idea of how potent it is, " said

Margo G. Haygood, an associate professor at Scripps. " But continuing to

collect enough of the animals out there to produce this for people to use

would be environmentally destructive. "

The alternative is to find a way to produce bryostatin in the laboratory.

Haygood's research team is attempting to identify the gene responsible for

triggering production of bryostatin. Once they do that--and they're

tantalizingly close--they'll smuggle the genetic material inside bacteria,

which replicate exponentially. These colonies of genetically altered

bacteria are transformed into mini-bryostatin factories because each

bacterium is then programmed to secrete the substance. Still, said Haygood,

" it's a big challenge to crack this problem. "

Sea squirts, which live in clusters in the temperate waters off the

Caribbean and Mediterranean seas, contain another potent anti-tumor agent,

ecteinascidin. Scientists have chemically synthesized the active ingredient

in the sea squirts to formulate a drug, ET-743, which has been used in small

studies of patients with advanced breast, colon, ovarian and lung cancer.

Researchers also are testing it on patients with advanced sarcomas,

malignant tumors that grow in muscles, fatty tissue and bones. In early

testing, tumor progression was slowed or halted in nearly half of the

patients, and more than half survived more than a year, a much better result

than with chemotherapy. " These patients are very hard to treat because their

disease is so advanced, " said Dr. D. Demetri, an oncologist at the

Dana-Farber Cancer Institute and Harvard Medical School in Boston . " Yet

some of them had their tumors totally melt away; sometimes miracles happen

for reasons none of us can explain. "

Though this therapy is not yet on the market, it's already dramatically

affecting people's lives. For Fran Skutta, ET-743 was a lifesaver. The

51-year-old Greenville, S.C., woman was first diagnosed with lipo sarcoma in

December 1992. Doctors removed a 10-pound tumor from her abdomen that had

wrapped itself around one kidney. In 1999, the cancer returned with a

vengeance, and this time surgeons were forced to cut out almost a third of

her colon. By 2000, the tumor was so immense that it was inoperable.

Skutta's doctors told her she probably had fewer than five years to live. In

desperation, Skutta enrolled in the clinical trial at Dana-Farber Cancer

Institute in January 2001. Now, 13 months after she began treatment with the

experimental drug, her tumor has shrunk by more than 70%. " This drug has

given me my life back, " said Skutta, who flies to Boston for treatment every

four weeks.

Not quite as far along in development is a group of anti-inflammatory

compounds that seem to be as effective as steroids but thus far appear not

to have the same adverse effects, such as organ damage, loss of bone density

and stunting of growth in children. Typically, when a pathogen enters the

body, white blood cells, the foot soldiers of the immune system, are

dispatched to the infected area to destroy intruders. But the accumulation

of these cells, which surround the invader to prevent it from spreading,

causes the swelling and redness we associate with infection.

These novel agents, called LSAIDs (leukocyte-suppressing anti-inflammatory

drugs), damp-en this immune response " by inhibiting the migration of white

blood cells to the site of inflammation, " says Bacha, a vice

president of Inflazyme Pharmaceuticals, a Vancouver, B.C., biotechnology

firm. One of them, IPL576092, a chemically synthesized version of a compound

found in sea sponges that inhabit waters near Papua, New Guinea, is being

tested on asthma patients to relieve chronic lung inflammation and airway

constriction. Preliminary research suggests the oral drug works as well as

inhaled steroids, the current standard treatment.Similar agents derived from

these sponges are also being tested to stop the nerve damage that typifies

multiple sclerosis and the painful joint swelling of rheumatoid arthritis.

Eventually, these drugs may be used to control other inflammatory diseases

of the skin, bowel and lungs.

Another promising source of anti-inflammatory drugs are pseudopterosins,

chemicals made by plants that live on soft coral found in the Caribbean Sea

near the Bahamas. Pseudopterosin extracts have been used for nearly a decade

by cosmetic companies, such as Estée Lauder, as an additive to prevent

irritation caused by exposure to the sun or the chemicals in the cosmetics.

But the major roadblock standing in the way of its development as a drug for

treating severe burns and allergies, or to accelerate wound healing, is that

scientists still don't have the tools to make enough pharmaceutical-grade

pseudopterosin to test it on humans. " Supply is always a problem with marine

products because you're invading delicate ecosystems to collect organisms

for commercial purposes, " said s, a professor of pharmacology at

UC Santa Barbara. " But we're getting close to isolating the DNA that

produces the chemical. "

Despite these strides, marine drug development is still in its infancy, and

the oceans may soon yield more powerful medications. " It's taken roughly 30

years to get where we are, " said the NCI's Newman. " But given that

fact that the ocean is home to more than two-thirds of the world's species,

this is only the beginning. "