Drug Companies and Neuropathy

Beginning a week of posts related to the drug companies, this article from United Press International(see link below) predicts huge profits for the drug company that produces effective drugs to combat neuropathy...the problem is; this article is from September, 2005!!
If you read their list of drugs used at that time, you'll see no difference to those used today...six years later! It wouldn't be so bad if the drugs worked for more than a small percentage of patients but...six years...and nothing new? Actually, the article was written six years ago but the problem is a lot older. In times of world wide austerity, we're going to need to make our voice heard...the competition for research grants and extra cash is murderous!

Neuropathic pain a lucrative drug target
By ASTARA MARCH

WASHINGTON, Sept. 19 (UPI) -- The company that can develop an effective, easy-to-use drug specifically for neuropathic pain should enjoy outstanding revenues, industry analysts predict.

Datamonitor PLC, a business information company in London, reported this outlook in a statement released last week. The company looked at seven major markets -- including the United Kingdom, the United States, Japan, France, Germany, Italy and Spain -- and found that among $2.5 billion in sales for pain drugs, not one compound has been developed specifically for neuropathic pain use.

Unlike nociceptive pain, which is a message from an injured area of the body to the brain that subsides when the injury heals, neuropathic pain seems to be generated by the nerves themselves. There usually is no active injury present when the pain is experienced, and it often grows worse over time.

Remedies for nociceptive pain, such as NSAIDs and opioids, do not work for neuropathic pain, which is only marginally affected by opioids and responds best to anti-convulsants and tricyclic anti-depressants that block the brain's neurotransmitters.

The classic example of neuropathic pain is phantom-limb syndrome after amputation. Although a part of the body has been removed, the patient often experiences what feels like stabs of pain throughout the missing extremity (neuropathic pain is often described as stabbing, searing or burning).

Diabetes, AIDS, multiple sclerosis, fibromyalgia, chronic-fatigue syndrome, reflex sympathetic dystrophy, Lyme disease and shingles (caused by a virus similar to chickenpox) also produce neuropathic pain, and people with these problems will form a large part of the projected neuropathic pain drug market.

As of June 2005 only five drugs had been approved by the Food and Drug Administration to treat neuropathic pain:

gabapentin, marketed by Pfizer as Neurontin, the gold-standard drug used in over 50 percent of cases and originally developed to treat depression;

lidocaine, marketed by Endo Pharmaceuticals as Lidoderm, a local anesthetic;

carbamazepine, originally marketed by Novartis as Tegretol, an anti-convulsant;

duloxetine, an anti-depressant marketed as Cymbalta by Eli Lilly, and

pregabalin, also marketed by Pfizer as Lyrica, another anti-depressant.
Neurontin recently lost its patent protection in the United States, and a number of generic versions are now available.

Most of these drugs need to be taken four times a day, opening a space for a pharmaceutical that requires less from the patient.

"Patients with neuropathic pain usually require several upward titrations of their pain medications before adequate pain control is achieved," said Clare Churchill, a healthcare analyst for Datamonitor, in the company's statement. "This can be particularly difficult if the patient must go through a difficult administration method a number of times before any results are seen."

Because many neuropathic-pain patients also are being treated for other conditions -- and therefore already must endure challenging pharmaceutical regimens -- Churchill said medication that could be taken orally once a day and would not negatively interact with other drugs would be ideal.

Datamonitor reported there are at least 97 compounds in development for the treatment of neuropathic pain, making it one of the most active pipelines in the central nervous system area. The company's analysis showed competition is centered on improved dosing formulations, but any serious drug would need to be at least equivalent in safety and efficacy to gabapentin and would need to demonstrate proven pain-reduction ability of greater than 50 percent in a significant majority of patients.

Dr. Michael Ferrante, director of the Pain and Spine Care Center at the UCLA Medical Center in Los Angeles, said he would be delighted to see new pharmaceuticals developed for neuropathic pain in the near future.

"Neurontin was a great step forward because it had a low side-effect profile and produced very quick results," Ferrante told United Press International. "Cymbalta, the newest medication, is more effective, but carries a significant risk of nausea. Lyrica is five times as effective as Neurontin, with a similar low side-effect profile, but is listed as a scheduled medication because it can potentially cause euphoria."

Ferrante said there is a strong need for an effective drug against neuropathic pain that has a low risk of side effects.

"People have been suffering for years with neuropathic pain, which is terribly debilitating," he said. "We need a home run for them."

Churchill said pharmaceutical companies also should consider devoting time and money to explore the pain-drug market in Japan, where neuropathic pain currently is treated with nerve blocks and vitamin B alone.

"Educating Japanese physicians on the use of the few current medications for neuropathic pain will be expensive and challenging," she said, "but the company that can do this effectively will reap a huge reward. There are a lot of sales out there."

http://biopsychiatry.com/bigpharma/neuropathic.html

BL 7050 New Drug For Neuropathic Pain

Following on from yesterday's post, today's article from sciencedaily.com (see link below) goes into more detail about the potassium-based neuropathy drug (at the moment, charmingly named, BL-7050) developed in Israel. It is still in the trials and testing stage, so won't be appearing on your pharmacist's shelves for some time yet but it sounds promising. The reason for posting two similar stories after each other, is to give a little more weight to the subject. The more serious websites devote attention to new drugs, the more they are likely to be real prospects of progress.

A New Drug to Manage Resistant Chronic Pain

ScienceDaily (Apr. 30, 2012)

Neuropathic pain, caused by nerve or tissue damage, is the culprit behind many cases of chronic pain. It can be the result of an accident or caused by a variety of medical conditions and diseases such as tumors, lupus, and diabetes. Typically resistant to common types of pain management including ibuprofen and even morphine, neuropathic pain can lead to lifelong disability for many sufferers.

Now a drug developed by Tel Aviv University researchers, known as BL-7050, is offering new hope to patients with neuropathic pain. Developed by Prof. Bernard Attali and Dr. Asher Peretz of TAU's Department of Physiology and Pharmacology at the Sackler Faculty of Medicine, the medication inhibits the transmission of pain signals throughout the body. In both in-vitro and in-vivo experiments measuring electrical activity of neurons, the compound has been shown to prevent the hyper-excitability of neurons -- protecting not only against neuropathic pain, but epileptic seizures as well.

The medication has been licensed by Ramot, TAU's technology transfer company, for development and commercialization by BioLineRx, an Israeli biopharmaceutical development company.

Targeting potassium for pain control

According to Prof. Attali, the medication works by targeting a group of proteins which act as a channel for potassium. Potassium has a crucial role in the excitability of cells, specifically those in the nervous system and the heart. When potassium channels don't function properly, cells are prone to hyper-excitability, leading to neurological and cardiovascular disorders such as epilepsy and arrhythmias. These are also the channels that convey pain signals caused by nerve or tissue damage, known as neuropathic pain.

With few treatment options available for neuropathic pain, Prof. Attali set out to develop a medication that could bind to and stabilize the body's potassium channels, controlling their hyper-excitability and preventing the occurrence of pain by keeping the channels open for the outflow of potassium. This novel targeting approach has been recently reported in the journal PNAS.

Inducing calm in the neurons

Understanding the mechanism that controls these channels has been crucial to the development of the drug. By successfully controlling the excitability of the neurons, Prof. Attali believes that BL-7050 could bring relief to hundreds of millions of patients around the world who suffer from neuropathic pain. The medication will reach the first phase of clinical trials in the near future.

In pre-clinical trials, BL-7050 was tested in rats experiencing both epilepsy and neuropathic pain and was found to be efficient in protecting against both when taken as a pill. While on the medication, rats were no longer affected by stimuli that had previously caused pain. Measures in the electrical activities of neurons also revealed that the medication was able to induce "calm" in the neurons, inhibiting pain pathways.

The above story is reprinted from materials provided by American Friends of Tel Aviv University.
http://www.sciencedaily.com/releases/2012/04/120430124715.htm

POMEGRANATE DRUG TO AID ALZHEIMERS PARKINSONS DISEASE

Dr Olumayokun Olajide's research will look to produce compound derivatives of punicalagin for a drug that would treat neuro-inflammation and slow down the progression of Alzheimer's disease

The onset of Alzheimer's disease can be slowed and some of its symptoms curbed by a natural compound that is found in pomegranate. Also, the painful inflammation that accompanies illnesses such as rheumatoid arthritis and Parkinson's disease could be reduced, according to the findings of a two-year project headed by University of Huddersfield scientist Dr Olumayokun Olajide, who specialises in the anti-inflammatory properties of natural products.

Now, a new phase of research can explore the development of drugs that will stem the development of dementias such as Alzheimer's, which affects some 800,000 people in the UK, with 163,000 new cases a year being diagnosed. Globally, there are at least 44.4 million dementia sufferers, with the numbers expected to soar.

The key breakthrough by Dr Olajide and his co-researchers is to demonstrate that punicalagin, which is a polyphenol -- a form of chemical compound -- found in pomegranate fruit, can inhibit inflammation in specialised brain cells known as micrologia. This inflammation leads to the destruction of more and more brain cells, making the condition of Alzheimer's sufferers progressively worse.

There is still no cure for the disease, but the punicalagin in pomegranate could prevent it or slow down its development.

Dr Olajide worked with co-researchers -- including four PhD students -- in the University of Huddersfield's Department of Pharmacy and with scientists at the University of Freiburg in Germany. The team used brain cells isolated from rats in order to test their findings. Now the research is published in the latest edition of the journalMolecular Nutrition & Food Research and Dr Olajide will start to disseminate his findings at academic conferences.

He is still working on the amounts of pomegranate that are required, in order to be effective.

"But we do know that regular intake and regular consumption of pomegranate has a lot of health benefits -- including prevention of neuro-inflammation related to dementia," he says, recommending juice products that are 100 per cent pomegranate, meaning that approximately 3.4 per cent will be punicalagin, the compound that slows down the progression of dementia.

Dr Olajide states that most of the anti-oxidant compounds are found in the outer skin of the pomegranate, not in the soft part of the fruit. And he adds that although this has yet to be scientifically evaluated, pomegranate will be useful in any condition for which inflammation -- not just neuro-inflammation -- is a factor, such as rheumatoid arthritis, Parkinson's and cancer.

The research continues and now Dr Olajide is collaborating with his University of Huddersfield colleague, the organic chemist Dr Karl Hemming. They will attempt to produce compound derivatives of punicalagin that could the basis of new, orally administered drugs that would treat neuro-inflammation.

Dr Olajide has been a Senior Lecturer at the University of Huddersfield for four years. His academic career includes a post as a Humboldt Postdoctoral Research Fellow at the Centre for Drug Research at the University of Munich. His PhD was awarded from the University of Ibadan in his native Nigeria, after an investigation of the anti-inflammatory properties of natural products.

He attributes this area of research to his upbringing. "African mothers normally treat sick children with natural substances such as herbs. My mum certainly used a lot of those substances. And then I went on to study pharmacology!"

Neuropathy Drug Research fails!

One of the much-trumpeted and supposedly most promising, gene therapy treatments, for neuropathic problems, called SB-509, has been abandoned by the company involved. It's some consolation that they're now concentrating solely on HIV therapies. The company involved, (Sangam) has suffered a significant drop in its share value but for us, it's just too depressing. Hopefully other companies will continue, or resume the search for an effective treatment for neuropathy. Link to article below.

Sangamo Fails Diabetic Neuropathy Study, Falls Back on HIV, Other Programs
by Luke Timmerman 10/3/11

Sangamo Biosciences’ lead drug candidate has flunked its biggest test yet in clinical trials, and the company said this morning that it’s time to move on to other programs.

The Richmond, CA-based company (NASDAQ: SGMO) said today that SB-509 failed in a study of 170 patients that randomly assigned patients with diabetic neuropathy to a new drug or a placebo. The company has now decided to scrap development of this particular drug, and will put more emphasis on its experimental treatments for HIV and single gene disorders.

Shares of Sangamo fell 22 percent to $3.38 shortly after the opening of trading this morning.

There wasn’t any sugarcoating of the results. Sangamo’s drug missed its primary and secondary goals, in which it was seeking to help diabetes patients fight one of the most common complications of the disease—numbness and tingling of nerves in the extremities. “We are disappointed,” said Edward Lanphier, Sangamo’s president and CEO, in a statement.

Sangamo’s study has been watched by scientists because of its potential for treating disease in a new way, through its zinc-finger protein technology. The technology is used to turn specific genes on or off in all kinds of living organisms, and one of the obvious applications is to turn off disease related genes in humans. Sangamo has shown some interesting results recently with a new treatment against HIV, and for a certain kind of hemophilia, but both programs are at earlier stages of development. Sangamo, which went public in 2000, has no drugs of its own on the market.

http://www.xconomy.com/san-francisco/2011/10/03/sangamo-fails-diabetic-neuropathy-study-falls-back-on-hiv-other-programs/

UNSUNG CELLS DOUBLE BENEFITS OF ANEW OSTEOPOROSIS DRUG

 Experiments in mice with a bone disorder similar to that in women after menopause show that a scientifically overlooked group of cells are likely crucial to the process of bone loss caused by the disorder, according to Johns Hopkins researchers. Their discovery, they say, not only raises the research profile of the cells, called preosteoclasts, but also explains the success and activity of an experimental osteoporosis drug with promising results in phase III clinical trials

A summary of their work will be published on Oct. 5 in the journal Nature Medicine.

"We didn't know that the drug affects preosteoclasts, nor did we understand how important preosteoclasts are in maintaining healthy bones," says Xu Cao, Ph.D., the Lee H. Riley Jr., M.D., Professor of Orthopaedic Surgery. "Now drug companies hoping to reverse osteoporosis can look for even more drugs that make use of and target these interesting cells."

The bones of mice, people and all land animals are not only necessary for strength and structure, but also as warehouses for calcium, which cells throughout the body use continuously for everyday tasks like cell-to-cell communication, muscle strength, and even embryo fertilization and hormone balance.

Calcium is taken from digested food and stored in the semihollow space inside bones. To access the stored calcium, the inner bone goes through a process called resorption, in which cells called osteoclasts attach to the bone and dissolve the calcium and other stored minerals. Nearby, specialized blood vessels pick up the calcium and send it throughout the body. They also bring in nutrients needed for new bone formation.

Under normal conditions, bone resorption is carefully balanced with bone rebuilding to maintain bone strength. But in women who have entered menopause, decreases in estrogen can cause bone resorption to overcome bone rebuilding, leading to osteoporosis and frequent bone breaks. In the U.S., an estimated 25 million women have osteoporosis.

"Most osteoporosis drugs on the market slow down bone resorption but do nothing to encourage bone rebuilding," says Cao. Previous data, including that from early clinical trials in humans, indicated that the drug odanacatib decreases bone resorption by hobbling CTSK, one of the enzymes used to resorb bone. What came as a pleasant surprise was that the same drug also increased bone rebuilding, but the question was how it did so, Cao says.

To learn more, Cao and his team studied mice genetically engineered to have neither bone-dissolving osteoclasts nor their precursors, preosteoclasts. Though the inner bones of the mice were abnormal, as expected, the team also found that the outside layers of the bones were thin. Moreover, the specialized blood vessels needed to transport bone-building supplies were in scarce supply, suggesting overall that osteoclasts and their precursors regulate bone building and bone resorption.

The team grew the two cell types separately in the laboratory and collected the liquid around them to test for proteins released by the cells. They found that preosteoclasts -- but not mature osteoclasts -- secrete a protein called PDGF-BB, which is a powerful attracter both of cells that make bone-building cells and those that make the specialized blood vessels. As expected, when the preosteoclasts of mice were prevented from making PDGF-BB, the mice had weak bones.

"Before a new building is constructed, the roads have to be in place so that the materials and equipment can be brought in," says Cao. "In a similar way, preosteoclasts call blood vessels into an area before bone-building cells begin to make new bone."

When mice were given L-235, the animal form of odanacatib, the numbers of their preosteoclasts and osteoclasts increased, and they secreted more PDGF-BB. The increased PDGF-BB brought in more cells for making blood vessels and bone, which led to more of the specialized blood vessels and thicker bones.

To see if the drug could help reverse the increased bone resorption and decreased blood vessel formation of postmenopausal osteoporosis, the researchers simulated menopause in female mice by removing their ovaries. At first, the mice had thinner bones and fewer blood vessels, but treatment with the drug increased the concentration of PDGF-BB in the blood, the number of specialized blood vessels both inside and outside of the bones, and the overall thickness and density of the bone.

According to Cao, in addition to slowing bone resorption by blocking CTSK, an osteoclast "weapon," the drug also appears to slow down the maturation of preosteoclasts, lengthening the amount of time they secrete PDGF-BB before becoming osteoclasts. With increased PDGF-BB, more specialized blood vessels are made and more bone-building cells arrive, restoring the balance between bone resorption and bone rebuilding.

Odanacatib is produced by Merck & Co. Inc. and has already gone through phase III clinical trials with good results, according to Cao. "It is unusual to see a single drug that decreases bone resorption and increases bone rebuilding at the same time," says Cao. "Beyond that, we now know just how important preosteoclasts and PDGF-BB are to bone building, which is information we can use in designing future studies."

HIGHLY EFFECTIVE NEW ANTI CANCER DRUG SHOWS FEW SIDE EFFECTS IN MICE

A new drug, known as OTS964, can eradicate aggressive human lung cancers transplanted into mice, according to a report in Science Translational Medicine. The drug, given as a pill or by injection, inhibits the action of a protein that is overproduced by several tumor types, including lung and breast, but is rarely expressed in healthy adult tissues. Without this protein, cancer cells fail to complete the cell-division process and die.

When taken by mouth, the drug was well tolerated with limited toxicity. An intravenous form, delivered within a liposome, was just as effective with fewer side effects. Both approaches -- described in the October 22, 2014 issue of Science Translational Medicine -- led to complete regression of transplanted tumors.

"We identified the molecular target for this drug ten years ago, but it took us nearly a decade to find an effective way to inhibit it," said study author Yusuke Nakamura, MD, PhD, professor of medicine at the University of Chicago and deputy director of the University's Center for Personalized Therapeutics. "We initially screened 300,000 compounds and then synthesized more than 1,000 of them, and found a few that were likely to work in humans. We focused on the most effective. We think we now have something very promising."

OTS964 targets TOPK (T -- lymphokine-activated killer cell -- originated protein kinase), a protein that is produced by a wide range of human cancers and is believed to promote tumor growth. High TOPK expression correlates with poor prognosis in patients with breast and lung cancer.

Initial studies of the drug, and a precursor called OTS514, found they were effective in killing cancer cells. But they could disrupt the production of new red and white blood cells, causing hematopoietic toxicity such as mild anemia and increasing the risk of infection. At the same time, the drugs increased the production of platelets, which help in blood clotting.

When the researchers encapsulated the drugs in liposomes -- microscopic bubbles similar to a cell membrane, commonly used to transport drugs within the body -- the drug no longer caused this decrease in red and white blood cells. This approach "completely eliminated the hematopoietic toxicity," the researchers wrote.

They tested OTS964 alone and in liposomes in mice with a highly aggressive human lung tumor known as LU-99. They allowed the tumors to grow to 150 cubic millimeters -- about the size of a raisin -- and then administered the drug intravenously to six mice, twice a week for three weeks. The tumors shrank rapidly and continued to shrink even after treatment stopped. In five of the six mice, the tumors completely disappeared -- three within 25 days of the first treatment and two within 29 days. Mice that received the liposome-coated drug had no detectable toxicity.

The drug also proved effective when taken in larger doses by mouth. Six mice with LU-99 lung tumors were fed 100 milligrams per kilogram of OTS964 every day for two weeks. Again, continuous tumor shrinkage was observed after the final dose of the drug. In all six mice the tumors completely regressed. All of the mice had low white-blood-cell counts after treatment, but they recovered within two weeks.

Although this was a small study, the outcome was dramatic. Seeing these results was a "quite exciting moment," said Nakamura, who stepped down from his role as Director in the Japanese Government's Office of Medical Innovation to join the faculty at the University of Chicago in April 2012. "It is rare to see complete regression of tumors in a mouse model," he said. "Many drugs can repress the growth, but it is uncommon to see them eradicated. This has rarely been reported."

Similar studies of the drug's effects on tumor cells growing outside the body enabled the researchers to videotape the process as the cancer cells died. TOPK appears to play a central role late in cytokinesis, the final stage in cell division. Dividing cancer cells would begin to separate into two new cells, but were unable to fully disconnect, retaining an intercellular bridge.

"Without TOPK the cells can't seem to divide; they can't make the break," Nakamura said. "They can't complete the process. Instead they remain tethered by a tiny bridge. When that finally breaks apart, they can't close the membrane. Everything within the cells spills out, they suffer and then die."

TOPK may provide a good drug target for several types of cancer. This study involved primarily lung cancers, but the gene is frequently upregulated in breast, brain, liver, bladder and other solid tumors as well as certain types of leukemia. The researchers are working with oncologists at the University to begin a phase-1 clinical trial as soon as the fall of 2015.

BIO INSPIRED NANO COCOONS OFFER TARGETTED DRUG DELIVERY AGAINST CANCER CELLS

Biomedical engineering researchers have developed a drug delivery system consisting of nanoscale “cocoons” made of DNA that target cancer cells and trick the cells into absorbing the cocoon before unleashing anticancer drugs. The work was done by researchers at North Carolina State University and the University of North Carolina at Chapel Hill.

 

This drug delivery system is DNA-based, which means it is biocompatible and less toxic to patients than systems that use synthetic materials,” says Dr. Zhen Gu, senior author of a paper on the work and an assistant professor in the joint biomedical engineering program at NC State and UNC Chapel Hill.

“This technique also specifically targets cancer cells, can carry a large drug load and releases the drugs very quickly once inside the cancer cell,” Gu says.

“In addition, because we used self-assembling DNA techniques, it is relatively easy to manufacture,” says Wujin Sun, lead author of the paper and a Ph.D. student in Gu’s lab.

Each nano-cocoon is made of a single strand of DNA that self-assembles into what looks like a cocoon, or ball of yarn, that measures 150 nanometers across.

The core of the nano-cocoon contains the anticancer drug doxorubicin (DOX) and a protein called DNase. The DNase, an enzyme that would normally cut up the DNA cocoon, is coated in a thin polymer that traps the DNase like a sword in a sheath.

The surface of the nano-cocoon is studded with folic acid ligands. When the nano-cocoon encounters a cancer cell, the ligands bind the nano-cocoon to receptors on the surface of the cell – causing the cell to suck in the nano-cocoon.

Once inside the cancer cell, the cell’s acidic environment destroys the polymer sheath containing the DNase. Freed from its sheath, the DNase rapidly slices through the DNA cocoon, spilling DOX into the cancer cell and killing it.

“We’re preparing to launch preclinical testing now,” Gu says. “We’re very excited about this system and think it holds promise for delivering a variety of drugs targeting cancer and other diseases.”

The paper, “ Cocoon like self degradable DNA-Nanoclew for Anticancer drug delivery was published online Oct. 13 in the Journal of the American Chemical Society. Co-authors include Yue Lu, a Ph.D. student in Gu’s lab; Margaret Reiff, an undergraduate student in the joint biomedical engineering department; Tianyue Jiang, a Ph.D. student in the joint biomedical engineering department and at the China Pharmaceutical University; and Dr. Ran Mo, a former postdoctoral researcher in the joint biomedical engineering department now at the China Pharmaceutical University.

This research was supported by the North Carolina Translational and Clinical Sciences Institute under grant number 1UL1TR001111 and with funding from NC State and UNC Chapel Hill.

MS Drug To Treat Chemo Neuropathy

Today's post from sciencedaily.com (see link below) talks about the danger of chemotherapy drugs causing neuropathy but also looks at an option to address that threat by using a drug normally used for Multiple Sclerosis. Unfortunately, cancer is more common these days due partly to our increasing age and partly to unwise lifestyle choices. Chemotherapy remains the standard treatment for tumors and as a result, the number of people suffering from neuropathy as a side effect is also increasing exponentially. The chemotherapy drugs most likely to cause neuropathy come from the Taxanes family of drugs but unfortunately, these are also the most effective in treating the cancer. It's a bit of a Catch22 situation but hopefully, progress will be made with this MS option to counteract the threat.

Possible answer to chemo pain found in multiple sclerosis drug
Date: June 23, 2014 Source: Saint Louis University 

Summary:

Two discoveries have been described by researchers: a molecular pathway by which a painful chemotherapy side effect happens and a drug that may be able to stop it. "The chemotherapy drug paclitaxel is widely used to treat many forms of cancer, including breast, ovarian and lung cancers," said one researcher. "Though it is highly effective, the medication, like many other chemotherapy drugs, frequently is accompanied by a debilitating side effect called chemotherapy induced peripheral neuropathy, or CIPN."

In a recently published study in the Journal of Biological Chemistry, Saint Louis University professor of pharmacological and physiological sciences Daniela Salvemini, Ph.D. describes two discoveries: a molecular pathway by which a painful chemotherapy side effect happens and a drug that may be able to stop it.

"The chemotherapy drug paclitaxel is widely used to treat many forms of cancer, including breast, ovarian and lung cancers," said Salvemini. "Though it is highly effective, the medication, like many other chemotherapy drugs, frequently is accompanied by a debilitating side effect called chemotherapy induced peripheral neuropathy, or CIPN."

CIPN can appear as tingling or numbness in the hands and feet, shooting or burning pain in the limbs, or can feel like hot or cold temperature extremes. Symptoms may resolve within weeks or months of stopping the chemotherapy treatment or may last for years. In addition to causing patients suffering, CIPN is often a limiting factor when it comes to treatment.

Physicians estimate that CIPN can occur in 30 to 90 percent of patients treated with taxanes (the class of drugs that includes paclitaxel) and combination chemotherapies.

Salvemini and her colleagues studied paclitaxel, which also is known as Taxol, and discovered that the pain pathway (the series of interactions between molecular-level components) is dependent on activation of sphingosine 1-phosphate receptor subtype 1 (S1PR1) in the central nervous system by engaging a series of damaging neuro-inflammatory processes leading to pain. By inhibiting this molecule, they found that they could block and reverse paclitaxel-induced neuropathic pain without interfering with the drug's anticancer effects.

This finding is particularly encouraging because a drug that modulates S1PR1 is already on the market. A medication called FTY720 (Gilenya) is FDA-approved as a therapy for multiple sclerosis. When Salvemini tested this drug in her lab, she found that the S1PR1 modulator weakened the neuroinflammatory processes, which in turn blocked and reversed neuropathic pain without altering the anticancer properties of paclitaxel. Further, the beneficial effects of FTY720 were not restricted to paclitaxel but also extended to another chemotherapeutic agent, the platinum based drug oxaliplatin which is widely used for metastatic colon cancer and other gastrointestinal cancers.

While clinical trials will be necessary to determine the safety and efficacy of the drug in treating CIPN, researchers are hopeful that they may be able not only to relieve cancer patients of debilitating pain, but also save more lives by permitting the administration of larger, potentially more effective doses of chemotherapy drugs.

"We have identified a critical pathway by which CIPN develops and continues that can be targeted with a drug that is already FDA approved. This does not happen often," said Salvemini. "We need to capitalize on these findings and explore use of these agents in cancer pain patients to improve quality of life and potentially maximize anticancer efficacy as soon as possible."

Story Source:

The above story is based on materials provided by Saint Louis University. The original article was written by Carrie Bebermeyer. Note: Materials may be edited for content and length.

Journal Reference:
K. Janes, J. W. Little, C. Li, L. Bryant, C. Chen, Z. Chen, K. Kamocki, T. Doyle, A. Snider, E. Esposito, S. Cuzzocrea, E. Bieberich, L. Obeid, I. Petrache, G. Nicol, W. L. Neumann, D. Salvemini. The Development and Maintenance of Paclitaxel-Induced Neuropathic Pain Requires Activation of the Sphingosine 1-Phosphate Receptor Subtype 1. Journal of Biological Chemistry, 2014; DOI: 10.1074/jbc.M114.569574 

 http://www.sciencedaily.com/releases/2014/06/140623131335.htm