IS THERE AN EFFECTIVE TREATMENT FOR EBOLA

A leading U.S. Ebola researcher from the University of Texas Medical Branch at Galveston has gone on record stating that a blend of three monoclonal antibodies can completely protect monkeys against a lethal dose of Ebola virus up to 5 days after infection, at a time when the disease is severe.

Thomas Geisbert, professor of microbiology and immunology, has written an editorial for Naturediscussing advances in Ebola treatment research. The filoviruses known as Ebola virus and Marburg virus are among the most deadly of pathogens, with fatality rates of up to 90 percent.

Since the discovery of Ebola in 1976, researchers have been actively working on treatments to combat infection. Studies over the past decade have uncovered three treatments that offer partial protection for monkeys against Ebola when given within an hour of virus exposure. One of these treatments, a VSV-based vaccine was used in 2009 to treat a laboratory worker in Germany shortly after she was accidentally stuck with a needle possibly contaminated by an Ebola-infected animal.

Further advances have been made that can completely protect monkeys against Ebola using small 'interfering' RNAs and various combinations of antibodies. But these treatments need to be given within two days of Ebola exposure.

"So although these approaches are highly important and can be used to treat known exposures, the need for treatments that can protect at later times after infection was paramount," said Geisbert.

Further research led to a cocktail of monoclonal antibodies that protected 43% of monkeys when given as late as five days after Ebola exposure, at a time when the clinical signs of the disease are showing.

The new study from Qui and colleagues at MAPP Biopharmaceutical Inc. used ZMAPP to treat monkeys given a lethal dose of Ebola. All of the animals survived and did not show any evidence of the virus in their systems 21 days after infection, even after receiving the treatment 5 days after infection. They also showed that ZMAPP inhibits replication of the Ebola virus in cell culture.

ZMAPP has been used to treat several patients on compassionate grounds. Of these, two US healthcare workers have recovered, although but whether ZMAPP had any effect is unknown, as 45% of patients in this outbreak survive without treatment. There were also two patients treated with ZMAPP who did not survive, but this may be because the treatment was started too late in the disease course.

"The diversity of strains and species of the Ebola and Marburg filoviruses is an obstacle for all candidate treatments," said Geisbert. "Treatments that may protect against one species of Ebola will probably not protect against a different species of the virus, and may not protect against a different strain within the species."

Although we certainly need treatments for filovirus infections, the most effective way to manage and control future outbreaks might be through vaccines, some of which have been designed to protect against multiple species and strains. During outbreaks, single-injection vaccines are needed to ensure rapid use and protection. At least five preventative vaccines have been reported to completely protect monkeys against Ebola and Marburg infection. But only the VSV-based vaccines have been shown to complete protect monkeys against Ebola after a single injection.

"Antibody therapies and several other strategies should be included in the arsenal of interventions for controlling future Ebola outbreaks," said Geisbert. "Although ZMAPP in particular has been administered for compassionate use, the next crucial step will be to formally assess its safety and effectiveness."

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.

Are Painkillers Through The Skin As Effective As Pills

Today's post from dailyrx.com (see link below) discusses whether topical creams and gels are as good as or better than analgesics in pill form. Many people find taking pills every day a difficult task and the rise in topical gel preparations provides a good alternative. The problem with topical gels and creams is that people have less trust in them than in a pill and have a tendency to over do the application, possibly leading to more of the drug being absorbed than is necessary. People living with neuropathy have long known about certain creams and patches which are meant to help with neuropathic symptoms but they too are not without controversy. Capsaicin cream and high strength patches can be painful and even cause burning and although many people have gained benefit from them, equally as many haven't. Because most people have symptoms in their feet and legs (or hands and arms), the topical creams can be applied at the source of the pain but the source of peripheral neuropathy pain can actually be elsewhere (in the spine or brain for instance); it's just the symptoms manifest themselves most commonly at the ends of nerve pathways (feet and hands). It's always advisable to get the best medical advice possible and ask to be monitored as to how these creams are working but with advances in preparations, they may well turn out to be effective alternatives to popping pills in the future.

Creams Versus Pills for Pain
Author Info: Charles E. Argoff, MD, of the Department of Neurology at Albany Medical College, Reviewed by: Joseph V. Madia, MD By:Laura Dobberstein March 2013


Pain relievers applied to the skin can be just as effective as those taken orally
(dailyRx News) Gel and cream pain relievers are gaining in popularity. This method of pain relief has fewer side effects than their pill counterparts and may work just as well.

A recent review looked at the use of pain relievers absorbed through the skin to manage pain.

The review found that the pain relieving medications diclofenac and ibuprofen were effective in treating muscle, tendon and ligaments and joint conditions like osteoarthritis when absorbed through the skin.

The medication lidocaine also effectively treated nerve-related pain when applied to the skin.
"Ask your doctor if topical analgesics are best."

Charles E. Argoff, MD, of the Department of Neurology at Albany Medical College, searched existing databases for studies on topical analgesics (pain relievers absorbed through the skin). Dr. Argoff identified a total of 65 studies that associated long-term, short-term and neuropathic pain with topical analgesics.

Neuropathic pain is a type of pain caused by nerve damage and often seen in patients with trauma, diabetes and amputations.

The most common drugs included in the studies were nonsteroidal anti-inflammatory drugs (NSAIDs) including diclofenac, ibuprofen, ketoprofen, piroxicam and indomethacin. The next most common drugs were lidocaine, capsaicin, amitriptyline, glyceryl trinitrate, opioids, menthol, pimecrolimus and phenytoin.

Eighteen of the studies used the pain relievers for short-term soft tissue injuries, 17 studies involved neuropathic pain and six involved pain induced for the purpose of the experiment only. Five of the studies used the pain relievers for long-term joint related conditions, five involved skin or leg ulcers and two used the medication for chronic knee pain.

Dr. Argoff concluded ibuprofen relieved chronic knee pain and short-term soft tissue injuries pain just as effectively when applied to the skin as when ingested.

The use of diclofenac topically to treat joint pain was shown in a study of temporomandibular joint disorder, a painful condition of the jaw. The study showed diclofenac applied to the skin worked just as well as when taken orally.

Lidocaine was the only drug in the studies that effectively relieved neuropathic pain.

No other drugs included in the review showed strong evidence of relief when used topically.

Pain relievers applied through the skin had fewer side effects, such as stomach and heart irritation, than orally administered pain relievers.

Dr. Argoff recommended the further study of NSAIDs and lidocaine for short-term and long-term pain relief.

The study was published in Mayo Clinic Proceedings.

Financial support for the study was provided by Mallinckrodt Inc., a company that manufactures pharmaceuticals and other health-related items.

Dr. Argoff is associated with over a dozen pharmaceutical companies and health research groups.

http://www.dailyrx.com/pain-relievers-applied-skin-can-be-just-effective-those-taken-orally

Just How Effective Are Opioids In Neuropathy Treatment

Today's post from medpagetoday.com (see link below) is an interesting review of a large-scale study of the effects of opioid treatment on people with neuropathy. It concludes that opioid use has its limitations but there is no evidence that it is either, over-prescribed by doctors, or abused by patients. This removes it immediately from the current hysteria concerning opioid medication and recognises that people with severe neuropathy have very few options. As a result, it calls for new medication development, not to remove the 'evils' of opioids but to provide a better alternative for patients in chronic pain. Definitely worth a read though maybe a little disheartening for people who rely on opioids to dampen their symptoms, having already exhausted all other options.

Long-Term Opioids May Not Help in Polyneuropathy
by Kristin Jenkins Contributing Writer, MedPage Today May 23, 2017 Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner last updated 05.23.2017
 
Action Points

Long-term opioid therapy among patients with polyneuropathy appears to increase the risk of adverse outcomes without benefiting functional status, according to a retrospective population-based study.
Note the data agree with prior studies showing opioid use disorders are more prevalent among those receiving long-term opioid therapy, but did not indicate that long-term opioid therapy significantly increases mortality among patients with polyneuropathy as it does among broader populations of patients reported elsewhere.


Long-term opioid therapy in patients with polyneuropathy appears to increase the risk of adverse outcomes without benefiting functional status, researchers said.

Data from a retrospective, population-based cohort study showed that 18.8% of 2,892 patients with polyneuropathy received opioids continuously for at least 90 days compared to 5.4% of 14,435 controls. They were also more likely to rely on gait aids and have difficulty climbing stairs (adjusted HR 1.7) and experience depression (adjusted HR 1.53), opioid dependence (aHR 2.85), and opioid overdose (aHR 5.12) compared to controls, Christopher J. Klein, MD, of the Mayo Clinic in Rochester, Minn, and colleagues reported online in JAMA Neurology.

"By showing that polyneuropathy increases the risk of long-term opioid therapy and that long-term opioid therapy is not associated with improved functional status but is associated with adverse outcomes, this study provides useful information to counsel patients with polyneuropathy who are considering or are already receiving opioid therapy," the researchers said. "Furthermore, it provides evidence that could influence treatment guidelines and health policy."

The researchers also reported that a diagnosis of opioid abuse among patients with polyneuropathy who were taking opioids for any length of time was observed in less than 2% of patients and that there was no significant association with overall mortality. However, there was a 7.2% rate of opioid dependence and a 2.6% rate of opioid overdose, they pointed out, adding that this "underscores that abuse and dependence are not synonymous."

"Thus, our results agree with those of prior studies citing that opioid use disorders are more prevalent among those receiving long-term opioid therapy, but we did not find that long-term opioid therapy significantly increases mortality among patients with polyneuropathy as it does among broader populations of patients reported elsewhere.

Importantly, the study also showed that neurologists and pain physicians were only prescribing long-term opioid therapy in a small percentage of patients, a finding consistent with national trends, the researchers noted. "Therefore, it is likely that discussing potential benefits, as well as adverse outcomes, of long-term opioid therapy will fall to the primary care clinician," Klein and colleagues said.

For the study, the Rochester Epidemiology Project (REP) database was searched for prescriptions given to patients with polyneuropathy and for those given to controls in ambulatory practice. All data came from participants who resided in Olmsted County from Jan. 1, 2006, to Dec. 31, 2010 and were reported previously. The latest follow-up ended Nov. 25, 2016.

Patients with polyneuropathy receiving 90 days or more of opioid therapy were more likely to be female (57%) than those receiving short-term opioid therapy (P<0 .001="" 46="" 69="" age="" also="" although="" between="" br="" common="" commonly="" differences="" documented="" for="" groups="" in="" indication="" long-term="" median="" most="" musculoskeletal="" no="" of="" opioid="" oxycodone="" p="0.13)." pain="" patients="" polyneuropathy="" prescribed="" prescribing="" significant="" similar="" starting="" the="" therapy.="" there="" trends="" two="" versus="" were="" with="" xycontin="" years="">
Although rates of lower limb complications were comparable between the two groups, patients with polyneuropathy used non-opioid analgesics more often than controls.

In an accompanying editorial, Nora Volkow, MD, of the National Institute on Drug Abuse, and Walter Koroshetz, MD, of the National Institute of Neurologic Disorders and Stroke, noted that opioids in this study were prescribed more often for treatment of non-neuropathic indications. However, this finding doesn't change the evidence behind current guidelines advising against opioids as first-line treatment in most cases of neuropathic pain because of long-term safety concerns, they said.

The study also highlights the limited alternatives for managing chronic pain, and the urgent need to develop new medications, the editorialists said. Recent work in animal models demonstrate that innovative opioid peptides and biased opioid agonists may provide equivalent pain relief with less tolerance and fewer adverse effects while success with biologics for inhibiting pain at the its source may shift the focus to prevention, they said.

"In the meantime, structural changes in the healthcare system, including training of physicians in the screening and management of pain, as well as coverage by insurance of comprehensive pain management programs, are needed to ensure that patients receive the most effective treatments for their chronic pain conditions," Volkow and Koroshetz said.

Limitations of the study include the fact that it was based on prescription data without confirmation that prescriptions were filled or taken as intended.


This study was funded by the Mayo Foundation for Medical Education and Research, Mayo Clinic Center for Individualized Medicine, and the National Institutes of Health (NIH). The study authors disclosed no conflicts of interest. The editorialists disclosed no funding or conflicts of interest.

https://www.medpagetoday.com/neurology/painmanagement/65497

Cannabis Inhaler Effective For Neuropathy

Today's short post from norml.org (see link below) reinforces the widely held belief that cannabis can relieve neuropathic symptoms as effectively as almost anything else. In this case, the cannabinoids are delivered via an inhaler which removes the need to smoke joints laced with tobacco (with all its associate dangers). Whatever, your opinion of cannabis, there is little doubt regarding its medicinal qualities and if you find that pills are not really helping you in your fight against neuropathic pain, it may be worthwhile looking into this option and at least trying it out. There are many other articles here on the blog about cannabis and neuropathy (see alphabetical list to the right).

Study: Cannabis Inhaler Delivers Effective Relief To Neuropathy Patients
Thursday, 21 August 2014

Haifa, Israel: The administration of a single dose of whole-plant cannabis via a thermal-metered inhaler is effective and well tolerated among patients suffering from neuropathy (nerve pain), according to clinical trial data published online ahead of print in the Journal of Pain and Palliative Care Pharmacotherapy.

Israeli investigators assessed the efficacy of a novel, portable metered-dose cannabis inhaler in eight subjects diagnosed with chronic neuropathic pain. Researchers reported that the vaporizing device administered an efficient, consistent, and therapeutically effective dosage of cannabinoids to all participants.

They concluded, "This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a delta-9-THC pharmacokinetic profile with low inter-individual variation of (maximum drug/plasma concentrations), achieving pharmaceutical standards for inhaled drugs."

A series of clinical trials conducted by investigators affiliated with the Center for Medicinal Cannabis Research at the University of California, San Diego previously determined that the inhalation of whole-plant cannabis is efficacious in the treatment of various types of neuropathic pain.

For more information, please contact Paul Armentano, NORML Deputy Director, at: paul@norml.org. Full text of the study, "The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: A phase 1a study," will appear in the Journal of Pain and Palliative Care Pharmacotherapy.

http://norml.org/news/2014/08/21/study-cannabis-inhaler-delivers-effective-relief-to-neuropathy-patients