Gene Therapy Lessens Pain of Diabetic Neuropathy (VIDEO)

By Pat Anson, Editor

An experimental gene therapy reduces pain and other symptoms by over 50 percent in patients with diabetic peripheral neuropathy, according to a new study at Northwestern University.

Nearly 26 million people in the United States have diabetes and about half have some form of neuropathy, according to the American Diabetes Association.  Diabetic peripheral neuropathy (DPN) causes nerves to send out abnormal signals. Patients feel pain or loss of feeling in their toes, feet, legs, hands and arms. It may also include a persistent burning, tingling or prickling sensation. The condition can lead to injuries, chronic foot ulcers and even amputations.

Keith Wenckowski, who has type-one diabetes, says it felt “like walking on glass” when he walked barefoot in sand.   

Wenckowski and 83 other participants in the Northwestern study received two low doses of a non-viral gene therapy called VM202. They went to a clinic twice in a two-week period for a series of injections into their calf muscles and lower legs. Some received injections of a saline placebo, others a low dose of the therapy and others a higher dose.

"Those who received the therapy reported more than a 50 percent reduction in their symptoms and virtually no side effects," said Dr. Jack Kessler, lead author of the study. "Not only did it improve their pain, it also improved their ability to perceive a very, very light touch."

After three months, patients in the low-dose group experienced a significant reduction in pain compared to the placebo group. The effect persisted at six and nine months in the low-dose group.

"I can now go to a beach and walk on the sand without feeling like I am walking on glass," says Wenckowski, more than a year after receiving the therapy. "I am hoping the effects I am feeling do not cease."

VM202 contains the human hepatocyte growth factor (HGF) gene. Growth factor is a naturally occurring protein in the body that acts on nerve cell to keep them alive, healthy and functioning. Future studies will investigate if the therapy can actually regenerate damaged nerves and reverse the neuropathy.

Patients with the most extreme form of the DPN feel intense pain with a slight graze or touch. The pain can interfere with daily activities, sleep, mood and can diminish quality of life. Many drugs used to treat DPN, such as Neurontin and Lyrica, either don’t work or have unpleasant side effects.

"We are hoping that the treatment will increase the local production of hepatocyte growth factor to help regenerate nerves and grow new blood vessels and therefore reduce the pain," said Senda Ajroud-Driss, MD, an attending physician at Northwestern Memorial Hospital and an author of the study.

"We found that the patients who received the low dose had a better reduction in pain than the people who received the high dose or the placebo. Side effects were limited to injection site reaction."

The results of this Phase II, double-blind, placebo-controlled study are being published in the journal Annals of Clinical and Translation Neurology.A future, much larger Phase III study will soon be underway.

"Right now there is no medication that can reverse neuropathy," Kessler said. "Our goal is to develop a treatment. If we can show with more patients that this is a very real phenomenon, then we can show we have not only improved the symptoms of the disease, namely the pain, but we have actually improved function."

Spider Venom Could Take the Sting Out of Chronic Pain

By Pat Anson, Editor

Black widow spiders are well known for their dangerous, painful and sometimes even lethal bites. The venom of a female black widow is 15 times as toxic as a rattlesnake’s.

But that venom also contains an ingredient that could be developed into a new class of potent painkilllers.

Researchers in Australia have identified seven compounds in the venom of spiders that block the body's ability to send signals to the brain through what is called the pain pathway – also known as Nav 1.7 channels.

"A compound that blocks Nav 1.7 channels is of particular interest for us. Previous research shows indifference to pain among people who lack Nav 1.7 channels due to a naturally-occurring genetic mutation - so blocking these channels has the potential of turning off pain in people with normal pain pathways," said study leader Glenn King, PhD, of The University of Queensland's Institute for Molecular Bioscience.

King and his colleagues built a system that can rapidly analyze the protein molecules in spider venoms. They studied the venom of over 200 spider species and found that 40% of the venoms contained at least one compound that blocked human Nav 1.7 channels. Of the seven promising compounds identified so far, one is particularly potent and has a chemical structure that suggests it has a high level of chemical, thermal, and biological stability, which would be essential for administering in a new medicine.

"Untapping this natural source of new medicines brings a distinct hope of accelerating the development of a new class of painkillers that can help people who suffer from chronic pain that cannot be treated with current treatment options," said researcher Julie Kaae Klint, PhD.

Researchers have only scratched the surface. There are over 45,000 species of spiders, many of which kill their prey with venoms that contain hundreds - or even thousands - of protein molecules that block nerve activity.

"A conservative estimate indicates that there are nine million spider-venom peptides, and only 0.01% of this vast pharmacological landscape has been explored so far," says Klint.

The study is published in the British Journal of Pharmacology.

Researchers are also studying the potential of venom in cone snails for its potential for blocking pain signals in humans. German scientists at the Pharmaceutical Institute of the University of Bonn say one advantage of the peptides found in snail venom is that they decompose quickly and are unlikely to cause dependency.

A pharmaceutical drug derived from cone snail neurotoxins has already been developed and marketed under the brand name Prialt. The drug is injected in spinal cord fluid to treat severe pain caused by failed back surgery, injury, AIDS, and cancer.

Mornings Worst for Lower Back Pain

By Pat Anson, Editor

People who suffer from lower back pain are significantly more likely to feel their first aches and pains after waking up in the morning, according to researchers in Australia.

Their study, which was published in the journal Arthritis Care & Research, found a variety of physical and psychosocial triggers that increase the risk of low back pain. People engaged in manual tasks involving awkward positions are eight times more likely to suffer from back pain, while people who are distracted or fatigued during activities were about four times more likely.

"Understanding which risk factors contribute to back pain and controlling exposure to these risks is an important first step in prevention," explains Manuela Ferreira, PhD, an associate professor at Sydney Medical School at The University of Sydney in New South Wales, Australia. "Our study is the first to examine brief exposure to a range of modifiable triggers for an acute episode of low back pain."

Researchers recruited nearly 1,000 participants from 300 primary care clinics in Sydney, Australia, who had acute low back pain. They were asked to self-report on a dozen physical or psychosocial factors in the 96 hours prior to the onset of their back pain.

The risk of a new episode of low back pain varied significantly depending on a range of triggers. Moderate to vigorous physical activity nearly tripled the risk of low back pain, while being distracted during an activity made participants 25 times more likely to have back pain.

Researchers recruited nearly 1,000 participants from 300 primary care clinics in Sydney, Australia, who had acute low back pain. They were asked to self-report on a dozen physical or psychosocial factors in the 96 hours prior to the onset of their back pain.

The risk of a new episode of low back pain varied significantly depending on a range of triggers. Moderate to vigorous physical activity nearly tripled the risk of low back pain, while being distracted during an activity made participants 25 times more likely to have back pain.

One finding not reported previously was that back pain risk was highest between 7:00 a.m. and noon. Ferreira believes that may be because people are not fully alert and discs in the spine may be more susceptible to damage in the morning.

One surprise finding is that growing older appears to moderate the risk of back pain caused by lifting heavy loads. The risk was 13.6 times higher for people at age 20. At age 40 it was 6.0 and at 60 years of age the risk was only 2.7 times higher.

Alcohol and sex appeared to have no association lower back pain.

"Understanding which modifiable risk factors lead to low back pain is an important step toward controlling a condition that affects so many worldwide," said Ferreira. "Our findings enhance knowledge of low back pain triggers and will assist the development of new prevention programs that can reduce suffering from this potentially disabling condition."

Lower back pain is the leading cause of disability worldwide, with nearly 10% of the world's population experiencing back pain at some point in their lives. Low back pain has a greater impact on global health than malaria, diabetes, or lung cancer; yet little progress has been made to identify effective prevention strategies.

Lower back pain is not usually linked to a serious disease. It can be triggered by everyday activities, including bad posture, bending awkwardly, lifting incorrectly or standing for long periods of time.

Study Finds Acupuncture Has Placebo Effect

By Pat Anson, Editor

When it comes to acupuncture, perception apparently does matter.

British researchers found in a new study that people with back pain who believe acupuncture will not help or do little to relieve their symptoms will gain less benefit from treatment than people who believe it works.

And people who feel they can manage their back pain have less disability as a result of acupuncture treatment.

“They experienced less disability over the course of treatment when they came to see their back pain as more controllable, when they felt they had better understanding of their back pain, when they felt better able to cope with it, were less emotional about it, and when they felt their back pain was going to have less of an impact on their lives," said Felicity Bishop, PhD, an Arthritis Research UK career development fellow.

Bishop and her colleagues at the University of Southampton wanted to find out why some people with back pain gain more benefit from acupuncture than others. They recruited 485 people with back pain and asked them to complete questionnaires before they saw an acupuncturist; as well as two weeks, three months and six months after starting treatment. The questions measured psychological factors, clinical and demographic characteristics, and back-related disability.

The study, which was funded by Arthritis Research UK, is being published in The Journal of Clinical Pain.

"The analysis showed that psychological factors were consistently associated with back-related disability," said Bishop, who believes acupuncturists should consider helping patients think more positively about their back pain as part of their treatment.

"People who started out with very low expectations of acupuncture -- who thought it probably would not help them -- were more likely to report less benefit as treatment went on,” she said.

Previous research has shown that many factors -- other than the insertion of needles – can play a role in the effectiveness of acupuncture, such as the relationship that the patient develops with the acupuncturist and the patient's belief about acupuncture.

"This study emphasises the influence of the placebo effect on pain. The process whereby the brain's processing of different emotions in relation to their treatment can influence outcome is a really important area for research,” said Dr. Stephen Simpson, director of research at Arthritis Research UK.

Acupuncture, which was originally developed as part of traditional Chinese medicine, is one of the most widely practiced forms of alternative medicine. As many as 3 million Americans receive acupuncture treatments, most often for relief of chronic pain.

While there is little consensus in the medical community about acupuncture’s value, a study in the Archives of Internal Medicine found that relief offered by acupuncture is real and should be considered a viable form of treatment .

Focusing on patients who reported chronic back and neck pain, osteoarthritis, chronic headache and shoulder pain, researchers at Memorial Sloan-Kettering Cancer Center in New York conducted a meta-analysis (a study of studies) of 29 studies involving nearly 18,000 adults.

“Acupuncture is effective for the treatment of chronic pain and is therefore a reasonable referral option. Significant differences between true and sham acupuncture indicate that acupuncture is more than a placebo,” the study concluded. “However, these differences are relatively modest, suggesting that factors in addition to the specific effects of needling are important contributors to the therapeutic effects of acupuncture.