SCIENTISTS REVERT HUMAN STEM CELLS TO PRISTINE STATE

Researchers at EMBL-EBI have resolved a long-standing challenge in stem cell biology by successfully 'resetting' human pluripotent stem cells to a fully pristine state, at point of their greatest developmental potential. The study, published in Cell, involved scientists from the UK, Germany and Japan and was led jointly by EMBL-EBI and the University of Cambridge.

Embryonic stem (ES) cells, which originate in early development, are capable of differentiating into any type of cell. Until now, scientists have only been able to revert 'adult' human cells (for example, liver, lung or skin) into pluripotent stem cells with slightly different properties that predispose them to becoming cells of certain types. Authentic ES cells have only been derived from mice and rats.

"Reverting mouse cells to a completely 'blank slate' has become routine, but generating equivalent naïve human cell lines has proven far more challenging," says Dr Paul Bertone, Research Group Leader at EMBL-EBI and a senior author on the study. "Human pluripotent cells resemble a cell type that appears slightly later in mammalian development, after the embryo has implanted in the uterus."

At this point, subtle changes in gene expression begin to influence the cells, which are then considered 'primed' towards a particular lineage. Although pluripotent human cells can be cultured from in vitro fertilised (IVF) embryos, until now there have been no human cells comparable to those obtained from the mouse.

Wiping cell memory

"For years, it was thought that we could be missing the developmental window when naïve human cells could be captured, or that the right growth conditions hadn't been found," Paul explains. "But with the advent of iPS cell technologies, it should have been possible to drive specialised human cells back to an earlier state, regardless of their origin -- if that state existed in primates."

Taking a new approach, the scientists used reprogramming methods to express two different genes, NANOG and KLF2, which reset the cells. They then maintained the cells indefinitely by inhibiting specific biological pathways. The resulting cells are capable of differentiating into any adult cell type, and are genetically normal.

The experimental work was conducted hand-in-hand with computational analysis.

"We needed to understand where these cells lie in the spectrum of the human and mouse pluripotent cells that have already been produced," explains Paul. "We worked with the EMBL Genomics Core Facility to produce comprehensive transcriptional data for all the conditions we explored. We could then compare reset human cells to genuine mouse ES cells, and indeed we found they shared many similarities."

Together with Professor Wolf Reik at the Babraham Institute, the researchers also showed that DNA methylation (biochemical marks that influence gene expression) was erased over much of the genome, indicating that reset cells are not restricted in the cell types they can produce. In this more permissive state, the cells no longer retain the memory of their previous lineages and revert to a blank slate with unrestricted potential to become any adult cell.

Unlocking the potential of stem cell therapies

The research was performed in collaboration with Professor Austin Smith, Director of the Wellcome Trust-Medical Research Council Stem Cell Institute.

"Our findings suggest that it is possible to rewind the clock to achieve true ground-state pluripotency in human cells," said Professor Smith. "These cells may represent the real starting point for formation of tissues in the human embryo. We hope that in time they will allow us to unlock the fundamental biology of early development, which is impossible to study directly in people."

The discovery paves the way for the production of superior patient material for translational medicine. Reset cells mark a significant advance for human stem cell applications, such as drug screening of patient-specific cells, and are expected to provide reliable sources of specialised cell types for regenerative tissue grafts.

CHEMISTS RECRUIT ANTHRAX TO DELIVER CANCER CELLS

Bacillus anthracis bacteria have very efficient machinery for injecting toxic proteins into cells, leading to the potentially deadly infection known as anthrax. A team of MIT researchers has now hijacked that delivery system for a different purpose: administering cancer drugs.

"Anthrax toxin is a professional at delivering large enzymes into cells," says Bradley Pentelute, the Pfizer-Laubauch Career Development Assistant Professor of Chemistry at MIT. "We wondered if we could render anthrax toxin nontoxic, and use it as a platform to deliver antibody drugs into cells."

In a paper appearing in the journal ChemBioChem, Pentelute and colleagues showed that they could use this disarmed version of the anthrax toxin to deliver two proteins known as antibody mimics, which can kill cancer cells by disrupting specific proteins inside the cells. This is the first demonstration of effective delivery of antibody mimics into cells, which could allow researchers to develop new drugs for cancer and many other diseases, says Pentelute, the senior author of the paper.

Hitching a ride

Antibodies -- natural proteins the body produces to bind to foreign invaders -- are a rapidly growing area of pharmaceutical development. Inspired by natural protein interactions, scientists have designed new antibodies that can disrupt proteins such as the HER2 receptor, found on the surfaces of some cancer cells. The resulting drug, Herceptin, has been successfully used to treat breast tumors that overexpress the HER2 receptor.

Several antibody drugs have been developed to target other receptors found on cancer-cell surfaces. However, the potential usefulness of this approach has been limited by the fact that it is very difficult to get proteins inside cells. This means that many potential targets have been "undruggable," Pentelute says.

"Crossing the cell membrane is really challenging," he says. "One of the major bottlenecks in biotechnology is that there really doesn't exist a universal technology to deliver antibodies into cells."

For inspiration to solve this problem, Pentelute and his colleagues turned to nature. Scientists have been working for decades to understand how anthrax toxins get into cells; recently researchers have started exploring the possibility of mimicking this system to deliver small protein molecules as vaccines.

The anthrax toxin has three major components. One is a protein called protective antigen (PA), which binds to receptors called TEM8 and CMG2 that are found on most mammalian cells. Once PA attaches to the cell, it forms a docking site for two anthrax proteins called lethal factor (LF) and edema factor (EF). These proteins are pumped into the cell through a narrow pore and disrupt cellular processes, often resulting in the cell's death.

However, this system can be made harmless by removing the sections of the LF and EF proteins that are responsible for their toxic activities, leaving behind the sections that allow the proteins to penetrate cells. The MIT team then replaced the toxic regions with antibody mimics, allowing these cargo proteins to catch a ride into cells through the PA channel.

'A prominent advance'

The antibody mimics are based on protein scaffolds that are smaller than antibodies but still maintain structural diversity and can be designed to target different proteins inside a cell. In this study, the researchers successfully targeted several proteins, including Bcr-Abl, which causes chronic myeloid leukemia; cancer cells in which that protein was disrupted underwent programmed cell suicide. The researchers also successfully blocked hRaf-1, a protein that is overactive in many cancers.

"This work represents a prominent advance in the drug-delivery field," says Jennifer Cochran, an associate professor of bioengineering at Stanford University. "Given the efficient protein delivery Pentelute and colleagues achieved with this technology compared to a traditional cell-penetrating peptide, studies to translate these findings to in vivo disease models will be highly anticipated."

The MIT team is now testing this approach to treat tumors in mice and is also working on ways to deliver the antibodies to specific types of cells.

Using Gene Therapy To Relieve Neuropathic Pain

Today's post from newsmax.com (see link below) revisits a story reported earlier on this blog about the new non-viral gene-therapy called VM202, which can potentially reduce neuropathic pain in ways that standard medications currently can only dream of. To reiterate, the study showed that just two low doses of VM202 produced pain relief lasting for months, with the added bonus of no side effects. The article explains what VM202 is but doesn't tell us how widely it's used at the moment; whether it's still in the testing stages, or whether it's available to the main population of neuropathy patients. Maybe your area, or country is carrying out trials as you read this and maybe you can get onto those but until things are much clearer, the best you can do is discuss it with your doctor or neurologist and ensure that they are aware of both the option and the potential of this treatment.

New Gene Therapy Eases Diabetes-Related Pain
Thursday, 05 Mar 2015 By Nick Tate

Northwestern University geneticists have developed a promising new gene therapy technique that helps those who suffered from painful diabetic neuropathy (PDN).

The study, published in the journal Annals of Clinical and Translation Neurology, found that two low dose rounds of a non-viral gene therapy called VM202 greatly eased the pain in people with PDN and the relief lasted for months.

"Those who received the therapy reported more than a 50 percent reduction in their symptoms and virtually no side effects," said lead researcher Jack Kessler, a professor in the department of pharmacology at Northwestern University Feinberg School of Medicine and a physician at Northwestern Memorial Hospital. "Not only did it improve their pain, it also improved their ability to perceive a very, very light touch."

VM202 contains human hepatocyte growth factor (HGF) gene, a naturally occurring protein in the body that acts on nerve cells to keep them alive, healthy, and functioning.
 
Keith Wenckowski, one of the 84 participants in the study who suffers from PDN, said walking barefoot on sand "felt like walking on glass" because of the condition — forcing him to wear shoes, even to the beach.

But Wenckowski said the VM202 therapy significantly eased his pain.

"I can now go to a beach and walk on the sand without feeling like I am walking on glass," he said.

There is not existing treatment for PDN, which affects up to 25 percent of diabetics. Patients with the condition have abnormally high levels of glucose in their blood that can be toxic to vital organs, tissues, and nerve cells.

Painkillers and other medications can alleviate symptoms, but carry undesirable 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, M.D., associate professor in neurology at Feinberg and an attending physician at Northwestern Memorial Hospital.

"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."

© 2015 NewsmaxHealth. All rights reserved.

http://www.newsmax.com/Health/Health-News/gene-therapy-diabetes-neuropathy/2015/03/05/id/628524/

MDA7 To Inhibit Inflammation Causing Neuropathic Pain

When treatments only have letter and a number as a name, most people switch off before reading any further but today's post from consultqd.clevelandclinic.org (see link below) may be worth more attention from the casual reader. As a result of recent research into the sorts of inflammations that cause neuropathic pain, Cleveland Clinic investigators have synthesised a molecule that may inhibit the pathways that cause the inflammation. This molecule is called MDA7 and is a sort of synthetic cannabinoid. Dr. Naguib, who heads the team has high hopes for an eventual treatment based on this repression of microglial (15% of all nerve cells found in the brain) inflammation. At the moment, long-suffering rodents have been the recipients of this development but moves are underway for testing on humans. If you understand nothing else from this article, it's fascinating to learn that most of our neuropathic pain is caused by good old fashioned inflammation, which is a word most people will understand immediately. More hope for future generations.

Microglial Inflammation: A Promising Target in Neuropathic Pain Also Plays Role in Memory Deficiency
Pursuing a potentially treatable common pathway 
Feb. 2, 2015 
 
Promising research by Cleveland Clinic investigators demonstrates that microglial inflammation is a common pathway ‒ and a potentially treatable one ‒ for neuropathic pain and other treatment-resistant neuroinflammatory conditions, including Alzheimer disease (AD).

“Microglial inflammation is a mechanism of many CNS disorders ‒ neuropathic pain, AD, multiple sclerosis, parkinsonism, you name it,” says lead researcher Mohamed Naguib, MD, of Cleveland Clinic’s Anesthesiology Institute, which includes the Department of Pain Management.

His team has synthesized a molecule called MDA7, a cannabinoid type 2 (CB2) receptor-selective agonist, to inhibit microglial inflammation in hopes of effectively treating neuropathic pain and other conditions. “MDA7 prevents microglial activation and recruitment, which represent the elemental pathway of microglial inflammation,” explains Dr. Naguib. 

Efficacy in a Rodent Model of Chemo-Induced Neuropathic Pain

The researchers demonstrated as much in a 2012 paper in Anesthesia and Analgesia (2012;114[5]:1104-1120) reporting findings from a rodent model of paclitaxel-induced neuropathy, which is associated with activation of microglia followed by the activation and proliferation of astrocytes and the expression and release of pro-inflammatory cytokines. They found that MDA7 prevented paclitaxel-induced allodynia in rats and mice in a dose- and time-sensitive fashion without compromising paclitaxel’s anticancer effects. MDA7’s anti-allodynia effect was absent in CB2–/– mice and was countered by CB2 antagonists, which suggests it directly involves CB2 receptor activation.

Because all neuropathic pain shares the mechanism of microglial inflammation, Dr. Naguib expects the same effect in neuropathic pain types outside the chemotherapy setting. “We started with chemotherapy-induced neuropathy because it’s an area of unmet therapeutic need,” he says.

Similar Efficacy in CRPS

His team recently finished a study using a vascular occlusion model in the rat to replicate another form of chronic pain with a microglial inflammation mechanism, complex regional pain syndrome (CRPS). MDA7 was again highly effective, both at the molecular level and in terms of phenotypic response. They expect to submit the CRPS study for publication this year.

Promise for Alzheimer Disease

The wider biomedical community learned of the team’s work via an exciting study in February’s Nature Neuroscience (2014;17[2]:223-231) linking microglia-mediated inflammatory changes in a postsynaptic protein, neuroligin 1, to amyloid-associated memory deficiency in rodents.

Current models of AD hold that amyloid plaques accumulate in the brain, overwhelming the microglia that serve as the nervous system’s main form of active immune defense. When the microglia cannot clear out amyloid rapidly enough, they become inflamed, which leads to gene modifications in the brain.

“As our research into microglial inflammation advanced, it became clear how important this inflammation is to a variety of disease processes, which led down the Alzheimer path,” says Dr. Naguib.

His team’s Nature Neuroscience study showed that the microglial inflammation-induced gene changes in the brain include suppressed expression of the neuroligin 1 protein ‒ and that this suppression leads to hippocampal glutamatergic dysfunction and memory deficiency in rodents. The effects were ameliorated by inhibiting microglial activation. “These findings link neuroinflammation, synaptic efficacy and memory, thus providing insight into the pathogenesis of amyloid-associated diseases,” the researchers concluded.

Dr. Naguib notes that much research remains, but the findings suggest that MDA7 represents a promising new therapeutic approach to AD and other conditions involving microglia-mediated neuroinflammation, such as multiple sclerosis and Parkinson disease.

Next Steps

In the near term, the researchers are focused on gaining funding to move MDA7 into phase 1 human studies for chemotherapy-induced neuropathy, which they hope to begin by 2015. Studies of MDA7 in animal models of AD will take longer, due to the longitudinal nature of AD, but Dr. Naguib says the team is committed to pursuing that research as well.

Mohamed Naguib, MD is a professor of anesthesiology in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

Consult QD—Neurosciences

The neurosciences field is changing rapidly, and so are all of our practices. Join clinicians and researchers from Cleveland Clinic’s Neurological Institute in this open forum for discussion of the latest advances in patient care, research, and technology — specifically for healthcare professionals.

http://consultqd.clevelandclinic.org/2015/02/microglial-inflammation-a-promising-target-in-neuropathic-pain-also-plays-role-in-memory-deficiency/

NICOTINE WITHDRAWAL REDUCES RESPONSE TO REWARDS ACROSS SPECIES

Cigarette smoking is a leading cause of preventable death worldwide and is associated with approximately 440,000 deaths in the United States each year, according to the U.S. Centers for Disease Control and Prevention, but nearly 20 percent of the U.S. population continues to smoke cigarettes. While more than half of U.S. smokers try to quit every year, less than 10 percent are able to remain smoke-free, and relapse commonly occurs within 48 hours of smoking cessation. Learning about withdrawal and difficulty of quitting can lead to more effective treatments to help smokers quit.

In a first of its kind study on nicotine addiction, scientists measured a behavior that can be similarly quantified across species like humans and rats, the responses to rewards during nicotine withdrawal. Findings from this study were published online on Sept. 10, 2014 in JAMA Psychiatry.

Response to reward is the brain's ability to derive and recognize pleasure from natural things such as food, money and sex. The reduced ability to respond to rewards is a behavioral process associated with depression in humans. In prior studies of nicotine withdrawal, investigators used very different behavioral measurements across humans and rats, limiting our understanding of this important brain reward system.

Using a translational behavioral approach, Michele Pergadia, Ph.D., associate professor of clinical biomedical science in the Charles E. Schmidt College of Medicine at Florida Atlantic University, who completed the human study while at Washington University School of Medicine, Andre Der-Avakian, Ph.D., who completed the rat study at the University of California San Diego (UCSD), and colleagues, including senior collaborators Athina Markou, Ph.D. at UCSD and Diego Pizzagalli, Ph.D. at Harvard Medical School, found that nicotine withdrawal similarly reduced reward responsiveness in human smokers -- particularly those with a history of depression -- as well as in nicotine-treated rats.

Pergadia, one of the lead authors, notes that replication of experimental results across species is a major step forward, because it allows for greater generalizability and a more reliable means for identifying behavioral and neurobiological mechanisms that explain the complicated behavior of nicotine withdrawal in humans addicted to tobacco.

"The fact that the effect was similar across species using this translational task not only provides us with a ready framework to proceed with additional research to better understand the mechanisms underlying withdrawal of nicotine, and potentially new treatment development, but it also makes us feel more confident that we are actually studying the same behavior in humans and rats as the studies move forward," said Pergadia.

Pergadia and colleagues plan to pursue future studies that will include a systematic study of depression vulnerability as it relates to reward sensitivity, the course of withdrawal-related reward deficits, including effects on relapse to smoking, and identification of processes in the brain that lead to these behaviors.

Pergadia emphasizes that the ultimate goal of this line of research is to improve treatments that manage nicotine withdrawal-related symptoms and thereby increase success during efforts to quit.

"Many smokers are struggling to quit, and there is a real need to develop new strategies to aid them in this process. Therapies targeting this reward dysfunction during withdrawal may prove to be useful," said Pergadia.

PLUCK HAIR IN A SPECIFIC PATTERN TO GROW NEW HAIR

 

If  there's a cure for male pattern baldness, it might hurt a little. A team led by USC Stem Cell Principal Investigator Cheng-Ming Chuong has demonstrated that by plucking 200 hairs in a specific pattern and density, they can induce up to 1,200 replacement hairs to grow in a mouse. These results are published in the April 9 edition of the journal Cell.

It is a good example of how basic research can lead to a work with potential translational value," said Chuong, who is a professor of pathology at the Keck School of Medicine of USC. "The work leads to potential new targets for treating alopecia, a form of hair loss."

The study began a couple of years ago when first author and visiting scholar Chih-Chiang Chen arrived at USC from National Yang-Ming University and Veterans General Hospital, Taiwan. As a dermatologist, Chen knew that hair follicle injury affects its adjacent environment, and the Chuong lab had already established that this environment in turn can influence hair regeneration. Based on this combined knowledge, they reasoned that they might be able to use the environment to activate more follicles.

To test this concept, Chen devised an elegant strategy to pluck 200 hair follicles, one by one, in different configurations on the back of a mouse. When plucking the hairs in a low-density pattern from an area exceeding six millimeters in diameter, no hairs regenerated. However, higher-density plucking from circular areas with diameters between three and five millimeters triggered the regeneration of between 450 and 1,300 hairs, including ones outside of the plucked region.

Working with Arthur D. Lander from the University of California, Irvine, the team showed that this regenerative process relies on the principle of "quorum sensing," which defines how a system responds to stimuli that affect some, but not all members. In this case, quorum sensing underlies how the hair follicle system responds to the plucking of some, but not all hairs.

Through molecular analyses, the team showed that these plucked follicles signal distress by releasing inflammatory proteins, which recruit immune cells to rush to the site of the injury. These immune cells then secrete signaling molecules such as tumor necrosis factor alpha (TNF-α), which, at a certain concentration, communicate to both plucked and unplucked follicles that it's time to grow hair.

"The implication of the work is that parallel processes may also exist in the physiological or pathogenic processes of other organs, although they are not as easily observed as hair regeneration," said Chuong.

BENEFITS FOR BABIES EXPOSED TO TWO LANGUAGES

A team of investigators and clinician-scientists in Singapore and internationally have found that there are advantages associated with exposure to two languages in infancy. As part of a long-term birth cohort study of Singaporean mothers and their offspring called GUSTO -- seminally a tripartite project between A*STAR's Singapore Institute for Clinical Sciences (SICS), KK Women's and Children's Hospital (KKH) and the National University Hospital (NUH) -- (see Annex A), six-month old bilingualinfants recognised familiar images faster than those brought up in monolingual homes. They also paid more attention to novel images compared to monolingual infants.

The findings reveal a generalized cognitive advantage that emerges early in bilingual infants, and is not specific to a particular language. The findings were published online on 30 July 2014 in the scientific journal, Child Development.

Infants were shown a coloured image of either a bear or a wolf. For half the group, the bear was made to become the "familiar" image while the wolf was the "novel" one, and vice versa for the rest of the group. The study showed that bilingual babies got bored of familiar images faster than monolingual babies.

Several previous studies in the field have shown that the rate at which an infant becomes bored of a familiar image and subsequent preference for novelty is a common predictor of better pre-school developmental outcomes, such as advanced performance in concept formation, non-verbal cognition, expressive and receptive language, and IQ tests. The past studies showed that babies who looked at the image and then rapidly get bored, demonstrated higher performance in various domains of cognition and language later on as children.

Bilingual babies also stared for longer periods of time at the novel image than their monolingual counterparts, demonstrating "novelty preference." Other studies in the field have shown this is linked with improved performance in later IQ and vocabulary tests during pre-school and school-going years.

Associate Professor Leher Singh, who is from the Department of Psychology at the National University of Singapore's Faculty of Arts and Social Sciences and lead author of this study said, "One of the biggest challenges of infant research is data collection. Visual habituation works wonderfully because it only takes a few minutes and capitalises on what babies do so naturally, which is to rapidly become interested in something new and then rapidly move on to something else. Even though it is quite a simple task, visual habituation is one of the few tasks in infancy that has been shown to predict later cognitive development."

A bilingual infant encounters more novel linguistic information than its monolingual peers. A six-month old infant in a bilingual home is not just learning another language; it is learning two languages while learning to discern between the two languages it is hearing. It is possible that since learning two languages at once requires more information-processing efficiency, the infants have a chance to rise to this challenge by developing skills to cope with it.

Said Assoc Prof Leher Singh, "As adults, learning a second language can be painstaking and laborious. We sometimes project that difficulty onto our young babies, imagining a state of enormous confusion as two languages jostle for space in their little heads. However, a large number of studies have shown us that babies are uniquely well positioned to take on the challenges of bilingual acquisition and in fact, may benefit from this journey."

In comparison to many other countries, a large proportion of Singaporean children are born into bilingual environments. This finding that bilingual input to babies is associated with cognitive enhancement, suggests a potentially strong neurocognitive advantage for Singaporean children outside the domain of language, in processing new information and recognising familiar objects with greater accuracy.

Said Assoc Prof Chong Yap Seng, Lead Principal Investigator for GUSTO, "This is good news for Singaporeans who are making the effort to be bilingual. These findings were possible because of the unique Singaporean setting of the study and the detailed neurodevelopmental testing that the GUSTO researchers perform." Assoc Prof Chong is Senior Consultant, Department of Obstetrics & Gynaecology, National University Hospital (NUH), as well as Acting Executive Director, Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR).

SIMPLE METHOD TURNS HUMAN SKIN CELLS IN TO IMMUNE STRENGTHENING WHITE BLOOD CELLS

For the first time, scientists have turned human skin cells into transplantable white blood cells, soldiers of the immune system that fight infections and invaders. The work, done at the Salk Institute, could let researchers create therapies that introduce into the body new white blood cells capable of attacking diseased or cancerous cells or augmenting immune responses against other disorders

The work, as detailed in the journal Stem Cells, shows that only a bit of creative manipulation is needed to turn skin cells into human white blood cells.

"The process is quick and safe in mice," says senior author Juan Carlos Izpisua Belmonte, holder of Salk's Roger Guillemin Chair. "It circumvents long-standing obstacles that have plagued the reprogramming of human cells for therapeutic and regenerative purposes."

Those problems includes the long time -- at least two months -- and tedious laboratory work it takes to produce, characterize and differentiate induced pluripotent stem (iPS) cells, a method commonly used to grow new types of cells. Blood cells derived from iPS cells also have other obstacles: an inability to engraft into organs or bone marrow and a likelihood of developing tumors.

The new method takes just two weeks, does not produce tumors, and engrafts well.

"We tell skin cells to forget what they are and become what we tell them to be -- in this case, white blood cells," says one of the first authors and Salk researcher Ignacio Sancho-Martinez. "Only two biological molecules are needed to induce such cellular memory loss and to direct a new cell fate."

Belmonte's team developed the faster technique (called indirect lineage conversion) and previously demonstrated that these approaches could be used to produce human vascular cells, the ones that line blood vessels. Rather than reversing cells all the way back to a stem cell state before prompting them to turn into something else, such as in the case of iPS cells, the researchers "rewind" skin cells just enough to instruct them to form the more than 200 cell types that constitute the human body.

The technique demonstrated in this study uses a molecule called SOX2 to become somewhat plastic -- the stage of losing their "memory" of being a specific cell type. Then, researchers use a genetic factor called miRNA125b that tells the cells that they are actually white blood cells.

The researchers are now conducting toxicology studies and cell transplantation proof-of-concept studies in advance of potential preclinical and clinical studies.

"It is fair to say that the promise of stem cell transplantation is now closer to realization," Sancho-Martinez says.

Study co-authors include investigators from the Center of Regenerative Medicine in Barcelona, Spain, and the Centro de Investigacion Biomedica en Red de Enfermedades Raras in Madrid, Spain.

SCIENTISTS INVENT BIO SPLEEN DEVICE THAT USES MAGNET TO CLEANSE BLOOD

Scientists recently unveiled a device called 'bio-spleen,' which uses a magnet to cleanse the blood by bacteria, fungi and toxins.

Researchers hope that the external gadget, potentially throwing a lifeline to patients with sepsis and other infections, could be adapted one day for stripping Ebola and other viruses from blood, News24.com reported.

Acting rather like a spleen, the invention uses magnetic nanobeads coated with a genetically-engineered human blood protein called MBL.

Donald Ingber said that this treatment could be carried out even before the pathogen has been formally identified and the optimal antibiotic treatment has been chosen.

They could potentially treat patients with this bio-spleen during the most infectious, viraemic phase of the disease and reduce the amount of virus in their blood, he further added.

The device was developed to treat sepsis, or blood infection, which affects 18 million people in the world every year, with a 30 percent-50 percent mortality rate

HOW LEARNING TO TALK IS IN THE GENES

Researchers have found evidence that genetic factors may contribute to the development of language during infancy

Scientists from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol worked with colleagues around the world to discover a significant link between genetic changes near the ROBO2 gene and the number of words spoken by children in the early stages of language development.

Children produce words at about 10 to 15 months of age and our range of vocabulary expands as we grow -- from around 50 words at 15 to 18 months, 200 words at 18 to 30 months, 14,000 words at six-years-old and then over 50,000 words by the time we leave secondary school.

The researchers found the genetic link during the ages of 15 to 18 months when toddlers typically communicate with single words only before their linguistic skills advance to two-word combinations and more complex grammatical structures.

The results, published in Nature Communications today [16 Sept], shed further light on a specific genetic region on chromosome 3, which has been previously implicated in dyslexia and speech-related disorders.

The ROBO2 gene contains the instructions for making the ROBO2 protein. This protein directs chemicals in brain cells and other neuronal cell formations that may help infants to develop language but also to produce sounds.

The ROBO2 protein also closely interacts with other ROBO proteins that have previously been linked to problems with reading and the storage of speech sounds.

Dr Beate St Pourcain, who jointly led the research with Professor Davey Smith at the MRC Integrative Epidemiology Unit, said: "This research helps us to better understand the genetic factors which may be involved in the early language development in healthy children, particularly at a time when children speak with single words only, and strengthens the link between ROBO proteins and a variety of linguistic skills in humans."

Dr Claire Haworth, one of the lead authors, based at the University of Warwick, commented: "In this study we found that results using DNA confirm those we get from twin studies about the importance of genetic influences for language development. This is good news as it means that current DNA-based investigations can be used to detect most of the genetic factors that contribute to these early language skills."

The study was carried out by an international team of scientists from the EArly Genetics and Lifecourse Epidemiology Consortium (EAGLE) and involved data from over 10,000 children.

Stop Searching For A Nerve Pain Cure And Begin Learning To Live With It

Today's interesting post from healthskills.wordpress.com (see link below) is an impassioned and intelligently written plea for doctors to start aiming their treatment (at least partially) at learning to live with pain instead of constantly trying to 'cure' it with chemicals. Now nobody knows better than the average neuropathy patient, that chemical treatments almost never take neurological pain away completely. We're well aware that the pills we take are doing nothing to improve our nerve damage and at best provide a sort of security blanket that masks the pain. That security blanket then becomes something we rely on to get us through the day but its side effects can severely affect our well-being and sense of self. Pain is an experience not a disease. Pain is just pain and doesn't mean that the problem is getting worse, so why can't we learn better to accept it for what it is and manage it in such a way that it becomes part of our daily lives. Stop trawling through drug lists in the search for pain reduction and begin learning to manage it. That begins by accepting that the pain is there; every day and maybe for the rest of our lives. It's not a threat; it's just an experience and by using the proper management techniques we can probably put up with more pain than we think we can - now that would be an achievement in itself! Try not to dismiss the idea because pain is so entrenched in your life and try to be open to change. All that said, I too live with daily pain and I too take the drugs to dampen it but I wish I didn't, so if there are effective methods to learn to live with it and reduce its importance, bring them on! For that, we need doctors who are willing to say:' less pills, better management and here's how.'
 

Deciding when to say when: pain cure? or pain managed?
Bronwyn Thompson, PhD, MSc (Psych) 1st Class Hons, DipOT, Registered Occupational Therapist 

I think the subject of this post is the singularly most important yet neglected topic in chronic pain research today. When is it time to say “All this looking at pain cure, or reducing your pain isn’t working, it’s time to accept that pain is going to part of your life.” It’s difficult for so many reasons whether you’re the person experiencing the pain, or the clinician trying to help. It’s also incredibly important for everyone including our community.

Cures for pain that persists are not easily found. One possibility is that the underlying disease or dysfunction has not yet been treated – pain in this case is the experience we have when there’s an unresolved threat to body tissues. Find the source of the problem, treat it, and voila! No pain.

Another possibility is that a new or groovy treatment has been developed – something extraordinary, or something that’s being applied to a different problem or something that’s emerging from the experimental phase to clinical practice. This means clinicians need to have heard about it, maybe will have had to think hard about their clinical reasoning, have developed skills to apply it, and be ready to talk about it with the person they’re treating.

In the case of much chronic pain, pharmacological approaches simply do not work. Machado and colleagues (2009), in a large meta-analysis of placebo-controlled randomised trials, found 76 eligible trials reporting on 34 treatments. Fifty percent of the treatments had statistically significant effects, but for most the effects were small or moderate … the analgesic effects of many treatments for non-specific low back pain are small”, while Machado, Maher and colleagues found that paracetamol was “ineffective” for reducing pain intensity or improving quality of life for people with low back pain, and although there was a statistically significant result for paracetamol on osteoarthritis pain (hip or knee), this was not clinically important (Machado, Maher, Ferreira, Pinheiro, Lin, et al_2015). Clifford Woolf said “most existing analgesics for persistent pain are relatively ineffective… the number of patients who are needed to be treated to achieve 50% reduction in neuropathic pain in one patient is more than four – a high cost for the three unsuccessfully treated patients and their physicians” (Woolf, 2010).

Woolf’s sentence ends with an important statement: A high cost for the three unsuccessfully treated patients and their physicians. I have emphasised the final three words, because this might be the most difficult to process. It’s hard for clinicians to say “I can’t reduce your pain”, and “there isn’t a cure”. It’s incredibly hard. And it’s perhaps because it’s so hard that I’ve found very little published research looking at the way clinicians go about telling people their pain is likely to be ongoing. It’s like a taboo – let’s not talk about it, let’s pretend it doesn’t happen, after all it doesn’t happen often. Really?

Amongst allied health (I can’t bear to use the word “non-medical”), and in particular, physiotherapists, there continues to be a push to address pain intensity and (ultimately) to cure pain. Innovative treatments such as mirror therapy, graded motor imagery, therapeutic pain neuroscience (we used to call it psycho-education in the 1980’s when I first started working in this area), reducing the threat value of the experience have all come into their own over the past 15 years or so. Even long-standing pain problems apparently respond to these approaches – people cured! Who wouldn’t be keen to try them?

Most of these latter treatments are based on the idea that our neurology is plastic; that is, it can change as we change input and thoughts/beliefs about what’s going on. Unfortunately, the systematic reviews of trials, and at least one “real world” trial of graded motor imagery haven’t shown effects as great as promised from the early research (eg Johnson, Hall, Barnett, Draper, Derbyshire et al, 2012). There are sure to be people who can point to amazing outcomes in the people they treat. I’m certain that it’s not just the “treatment” but an awful lot to do with the person delivering the treatment – and the treatment context – that might make a difference to outcomes.

But where this all leads me to is who makes the decision to stop chasing pain reduction and pain cure? When does it happen? What’s the process? And what if we treatment providers are actually prolonging disability out of the goodness of our hearts to find a cure?

Let me unpack this a little.

In my research, several important factors led to people deciding to begin flexibly persisting (and getting on with life as it is, not as it was, or might be).
The first was knowing the diagnosis and that it would not be completely cured but could be managed.
The second, that hurting didn’t mean harm (pain is just pain, not a sign of ongoing damage).
The third, that there was something important the person wanted or needed to do to be themselves.

There were other things as well, like having a clinician who would stand by the person even if the person didn’t “do as the Doctor ordered”, and developing their own personalised model or explanation for their pain as it fluctuated from day-to-day. BUT the single most important factor was knowing that the problem needed to be managed because there was no cure. Knowing this meant that energy used chasing a cure was redirected towards learning to live well and be the person they were, rather than a patient or being dominated by pain.

Unfortunately, I think that many clinicians confuse the idea of managing pain with that of resignation to a lesser life. Even the wonderful Lorimer Moseley and crew wrote recently that “CBT literature seemed to focus on this idea of ‘pain is now unavoidable so it is now time to learn how to cope with it.’ He goes on to argue that because a CBT approach focuses on thoughts and beliefs (much like Explain Pain does), it’s not incompatible with the idea that the plastic brain can learn to reduce the threat value even further to ultimately “helping them live well with less pain, or perhaps without any pain at all.”

Here’s my concern: Right now there are many people living with chronic pain who have lost their sense of hope. They’ve pursued pain cure after pain cure, and in doing so, they’ve lost normal routines and habits, lost their usual occupations (activities), stopped being around people, stopped working, and have suffered in the true sense of the word – they’ve lost their sense of self. While I applaud the efforts of researchers like Moseley and colleagues, and I think we must continue to seek treatments to reverse the neurobiological underpinnings of pain, at the same time I think we need to look at the psychological and social aspects of our attitudes and expectations towards experiencing pain. And we must think of the negative effects of our emotional response to seeing another person who is experiencing pain.

Is it so terrible to experience pain every day? Speaking as one who does – despite my knowledge of neuroplasticity – my pain doesn’t represent a threat. It’s just an experience. It’s there. I notice it, I can feel it. And the participants in my research similarly acknowledged pain as present – but it didn’t have the emotional primacy that pain can represent before it is explained. In fact, some of the participants said they’d learned important things because they’d had pain. A lot like having a mood disorder (that must be managed), or diabetes (that must be managed), or heart disease (that must be managed), or respiratory disease (that must be managed), perhaps it’s OK to have pain – that must be managed. Because until our research has advanced a LOT further than it has, there are an awful lot of people living with chronic pain, and who will continue to live with chronic pain. And even more sadly, there are an awful lot of people who don’t even get the opportunity to know that it’s possible to live well despite experiencing chronic pain because we (as part of society) still don’t accept that pain can be present without it being a threat.

Sometimes I wonder at our (clinicians and researchers) blind spot. We just don’t seem to be ready to accept persisting pain as something that can be lived with. Is it time to look at our own discomfort with allowing pain to be part of life?

Sources

Bowering, K. J., O’Connell, N. E., Tabor, A., Catley, M. J., Leake, H. B., Moseley, G. L., & Stanton, T. R. (2013). The effects of graded motor imagery and its components on chronic pain: a systematic review and meta-analysis. Journal of Pain, 14(1), 3-13.

Cossins, L., Okell, R. W., Cameron, H., Simpson, B., Poole, H. M., & Goebel, A. (2013). Treatment of complex regional pain syndrome in adults: a systematic review of randomized controlled trials published from June 2000 to February 2012. European Journal of Pain, 17(2), 158-173.

Johnson, S., Hall, J., Barnett, S., Draper, M., Derbyshire, G., Haynes, L., . . . Goebel, A. (2012). Using graded motor imagery for complex regional pain syndrome in clinical practice: failure to improve pain. European Journal of Pain, 16(4), 550-561.

Machado, LAC, Kamper, SJ, Herbert, RD, Maher, CG, & McAuley, JH. (2009). Analgesic effects of treatments for non-specific low back pain: a meta-analysis of placebo-controlled randomized trials. Rheumatology, 48(5), 520-527.

Machado, Gustavo C, Maher, Chris G, Ferreira, Paulo H, Pinheiro, Marina B, Lin, Chung-Wei Christine, Day, Richard O, . . . Ferreira, Manuela L. (2015). Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials (Vol. 350).

Woolf, Clifford J. (2010). Overcoming obstacles to developing new analgesics. Nature Medical, 16(11), 1241-1247. doi: doi:10.1038/nm.2230

https://healthskills.wordpress.com/2015/07/27/deciding-when-to-say-when-pain-cure-or-pain-managed/

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!"

Post Herpetic Neuralgia Related To Neuropathic Disorders

Today's short post from painhq.org (see link below) looks at postherpetic neuralgia which is a neurological extension of shingles. It's strange, almost everyone has heard of shingles and rightfully fears it for the pain it can bring but few associate it with neuropathy, yet in fact, it's one of the many forms of nerve damage that can fall under the general term of neuropathy. Shingles is a neuropathy caused by the reawakening of the varicella zoster virus, the same virus that causes chickenpox. In that respect it can be related to other forms of neuropathy brought about by viruses, such as HIV. This article sticks to the point and gives you a decent springboard for further research if you're suffering from either shingles or the misery of postherpetic neuralgia.
 

Postherpetic Neuralgia 
Info from Mayo Clinic and Wikipedia: Author unknown: 2014

What is Postherpetic Neuralgia? Postherpetic neuralgia is ​a complication of shingles. A case of shingles will typically only last a few weeks. If pain remains after the blisters and skin irritations subside, postherpetic neuralgia may be diagnosed. Early treatment of shingles can reduce the risk of developing postherpetic neuralgia.

Nerve fibres in the skin can be damaged during an outbreak of shingles, and the virus may remain resident in the nerve cell. When this happens, the nerves in the skin cannot communicate properly with the brain, resulting in postherpetic neuralgia.

What are the symptoms? Symptoms for postherpetic neuralgia present in the distribution of the nerve affected by the shingles. Individuals may experience a burning, sharp pain and a sensitivity to light touch (which may even include the touch of clothing against the skin). Less commonly, patients may experience a numb or itchy feeling in the affected areas, and in some cases, muscle weakness or paralysis.

Is there any treatment? Often a combination of different treatments are used to manage postherpetic neuralgia and any associated pain. Treatments include the use of topical medicines applied to the skin itself, such as lidocaine and capsaicin skin patches; as well as medicines taken by mouth such as anticonvulsants, antidepressants and opioid painkillers.

What treatment have you found most effective for Postherpetic Neuralgia?

Opioids (0)
Physical Therapy and Rehabilitation (0)
Gabapentin (1)
Pregabalin (1)
Topical Lidocaine (1)
Duloxetine (0)

What is the prognosis? Most individuals suffering from postherpetic neuralgia will experience a slow improvement of pain symptoms with treatment.

Related evidence 
Markley HG, Dunteman ED, Sweeney M. Real-World Experience with Once-Daily Gabapentin for the Treatment of Postherpetic Neuralgia (PHN). Clin J Pain. 2014 Jul 28. [Epub ahead of print]

Schlereth T, Heiland A, Breimhorst M, Féchir M, Kern U, Magerl W, Birklein F. Association between pain, central sensitization and anxiety in postherpetic neuralgia. Eur J Pain. 2014 Jul 28. doi: 10.1002/ejp.537. [Epub ahead of print]

References  
Mayo Clinic [Internet]. Postherpetic neuralgia [updated 2014; cited 2014 Aug 5]. Available from: http://www.mayoclinic.org/diseases-conditions/postherpetic-neuralgia/basics/definition/con-20023743

Wikipedia [Internet]. Postherpetic neuralgia [updated 2014 Aug 16; cited 2014 Aug 5]. Available from: http://en.wikipedia.org/wiki/Postherpetic_neuralgia
 
https://www.painhq.org/learning/knowledge-base/category/conditions/peripheral-neuropathic-pain/post-herpetic-neuralgia

Autonomic Neuropathy What To Look Out For

Today's very short post from mayoclinic.org (see link below) responds to a frequent question here on the blog: "How do I know if I have autonomic neuropathy?" First let's reiterate what autonomic neuropathy is. If you find that your neuropathy symptoms begin to affect the bodily functions which we call 'involuntary. (you have no control over them - they function automatically) such as breathing, digestion, sexual response, sweating, eyesight etc, then it's possible you have autonomic neuropathy. As a general rule, you will already be experiencing neuropathic symptoms in your feet, legs or hands but may notice that other aspects of your life don't function as they should any more. That's the time to ask your doctor if your nerve damage is affecting other areas of your body. This post lists the most common symptoms of autonomic neuropathy and should serve as a starting point for further investigation. The problem is of course, that there could be any number of other reasons why this is happening. That's why it's important to seek advice as soon as you realise something's wrong. Autonomic neuropathy can seriously affect your quality of life, so delaying seeing your doctor could make things worse.

Autonomic Neuropathy Symptoms
By Mayo Clinic Staff

Signs and symptoms of autonomic neuropathy vary based on the nerves affected. They may include:

Dizziness and fainting when standing caused by a sudden drop in blood pressure.

Urinary problems, such as difficulty starting urination, incontinence, difficulty sensing a full bladder and inability to completely empty the bladder, which can lead to urinary tract infections.

Sexual difficulties, including problems achieving or maintaining an erection (erectile dysfunction) or ejaculation problems in men and vaginal dryness, low libido and difficulty reaching orgasm in women.

Difficulty digesting food, such as feeling full after a few bites of food, loss of appetite, diarrhea, constipation, abdominal bloating, nausea, vomiting, difficulty swallowing and heartburn, all due to changes in digestive function.

Sweating abnormalities, such as sweating too much or too little, which affects the ability to regulate body temperature.

Sluggish pupil reaction, making it difficult to adjust from light to dark and seeing well when driving at night.

Exercise intolerance, which may occur if your heart rate stays the same instead of adjusting in response to your activity level. 

When to see a doctor

Seek medical care promptly if you begin experiencing any of the signs and symptoms of autonomic neuropathy, particularly if you have diabetes and it's poorly controlled.

If you have type 2 diabetes, the American Diabetes Association (the Association) recommends annual autonomic neuropathy screening for people with type 2 diabetes as soon as you've received your diabetes diagnosis. For people with type 1 diabetes, the Association advises annual screening beginning five years after diagnosis.

http://www.mayoclinic.org/diseases-conditions/autonomic-neuropathy/basics/symptoms/con-20029053

Celebs With Neuropathy Hard To Find

Finding well-known people who also have neuropathy is like searching for the proverbial needle in the haystack. Today's extract from a neurocentre.com (see link below) page shows two people who may be better known to Brits than elsewhere in the world. Norman Wisdom was a famous comic actor (incredibly popular in Albania of all places) and  Warren Mitchell played the notorious Alf Garnett in the 70's (way too politically incorrect for 2012 but funny at the time). They have given their support over the years to the Neuropathy Trust. Unfortunately Sir Norman Wisdom has now died and we could really do with a few more celebrity role-models, so if you know of anyone, please let us know. That organisation is a very well known independent neuropathy charity that operates across the world.

What is the Neuropathy Trust?

The Neuropathy Trust is a worldwide Charity (1071228) that was founded in 1998 by Andrew Keen to provide a lifeline to people affected by Peripheral Neuropathy (PN) and Neuropathic Pain (NeP). It is the primary function of the Trust to ensure, irrespective of the cause of the peripheral neuropathy or neuropathic pain (whether known or otherwise) that patients, family, carers and health care providers receive the highest possible level of information and support. The Neuropathy Trust is independent of any government, political ideology, economic interest or religionWell Known Supporters

Warren Mitchell

“About twenty years ago a virus attacked the nerves in my spine, leaving me temporarily paralysed from the waist down. I was working on a film in Australia at that time and, although I discharged myself from hospital in order to carry on working, those were some of the toughest days in my life. Although I couldn’t stand or move around during a scene, for example, the film-crew propped me up and gave me every help so that we could carry on filming. Afterwards I went back to hospital in Sydney and had lots of physiotherapy for two weeks. I was very fortunate because I was soon walking again and within six weeks I was tap dancing on another film set. I have, however, been left with residual neurological effects which do trouble me greatly. My feet, for example, really do feel as if they are sometimes going to explode; at times they are burning and other times freezing cold. I also have strange tingly sensations in my legs and a degree of spasticity because my nervous system has been damaged permanently. After my article appeared in the paper the Neuropathy Trust sent me some information and I know there are lots of you out there who are in a far worse condition than myself. I am lucky that my dear wife Connie is so supportive and allows me one self-pitying moan per week. It is reassuring to know that doctors and scientists the world over are now working hard, trying to find ways to overcome the damage to nervous systems and relieve the pain which can affect the quality of life so much. I wish them all well in their research.”

Previous Patrons
Sir Norman Joseph Wisdom, OBE (4 February 1915 – 4 October 2010) RIP Old Chum!

“When I was approached to become Patron of the Neuropathy Trust, I was delighted to offer my support and endorsement to such a worthy cause. What has impressed me the most about this organisation is the positive and encouraging manner in which it is tackling the huge task that it has undertaken.
The Trust, which has been founded upon the motto ‘Carpe Diem’ (Seize the Day), is proving to be a tremendous source of comfort and inspiration to many thousands of people affected by Peripheral Neuropathy and associated neuropathic conditions. It is bringing together people from all over the world, offering hope and a sense of purpose and worth to families, friends and carers. It is helping to bridge communications between patients and the medical profession, for the benefit of all concerned.
This important work must be encouraged and sustained and I would urge you to join in with me in supporting this charity.”

http://neurocentre.com/community/?page_id=2

Peptide Activates Receptor To Reduce Neuropathic Pain

Today's post from sciencedaily.com (see link below) looks at trials of ARA 290, which is a peptide. Peptides are naturally occurring biological molecules but that won't mean much to most people either. Put very simply, when neuropathic damage occurs, the nervous system's normal repair receptors are turned off. When ARA 290 is introduced, the repair receptor is reactivated, which in turn represses inflammation and restores the body's natural ability to repair damage. I know; it's incredibly difficult for the layman to understand but if you read the article, you should get the point. Basically, molecular science is being used to find a way for pain signals to be dampened and we should see that as good news. A feature of the last couple of years, is the emergence of news in the stem-cell and molecular science areas, that shows that neuropathic pain is being taken very seriously and there are serious efforts to find ways to tackle it. We don't have to understand exactly how it works but knowing that it shows progress towards a positive result for us all, is very reassuring. All we have to do now is wait and hope that they get to practical treatments as soon as possible.

Novel agent decreases neuropathic pain in patients with type 2 diabetes  Source: North Shore-Long Island Jewish (LIJ) Health System Date: December 15, 2014

Summary:

A promising profile of disease modification and pain reduction leads to proof-of-concept trials, scientists report. "The results from this study indicate a major breakthrough in the treatment of diabetes," said one expert.

Molecular Medicine, a peer-reviewed biomedical journal published by the Feinstein Institute Press, published the results of a new study reporting clinically significant pain reduction in type 2 diabetic patients. In an exploratory study conducted by Araim Pharmaceuticals, a biotech company developing novel treatments for chronic diseases, investigators also observed improvements in metabolic control in patients administered ARA 290. ARA 290 is a peptide engineered to activate the innate repair receptor, a receptor discovered by Araim scientists, which is only expressed following tissue damage or stress.

In the initial study, patients were administered ARA 290, a novel, first-in-class drug, daily for 28 days, with the purpose of evaluating its efficacy in treating neuropathic pain, a common condition among diabetics. When ARA 290 is administered, the repair receptor is activated and subsequently turns off inflammation and turns on the body's natural repair system. The short half-life of ARA 290, coupled with the restricted expression of the innate repair receptor, functions as a dual safety system to avoid potential side effects.

"The results from this study indicate a major breakthrough in the treatment of diabetes," said Kevin J. Tracey, MD, president of the Feinstein Institute for Medical Research and Editor of Molecular Medicine. "Over the years, Molecular Medicine has prided itself on publishing groundbreaking papers with implications on the broader medical community, and we're proud to have a potential disease-modifying solution to diabetes featured in the current issue."

The clinically significant results and excellent safety profile support Araim's development strategy of two future studies in 2015. First, metabolic improvement will be studied in type 2 diabetics with moderate kidney damage. Second, neuropathic pain reduction will be assessed in a multi-center proof of concept trial in type 1 diabetics. Both phase 2 clinical trials will be conducted in the United Kingdom, and patients will be dosed daily for six months to allow time for adequate tissue repair.

"We're excited to be on the cusp of the first diabetic disease modifier that demonstrates the potential to repair the complications of diabetes systemically," said Anthony Cerami, PhD, CEO of Araim Pharmaceuticals." Dr. Cerami developed the HbA1c diagnostic test, the current gold standard for diagnosing diabetes.

Story Source:

The above story is based on materials provided by North Shore-Long Island Jewish (LIJ) Health System. Note: Materials may be edited for content and length.

http://www.sciencedaily.com/releases/2014/12/141215101647.htm