NEW ANTIBIOTIC ATTACK S DRUG RESISTANT MICROBES

The multitude of microbes scientists have found populating the human body have good, bad and mostly mysterious implications for our health. But when something goes wrong, we defend ourselves with the undiscriminating brute force of traditional antibiotics, which wipe out everything at once, regardless of the consequences.

Researchers at Rockefeller University and their collaborators are working on a smarter antibiotic. And in research to be published October 5 in Nature Biotechnology, the team describes a 'programmable' antibiotic technique that selectively targets the bad bugs, particularly those harboring antibiotic resistance genes, while leaving other, more innocent microbes alone.

"In experiments, we succeeded in instructing a bacterial enzyme, known as Cas9, to target a particular DNA sequence and cut it up," says lead researcher Luciano Marraffini, head of the Laboratory of Bacteriology. "This selective approach leaves the healthy microbial community intact, and our experiments suggest that by doing so you can keep resistance in check and so prevent certain types of secondary infections, eliminating two serious hazards associated with treatment by classical antibiotics."

The new approach could, for instance, reduce the risk of C. diff, a severe infection of the colon, caused by the Clostridium difficile bacterium, that is associated with prolonged courses of harsh antibiotics and is a growing public health concern.

The Cas9 enzyme is part of a defense system that bacteria use to protect themselves against viruses. The team coopted this bacterial version of an immune system, known as a CRISPR (clustered regularly interspaced short palindromic repeats) system and turned it against some of the microbes. CRISPR systems contain unique genetic sequences called spacers that correspond to sequences in viruses. CRISPR-associated enzymes, including Cas9, use these spacer sequences as guides to identify and destroy viral invaders.

The researchers were able to direct Cas9 at targets of their choosing by engineering spacer sequences to match bacterial genes then inserting these sequences into a cell along with the Cas9 gene. The cell's own machinery then turns on the system. Depending on the location of the target in a bacterial cell, Cas9 may kill the cell or it may eradicate the target gene. In some cases, a treatment may prevent a cell from acquiring resistance, they found.

"We previously showed that if Cas9 is programmed with a target from a bacterial genome, it will kill the bacteria. Building on that work, we selected guide sequences that enabled us to selectively kill a particular strain of microbe from within a mixed population," says first author David Bikard, a former Rockefeller postdoc who is now at the Pasteur Institute in Paris.

In initial experiments, Bikard and colleagues targeted a strain of the common skin and respiratory bacteria Staphylococcus aureus that is resistant to the antibiotic kanamycin. Treatment by Cas9 programmed to target a part of the resistance gene killed most of the resistant Staph, but left behind the kanamycin-susceptible Staph.

Targeted bacterial genocide is only one option. Bacteria share genes, including those conferring drug resistance, in the form of rings of DNA known as plasmids. In a second series of experiments, researchers turned Cas9 on tetracycline resistance-harboring plasmids in a strain of the potentially deadly multidrug resistant bacteriaStaphylococcus aureus (MRSA). Not only did the resistant cells become sensitive to tetracycline after Cas9 destroyed the plasmids, but the arrival of Cas9 in other Staphcells acted as an immunization, preventing them from taking on resistance-carrying plasmids.

And, in a final set of experiments, conducted in collaboration with Vincent Fischetti's Laboratory of Bacterial Pathogenesis and Immunology, adjunct faculty member Chad Euler confirmed their test tube results on living skin, by using Cas9 to selectively kill kanamycin-resistant Staph infecting the shaved backs of mice.

In spite of the promising results, the delivery system needs improvement. The researchers used bacteria-infecting viruses to inject the programmed Cas9 enzymes into the bacterial cells, but these viruses only attack specific types of cells. Scientists need to devise a less discriminating method of delivery, before the technology can be used to develop a new class of antibiotics, Marraffini says.

In addition to its potential as a much-needed new weapon against drug-resistant microbes, the new system could also be used to advance research on the complex populations of microbes in the body, about which very little is known. "There are enormous microbial communities in the human body," Marraffini says. "Programmable Cas9 enzymes may make it possible to analyze these populations by eliminating their members, one by one, and studying the effects."

New Book About Neuropathy Jan 2014

Today's post from novapublishers.com (see link below) is another advertisement for a new book about Neuropathy. We normally don't advertise for publishers, in the same way that we don't advertise for clinics or private companies but if the book seems to be a taking a slightly different approach, it may offer more information to its readers than the standard texts. There are many books about neuropathy available and this one does state that they aim to 'challenge' their readers, which may mean that it's difficult to read, however, ordering it via a library, or glancing through in a bookshop may help with your decision as to whether it's going to help you or not. It does discuss neuropathies associated with HIV infection, where many others avoid the subject completely.

Contemporary Issues in Peripheral Neuropathy

Editors: Daniel L. Menkes (UCHC Neurology Department, Farmington, Connecticut, USA)

Book Description: There are many books on polyneuropathy available that are comprehensive in nature. Many of these are encyclopedic in their scope. However, there are very few books that review the basics of clinical neurophysiological testing, genetics and the commonly encountered neuropathies. There are even fewer that are willing to address less commonly encountered neuropathies such as amyloidosis and neuropathies associated with HIV infection. Many such textbooks also avoid interdisciplinary topics such as the management of pelvic floor dysfunction and the surgical treatment of compression and traumatic neuropathies. This book addresses this void by dividing this book into three distinct sections. The first three chapter section addresses basic clinical neurophysiological techniques, genetic testing and the inherited neuropathies. The larger middle section addresses acquired demyelinating neuropathies, monoclonal gammopathies, HIV neuropathy and familial amyloidosis. The final section concludes with a summary of neuropathies affecting pelvic function and a plastic surgeon’s approach to the treatment of compression and traumatic neuropathies. The authors who wrote these chapters have extensive expertise in these topics such that the literature review was comprehensive. The final chapter on the surgical treatment of compression neuropathies may be viewed as controversial by some and even heretical by others but it provides a unique perspective on the management of patients who are symptomatic and yet have relatively unremarkable clinical and electrodiagnostic investigations. The reader will find up to date information on a variety of topics; common and uncommon. This book attempts to educate as well as challenge the reader. (Imprint: Nova Biomedical)

Table of Contents: Preface Chapter 1. The Role of Clinical Neurophysiology in the Diagnosis of Peripheral Neuropathies (Elisabeth Chroni, Department of Neurology, University of Patras, Greece) Chapter 2. Role of Genetic Testing in Peripheral Neuropathy (Charles H. Whitaker, University of Connecticut Health Center Farmington, Connecticut, USA and others) Chapter 3. Hereditary Peripheral Neuropathies (Meriem Tazir, Mounia Bellatache and Sonia Nouioua, Service de Neurologie, CHU Mustapha Bacha, Algiers, Algeria, and others) Chapter 4. Guillain–Barré Syndrome (Akiyuki Hiraga, Masahiro Mori and Satoshi Kuwabara, Department of Neurology, Graduate School of Medicine, Chiba University, Japan) Chapter 5. Evolving Concepts in the Pathogenesis of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) (Paolo Ripellino, Thomas Fleetwood, Roberto Cantello and Cristoforo Comi, Department of Translational Medicine, Section of Neurology and Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD), Amedeo Avogadro University, Novara, Italy) Chapter 6. Chronic Inflammatory Demyelinating Polyneuropathy in Children: A Pediatric Neurologist's Perspective (Christian Ionita, Connecticut Children's Medical Center/University of Connecticut Health Center, Connecticut, USA) Chapter 7. Monoclonal Gammopathy of Undetermined Significance and Polyneuropathy (Kam Newman, Ihab El-Hemaidi, Jagar A. Jasem and Mojtaba Akhtari, Section of Transfusion Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA and others) Chapter 8. Peripheral Neuropathies in HIV Infection (Maurizio Osio, Caterina Nascimbene, Alessandra Vanotti and Cristoforo Comi, Neurology Department. University of Milan, "L. Sacco" Hospital, Milan, Italy and others) Chapter 9. Familial Amyloid Polyneuropathy (FAP): Clinical Features, Pathophysiology, and Treatment (Mª Teresa Tomás, Helena Santa-Clara, Élia Mateus and Estela Monteiro, Exercise and Health Laboratory, Interdisciplinary Center for the Study of Human Performance, Lisbon, Portugal and others) Chapter 10. Peripheral Neuropathy in Pelvic Floor Dysfunction (Consuelo Valles-Antuna and Jesus M. Fernandez-Gomez, Hospital Universitario Central de Asturias, Universidad de Oviedo, Spain) Chapter 11. The Surgical Treatment of Peripheral Neuropathies: A Plastic Surgeon’s Perspective (Sean Wolfort, Surgery Department, Florida State University, and University of Central Florida, Florida, USA) Index

		https://www.novapublishers.com/catalog/product_info.php?products_id=46986&osCsid=1e608f8a26aa73770b1f10f4ab284d91

REPROGRAMMED CELLS GROW IN TO NEW BLOOD VESSELS

By transforming human scar cells into blood vessel cells, scientists at Houston Methodist may have discovered a new way to repair damaged tissue. The method, described in an upcoming issue of Circulation, appeared to improve blood flow, oxygenation, and nutrition to areas in need

Cardiovascular scientists at Houston Methodist, with colleagues at Stanford University and Cincinnati Children's Hospital, learned that fibroblasts -- cells that causes scarring and are plentiful throughout the human body -- can be coaxed into becoming endothelium, an entirely different type of adult cell that forms the lining of blood vessels.

"To our knowledge, this is the first time that trans-differentiation to a therapeutic cell type has been accomplished with a small molecules and proteins," said Houston Methodist Research Institute Department of Cardiovascular Sciences Chair John Cooke, M.D., Ph.D., the study's principal investigator. "In this particular case, we've found a way to turn fibroblasts into 'shapeshifters' nearly on command."

Cooke said the regenerative medicine approach provides proof-of-concept for a small molecule therapy that could one day be used to improve the healing of cardiovascular damage or other injuries.

Other research groups have managed to generate endothelial cells cells using infectious virus particles specially engineered to deliver gene-manipulating DNA to cells. The DNA encodes proteins called transcription factors to alter gene expression patterns in such a way that cells behave more like endothelial cells.

"There are problems with using viruses to transfer genes into cells," Cooke said. "This gene therapy approach is more complicated, and using viral vectors means the possibility of causing damage to the patient's chromosomes. We believe a small-molecule approach to transforming the cells will be far more feasible and safer for clinical therapies."

The new method described by Cooke and his coauthors starts with exposing fibroblasts to poly I:C (polyinosinic:polycytidylic acid), a small segment of double-stranded RNA that binds to the host cell receptor TLR3 (toll-like receptor 3), tricking the cells into reacting as if attacked by a virus. Cooke and coauthors reported to Cell in 2012 that fibroblasts' response to a viral attack -- or, in this case, a fake viral attack -- appears to be a vital step in diverting fibroblasts toward a new cell fate. After treatment with poly I:C, the researchers observed a reorganization of nuclear chromatin, allowing previously blocked-off genes to be expressed. The fibroblasts were then treated with factors, such as VEGF, that are known to compel less differentiated cells into becoming endothelial cells.

Cooke and his colleagues reported to Circulation that about 2 percent of the fibroblasts were transformed from fibroblasts into endothelial cells, a rate comparable to what other research groups have accomplished using viruses and gene therapy. But Cooke said preliminary, as-yet-unpublished work by his group suggests they may be able to achieve transformation rates as high as 15 percent.

"That's about where we think the yield of transformed cells needs to be," Cooke said. "You don't want all of the fibroblasts to be transformed -- fibroblasts perform a number of important functions, including making proteins that hold tissue together. Our approach will transform some of the scar cells into blood vessel cells that will provide blood flow to heal the injury."

In a second part of the study, the scientists introduced the transformed human cells into immune-deficient mice that had poor blood flow to their hind limbs. The human blood vessel cells increased the number of vessels in the mouse limb, improving circulation.

"The cells spontaneously form new blood vessels -- they self assemble," Cooke said. "Our transformed cells appear to form capillaries in vivo that join with the existing vessels in the animal, as we saw mouse red blood cells inside the vessels composed of human cells."

Cooke, who is also the director of the Houston Methodist Center for Cardiovascular Regeneration, said that figuring out how to manipulate adult cells of one type into becoming a completely different type of cell will be an important part of the development of regenerative medicine as a scientific and clinical field. Humans are generally unable to regenerate heavily damaged tissue, whereas other animals, such as some newts and flat worms, can regenerate entire lost limbs -- even entire heads.

"It is likely that modifications of this small molecule approach may be used to generate other body cells of therapeutic interest," Cooke said. "What we are seeing is evidence of the fluidity of cell fate with the proper stimulation. If we can understand the underlying pathways and how to manipulate them, we may very well learn how reawaken primordial mechanisms for regeneration that are active in lower vertebrates such as newts."

Cooke said more animal model studies are needed before his group begins clinical trials.

"One of the next steps will be to see if we can rescue an animal from an injury," Cooke said. "We want to know if the therapy enhances healing by increasing blood flow to tissues that may have been damaged by a loss of blood because of ischemia."

Tests For New Drugs Are Too Often Rigged To Suit The Market

Today's post from pharmaciststeve.com (see link below) looks at the current drugs debate in North America from a different angle. It asks: just how trustworthy are the testing procedures on new drugs and just how safe are FDA approved (based on those testing procedures) drugs for patients? The answer is not reassuring. Now neuropathy patients know more than most how much research needs to be done on new drugs to treat nerve damage symptoms. They've also been guinea pigs in the search for new and relevant treatments and it's one of those diseases for whom, drugs work for some but not for others. We need to be able to trust the testing procedures and the drug research companies that carry them out and we also need to be able to trust the FDA's final conclusions. This article suggests that neither are rock-solid, so where does that leave us, who are desperate for new drug therapies? Well, it means that we have to be even more pro-active than before and do as much research as is humanly possible ourselves. Thank god for the internet - we can find most of what we need to know there and with advice from our doctors, we can draw our own conclusions. Unfortunately we can't separate politics from health at the moment.

Virtually every pharmaceutical company has been rigging tests for years to make the drugs we take look safer than they really are
Posted on December 27, 2015 by Pharmaciststeve
 
U.S. needs better regulation of drug development

Over the last weeks, we have learned that major companies that make products we trust, like Volkswagen’s diesel engines and Takata’s air bags, have devised ways to rig test results so they look cleaner and safer than they really are. Yet far more widespread manipulation of test results is being done by pharmaceutical companies to get drugs approved by the U.S. Food and Drug Administration that turn out not to be as safe as promised.

In the pharmaceutical industry, virtually every company has been rigging tests for years to make the drugs we take look safer than they really are. Some of the techniques for rigging clinical trials are described in a recent assessment published by BMJ (formerly known as the British Medical Journal). They include drawing random samples for clinical trials from a population that exclude older people, women, and people with multiple health problems who may be more likely to have adverse reactions. The resulting “safety” of the drugs misleads physicians and their patients.

Other techniques include using high doses in shorter trials in order to produce positive results before adverse reactions become evident. Only later do patients learn about them the hard way. FDA regulations also allow companies to run multiple trials (at great expense, used to justify high prices) and handpick the most positive ones while obscuring evidence of toxic reactions.

Worse, unlike regulators for cars, planes, electronic devices, and appliances, who work to detect and stop rigged testing, the FDA division that reviews new drugs has long known about the ways that companies bias trials. This puts patients at serious risk. Based on reviews of hospital clinical charts, independent experts estimate approximately 128,000 patients die each year from adverse responses to properly prescribed drugs. And 2.7 million are hospitalized due to drug reactions. Those estimates do not even include problems related to over-prescribing, errors, and self-prescribing.

Exactly which drugs approved by the FDA’s fast-track process have proved most dangerous to consumers? Given the central importance of drugs in modern medicine, you would think there would be a comprehensive tracking system at the FDA to provide this information by drug. But there isn’t.

In fact, perhaps the most famous such failure is Vioxx, which Merck finally withdrew – following years of obfuscation – after it was estimated to have killed about as many people as the U.S. military lost in the Vietnam War. Note, it was the manufacturer that pulled the drug, not the FDA.

But there are many examples. Worst Pills, Best Pills (www.worstpills.org) is a reputable, subscription-based project of the advocacy group Public Citizen that tracks safety information on nearly 2,000 drugs.

Why does the FDA permit biased company trials for safety and efficacy? Perhaps it has something to do with Congress’ underfunding of the FDA since the antiregulation period under President Ronald Reagan and then having companies fund the division that evaluates their drugs.

These practices subject patients to a double conflict of interest. First, companies test their own drugs for the public regulator, rather than having them tested independently. Then, companies pay the FDA a huge fee – $2.3 million in 2015 – to review each drug. Highly trained and skilled staff work hard to do thorough reviews. But the reviews are on the companies’ terms – their criteria, their trials, their data, their deadlines, their funded patient groups clamoring for approval, and their money.

Reviewers do turn back or turn down drug candidates. Yet 90 percent of the drugs the FDA approves are judged by independent reviewers to provide few or no clinical advantages for patients over existing drugs.

And because these new drugs are inadequately tested, the results are predictable. One in every five new drugs ends up causing enough serious harm to lead the FDA to add the most serious black box warning, or remove the drug from the market – after the harm has been done.

This risk increases to one in three when reviews are accelerated under a special (and legal) process, requiring even higher fees from drugmakers.

Do patients really want faster access to drugs that provide few or no new benefits and have substantial risks of serious harm? Do they want an FDA that largely serves the industry that funds it by approving many new minor variations to increase sales, without good testing for safety?

A few clinically superior drugs are developed each year. But accelerated reviews and low, loose FDA criteria encourage companies to develop more minor variations that will get through the approval process, rather than focus on major advances. To encourage more superior drugs, the FDA needs to require tests for real clinical advances compared to risks of harm.

We need a congressional investigation, with subpoena power, to investigate how the FDA allows manipulations of true randomized trials that understate risks of harm. We need to end a third conflict of interest that endangers patients: The same FDA group that approves drugs as “safe” is responsible for investigating evidence of harm. Only 10 percent of FDA staff are assigned to drug safety. We need an independent, well-funded watchdog for patient safety.

Most important, as a public agency charged with protecting people from unsafe drugs, the FDA needs to be funded entirely by taxpayers. Drugs are now the fourth leading cause of death in America, tied with stroke. The FDA needs to stop contributing to this problem and help reduce the number of patients exposed to risks of serious harm.

Donald Light is a widely published expert on drug policy and a professor of comparative health policy at Rowan University
 
 http://www.pharmaciststeve.com/?p=13009

New Drug Development May End Up Replacing Morphine

Today's post from sciencedaily.com (see link below) is an interesting new development in finding effective ways to block pain signals for people like neuropathy and cancer sufferers. New research has discovered new compounds which bind to specific molecules (opioid receptors) on nerve cells. Opioids do this already but we all know the dangers of opioids and addiction and the need for ever increasing dosages. These new compounds attach themselves to a different part of the nerve cell but work in the same way without the normal opioid side effects. That's the theory anyway and as with many of these promising developments, sometimes you wish they wouldn't tell us about them until they're almost in production. Getting patients' hopes up but then letting them wait for years can be demoralising in itself. However, it does sound very promising and this is an easy to read article even though it's looking at the science at a molecular level.

A Path to Lower-Risk Painkillers: Newly-Discovered Drug Target Paves Way for Alternatives to Morphine
This story is reprinted from materials provided by University of Michigan Health System June 10, 2013

 For patients managing cancer and other chronic health issues, painkillers such as morphine and Vicodin are often essential for pain relief. The body's natural tendency to develop tolerance to these medications, however, often requires patients to take higher doses -- increasing risks of harmful side effects and dependency.

Now, new research from the University of Michigan Health System and a major pharmaceutical company has identified a novel approach to moderate and severe pain therapy that paves the way for lower dosage painkillers. The findings appear in Proceedings of the National Academy of Sciences.

Drugs such as hydrocodone (the main ingredient of Vicodin) and oxycodone (Oxycontin) are often the best options for the treatment of moderate to severe pain for patients facing medical conditions ranging from a wisdom tooth extraction to cancer. The drugs bind to specific molecules (opioid receptors) on nerve cells in the brain and spinal cord to prevent the feeling of pain.

"We have for the first time discovered compounds that bind to an alternative site on the nerve opioid receptors and that have significant potential to enhance the drug's positive impact without increasing negative side effects," says co-author John Traynor, Ph.D., professor of pharmacology at the U-M Medical School.

"We are still in the very early stages of this research with a long way to go, but we believe identifying these compounds is a key step in revolutionizing the treatment of pain. This opens the door to developing pain relief medications that require lower doses to be effective, helping address the serious issues of tolerance and dependence that we see with conventional pain therapy."

Conventional drug treatments for pain work by targeting the so-called orthosteric site of the opioid receptor that provides pain relief. Targeting this site, however, is a double-edged sword because it is also responsible for all of the drug's unwanted side effects, such as constipation and respiratory depression. Tolerance also limits chronic use of the drugs because higher doses are required to maintain the same effect.

Using cell systems and mouse brain membranes, researchers have identified compounds that bind to a physically distinct and previously unknown "allosteric" site on the opioid receptor- a site that fine-tunes the activity of the receptor. Not only do these compounds act at a location that hasn't been studied as a drug target before but they bind to the receptor in a new way to enhance the actions of morphine -- which means lower doses can have the same impact.

"The newly-discovered compounds bind to the same receptor as morphine but appear to act at a separate novel site on the receptor and therefore can produce different effects. What's particularly exciting is that these compounds could potentially work with the body's own natural painkillers to manage pain," Traynor says.

"We know that conventional strong pain medications ultimately increase the risk of withdrawal symptoms and addiction, which is an especially serious issue with the current prescription drug abuse epidemic in our country. The implications of this work, if it translates to animal studies and then to humans, are highly significant to this area of study."

http://www.sciencedaily.com/releases/2013/06/130610192553.htm

Growing New Nerves

Today's interesting post comes from sciencedaily.com (see link below) and talks about the work being done in a US research lab to encourage brain cells to create healthy nerves by introducing polymer nanofibres. The 'new' nerves can even grow a myelin layer (the protective sheath around healthy nerves). As with all these things, when they're first reported by researchers, the work is only in very early stages but the potential for 'growing' new nerves to replace damaged ones, or 'repair' damaged nerves themselves, gives hope for treatments of neuropathy in the future. The article is a little 'technical' but still understandable and it may be worth keeping an eye out for any progress in this area.

Researchers Coax Cells to Grow and Myelinate Along Thin Fibers; Potential Use in Testing Treatments for Neurological Diseases
ScienceDaily (Nov. 7, 2012)

Every week in his clinic at the University of Michigan, neurologist Joseph Corey, M.D., Ph.D., treats patients whose nerves are dying or shrinking due to disease or injury.

He sees the pain, the loss of ability and the other effects that nerve-destroying conditions cause -- and wishes he could give patients more effective treatments than what's available, or regenerate their nerves. Then he heads to his research lab at the VA Ann Arbor Healthcare System, where his team is working toward that exact goal.

In new research published in several recent papers, Corey and his colleagues from the U-M Medical School, VAAAHS and the University of California, San Francisco report success in developing polymer nanofiber technologies for understanding how nerves form, why they don't reconnect after injury, and what can be done to prevent or slow damage.

Using polymer nanofibers thinner than human hairs as scaffolds, researchers coaxed a particular type of brain cell to wrap around fibers that mimic the shape and size of nerves found in the body.

They've even managed to encourage the process of myelination -- the formation of a protective coating that guards larger nerve fibers from damage. They began to see multiple concentric layers of the protective substance called myelin start to form, just as they do in the body. Together with the laboratory team of their collaborator Jonah Chan at UCSF, the authors reported the findings in Nature Methods.

The research involves oligodendrocytes, which are the supporting actors to neurons -- the "stars" of the central nervous system. Without oligodendrocytes, central nervous system neurons can't effectively transmit the electrical signals that control everything from muscle movement to brain function.

Oligodendrocytes are the type of cells typically affected by multiple sclerosis, and loss of myelin is a hallmark of that debilitating disease.

The researchers have also determined the optimum diameter for the nanofibers to support this process -- giving important new clues to answer the question of why some nerves are myelinated and some aren't.

While they haven't yet created fully functioning "nerves in a dish," the researchers believe their work offers a new way to study nerves and test treatment possibilities. Corey, an assistant professor of neurology and biomedical engineering at the U-M Medical School and researcher in the VA Geriatrics Research, Education and Clinical Center, explains that the thin fibers are crucial for the success of the work.

"If it's about the same length and diameter as a neuron, the nerve cells follow it and their shape and location conform to it," he says. "Essentially, these fibers are the same size as a neuron."

The researchers used polystyrene, a common plastic, to make fibers through a technique called electrospinnning. In a recent paper in Materials Science and Engineering C, they discovered new techniques to optimize how fibers made from poly-L-lactide, a biodegradable polymer, can be better aligned to resemble neurons and to guide regenerating nerve cells.

They're also working to determine the factors that make oligodendrocytes attach to the long narrow axons of neurons, and perhaps to start forming myelin sheaths too.

By attaching particular molecules to the nanofibers, Corey and his colleagues hope to learn more about what makes this process work -- and what makes it go awry, as in diseases caused by poor nerve development.

"What we need to do for multiple sclerosis is to encourage nerves to remyelinate," he says. "For nerve damage caused by trauma, on the other hand, we need to encourage regeneration."

In addition to Corey, the research has been led by Chan, the Rachleff Professor of Neurology at UCSF, VAAAHS lab team member and U-M graduate Samuel J. Tuck, U-M biomedical engineering graduate student Michelle Leach, UCSF's Stephanie Redmond, Seonook Lee, Synthia Mellon and S.Y. Christin Chong, and Zhang-Qi Feng of U-M Biomedical Engineering.

Peripheral nerves, which have neurons at the center surrounded by cells called Schwann cells, can also be studied using the nanofiber technique. The system could also be used to study how different types of cells interact during and after nerve formation.

Toward creating new nerves, Corey's lab has collaborated with R. Keith Duncan, PhD, Associate Professor of Otolaryngology. Published in Biomacromolecules, they found that stem cells are more likely to develop into neurons when they are grown on aligned nanofibers produced in Corey's lab. They eventually hope to use this approach to build new nerves from stem cells and direct their connections to undamaged parts of the brain and to muscle.

Eventually, Corey envisions, perhaps nerves could be grown along nanofibers in a lab setting and then transferred to patients' bodies, where the fiber would safely degrade.

The research was supported by a VA Merit funding grant, the US National Multiple Sclerosis Society, the Harry Weaver Neuroscience Scholar Award, the Paralyzed Veterans of America and the National Institute of Neurological Disorders and Stroke (NS062796-02).

http://www.sciencedaily.com/releases/2012/11/121107145920.htm

NEW NANOGEL FOR DRUG DELIVERY

Scientists are interested in using gels to deliver drugs because they can be molded into specific shapes and designed to release their payload over a specified time period. However, current versions aren't always practical because must be implanted surgically.

To help overcome that obstacle, MIT chemical engineers have designed a new type of self-healing hydrogel that could be injected through a syringe. Such gels, which can carry one or two drugs at a time, could be useful for treating cancer, macular degeneration, or heart disease, among other diseases, the researchers say.

The new gel consists of a mesh network made of two components: nanoparticles made of polymers entwined within strands of another polymer, such as cellulose.

"Now you have a gel that can change shape when you apply stress to it, and then, importantly, it can re-heal when you relax those forces. That allows you to squeeze it through a syringe or a needle and get it into the body without surgery," says Mark Tibbitt, a postdoc at MIT's Koch Institute for Integrative Cancer Research and one of the lead authors of a paper describing the gel in Nature Communications on Feb. 19.

Koch Institute postdoc Eric Appel is also a lead author of the paper, and the paper's senior author is Robert Langer, the David H. Koch Institute Professor at MIT. Other authors are postdoc Matthew Webber, undergraduate Bradley Mattix, and postdoc Omid Veiseh.

Heal thyself

Scientists have previously constructed hydrogels for biomedical uses by forming irreversible chemical linkages between polymers. These gels, used to make soft contact lenses, among other applications, are tough and sturdy, but once they are formed their shape cannot easily be altered.

The MIT team set out to create a gel that could survive strong mechanical forces, known as shear forces, and then reform itself. Other researchers have created such gels by engineering proteins that self-assemble into hydrogels, but this approach requires complex biochemical processes. The MIT team wanted to design something simpler.

"We're working with really simple materials," Tibbitt says. "They don't require any advanced chemical functionalization."

The MIT approach relies on a combination of two readily available components. One is a type of nanoparticle formed of PEG-PLA copolymers, first developed in Langer's lab decades ago and now commonly used to package and deliver drugs. To form a hydrogel, the researchers mixed these particles with a polymer -- in this case, cellulose.

Each polymer chain forms weak bonds with many nanoparticles, producing a loosely woven lattice of polymers and nanoparticles. Because each attachment point is fairly weak, the bonds break apart under mechanical stress, such as when injected through a syringe. When the shear forces are over, the polymers and nanoparticles form new attachments with different partners, healing the gel.

Using two components to form the gel also gives the researchers the opportunity to deliver two different drugs at the same time. PEG-PLA nanoparticles have an inner core that is ideally suited to carry hydrophobic small-molecule drugs, which include many chemotherapy drugs. Meanwhile, the polymers, which exist in a watery solution, can carry hydrophilic molecules such as proteins, including antibodies and growth factors.

Long-term drug delivery

In this study, the researchers showed that the gels survived injection under the skin of mice and successfully released two drugs, one hydrophobic and one hydrophilic, over several days.

This type of gel offers an important advantage over injecting a liquid solution of drug-delivery nanoparticles: While a solution will immediately disperse throughout the body, the gel stays in place after injection, allowing the drug to be targeted to a specific tissue. Furthermore, the properties of each gel component can be tuned so the drugs they carry are released at different rates, allowing them to be tailored for different uses.

The researchers are now looking into using the gel to deliver anti-angiogenesis drugs to treat macular degeneration. Currently, patients receive these drugs, which cut off the growth of blood vessels that interfere with sight, as an injection into the eye once a month. The MIT team envisions that the new gel could be programmed to deliver these drugs over several months, reducing the frequency of injections.

Another potential application for the gels is delivering drugs, such as growth factors, that could help repair damaged heart tissue after a heart attack. The researchers are also pursuing the possibility of using this gel to deliver cancer drugs to kill tumor cells that get left behind after surgery. In that case, the gel would be loaded with a chemical that lures cancer cells toward the gel, as well as a chemotherapy drug that would kill them. This could help eliminate the residual cancer cells that often form new tumors following surgery.

"Removing the tumor leaves behind a cavity that you could fill with our material, which would provide some therapeutic benefit over the long term in recruiting and killing those cells," Appel says. "We can tailor the materials to provide us with the drug-release profile that makes it the most effective at actually recruiting the cells."

New Neuropathy Uses For Old Drugs

Today's short post from fiercebiotech.com (see link below) looks at so-called antimuscarinic drugs, currently used in the treatment of a range of conditions from incontinence to ulcers. Researchers have found that these drugs can block receptors which effectively block nerve regeneration, thus extending and increasing the effects of nerve damage. Antimuscarinic drugs block this action and therefore allow nerve regeneration (at least in mice). With me so far? Possibly not but basically it means that nerve receptors that prevent nerves from re-growing after damage (leading to the lifelong pain most of you feel) can be themselves blocked by drugs currently used for other conditions. Nothing new in the neuropathy world here then - most of the drugs we take to dampen our symptoms, are already used for other things and we suffer the side effects as a result. However, this looks promising because if damaged nerves can be allowed to repair themselves, then the symptoms will theoretically reduce considerably. Hope springs eternal!

Peripheral neuropathy could be reversed by FDA-approved class of drugs
by Amirah Al Idrus Jan 19, 2017 

Scientists from the University of Manitoba and UCSD found that a class of already-approved drugs reversed peripheral neuropathy in mouse models.

Treatments for peripheral neuropathy, the numbness and pain most commonly felt in the fingers, arms and legs due to nerve damage, tend to focus on managing pain. But an international team may have found an alternative approach that could potentially reverse symptoms with a class of drugs already in use for other conditions.

Addressing the underlying condition behind neuropathy—such as diabetes—is a major part of alleviating symptoms, but there is no approved treatment that focuses on nerve degeneration. While studying mechanisms involved in neuron growth and regrowth, scientists from UC San Diego and the University of Manitoba, alongside colleagues from St. Boniface Hospital and the National Institute of Diabetes and Digestive and Kidney Diseases, identified a pathway that stunts the outgrowth of neurites, which connect neurons to other neurons.

The activation of muscarinic acetylcholine receptors inhibits the growth of sensory neurons. The team found that blocking this pathway reversed the effects of peripheral neuropathy in mouse models of Type 1 and 2 diabetes, HIV and chemotherapy-induced neuropathy. Their findings were published in the Journal of Clinical Investigation.

The best part? A number of antimuscarinic drugs, such as atropine and pirenzepine, are already approved and on the market for other indications, ranging from incontinence to peptic ulcers. This could lead to a potentially speedy path to clinical use.

Paul Fernyhough of the University of Manitoba and St. Boniface Hospital, Nigel Calcutt of UC San Diego and Lakshmi Kotra of the University of Toronto have cofounded the company WinSanTor to continue working on this approach.

The biotech has exclusively licensed the technology from the researchers and has come up with a repurposed and reformulated version of an already-approved drug, dubbed WST-057. The candidate has prevented and reversed nerve fiber depletion and sensory loss in animal models of peripheral neuropathy, according to a statement.

“An exciting aspect of this work is that these are new uses for old drugs. They have been used in humans for over 20 years with no serious side effects and have an excellent safety profile. We expect Phase 1 trials to progress smoothly with Phase 2 trials arranged and already funded for 2017,” said Fernyhough in a statement.

http://www.fiercebiotech.com/research/peripheral-neuropathy-could-be-reversed-by-fda-approved-class-drugs

NEW HORIZON IN HEART FAILURE INVESTIGATIONAL DRUG POISED TO CHANGE CARDIOLOGY

An investigational new heart failure drug could be poised to change the face of cardiology based on Hot Line results presented today at ESC Congress 2014

Findings from the PARADIGM-HF trial, published simultaneously in the New England Journal of Medicine, "are extraordinarily powerful and compelling; they are destined to change the management of patients with chronic heart failure for years to come," said Milton Packer, MD, co-primary author of the study from University of Texas Southwestern Medical Center, in Dallas, Texas USA.

"This really is an astonishing result and a real breakthrough for patients with heart failure," added John McMurray, MD, the other co-primary author, from the University of Glasgow, UK.

The new agent, an angiotensin receptor-neprilysin inhibitor (ARNI) known as LCZ696, has already been granted Fast Track status by the United States Food and Drug Administration (FDA) -- a designation which can expedite the review of new medicines intended to treat serious or life-threatening conditions. Fast Track designation also allows for rolling submission in the US, which Novartis said it expects to complete by the end of 2014. The company said it aims to file in Europe in early 2015.

"To say that we are excited is an understatement. We are absolutely thrilled," said Dr. Packer.

"Given the survival advantage of LCZ696 over currently available drugs, once this drug becomes available, it would be difficult to understand why physicians would continue to use traditional angiotensin converting-enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) for the treatment of heart failure."

PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) first made headlines this spring when the trial was stopped early by an independent data monitoring committee based on evidence of the "overwhelming benefit" of LCZ696 compared to enalapril, an ACE inhibitor.

"We were surprised and delighted that the magnitude of the superiority was so great that the trial was stopped early by the ethical committee. That was an amazing event," said Dr. Packer.

Today, full details of the findings are being released for the first time.

"The magnitude of the advantage of LCZ696 over enalapril on cardiovascular mortality was at least as large as that of enalapril over placebo during long-term treatment," Dr. Packer reported. "This robust finding provides strong support for using this new approach instead of ACE inhibitors or ARBs in the treatment of chronic heart failure."

PARADIGM-HF randomized 8,399 patients with class II to IV heart failure and an ejection fraction if 40% or less to either LCZ696 200 mg twice daily (n=4,187), or enalapril 10 mg twice daily (n=4,212), in addition to recommended therapy.

When the trial was stopped early, after a median follow-up of 27 months, death from cardiovascular causes or hospitalisation for heart failure (the primary composite outcome) had occurred in 21.8% of the LCZ696 group and 26.5% of the enalapril group (hazard ratio [HR] 0.80; p=0.0000002).

Compared to enalapril, LCZ696 reduced the risk of death from cardiovascular causes by 20% (13.3% vs 16.5%; HR 0.80; p<0.0001), and the risk of hospitalisation for heart failure by 21% (12.8% vs 15.6%; HR 0.79; p<0.0001), noted Dr. Packer. This effect was consistent across all prespecified subgroups.

Secondary outcomes were also significantly improved by LCZ696, including all-cause mortality (17.0% vs 19.8%; HR 0.84; p<0.001) and symptoms and physical limitations of heart failure measured on the Kansas City Cardiomyopathy Questionnaire (p=0.001).

"The superiority of LCZ696 over enalapril was not accompanied by important safety concerns," added Dr. Packer. The LCZ696 group had more symptomatic hypotension compared to the enalapril group (14% vs 9.2%, p< 0.001) however this rarely required the discontinuation of treatment. In fact, fewer patients in the LCZ696 group stopped their study medication for any adverse event (10.7% vs 12.3%, P=0.03).

Importantly, LCZ696 was not associated with an increased risk of serious angioedema, which was the main safety concern observed with a related medication -- omapatrilat -- in the OVERTURE trial.

Omapatrilat's association with life-threatening angioedema is related to its inhibition of ACE, neprilysin and aminopeptidase P, whereas LCZ696 avoids inhibition of ACE and aminopeptidase P. "LCZ696 was specifically designed to minimise the risk of serious angioedema by combining the neprilysin inhibitor sacubitril (AHU377) and the ARB valsartan," explained Dr. Packer.

Findings of the PARADIGM-HF trial are particularly striking when considered in the context of the current standard of care in heart failure, concluded Professor McMurray.

"The superiority of LCZ696 wasn't over placebo -- it was over the gold-standard dose of the gold-standard ACE inhibitor, the absolute corner-stone of guideline-recommended, conventional therapy," he said. "On top of that, these incremental benefits were obtained in patients fully treated with the other key pharmacological therapies for this condition such as beta-blockers and mineralocorticoid receptor antagonists. All that you can ask of any new therapy in heart failure (or other chronic diseases) is to make patients live longer, stay out of hospital and feel better -- and those are exactly the benefits we demonstrated with LCZ696."

Spring Peeks Baby Nettles Monarda and the Littles of the New Season

Spring Peeks

The newest greens of the Equinox!

March 22, 2012 Newsletter

Enjoy! 

xoxox

New Discovery Curbs Nerve Pain Without Drug Side Effects

Today's post from sciencedaily.com (see link below) is one of those complex technical ones that often leave us scratching our heads to wonder how it could possible affect our own personal situations. However, if you take a little time to read it, you should get the gist of what it's saying and what the implications are. It starts off with a neuropathy-patient-friendly call for treatments that work well on people and not just laboratory mice. We are so used to the newest developments being announced at the rodent-testing stage, that we lose faith that they will ever be translated to human treatment. This article tries to show that the gulf between lab-rats and humans in this case, is not so large after all. Worth a read.

Potent approach shows promise for chronic pain
Inhibitor discovered through human, mouse genetic studies curbs pain without narcotic side effects 
Date:June 17, 2015 Source:Boston Children's Hospital

Non-narcotic treatments for chronic pain that work well in people, not just mice, are sorely needed. Drawing from human pain genetics, an international team led by Boston Children's Hospital demonstrates a way to break the cycle of pain hypersensitivity without the development of addiction, tolerance or side effects.

Their findings, reported June 17 in the journal Neuron, could lead to treatments for chronic pain conditions caused by nerve damage, such as diabetic peripheral neuropathy (DPN) and post-herpetic neuralgia (PHN), as well as chronic inflammation, like rheumatoid arthritis. Current treatments provide meaningful pain relief in only about 15 percent of patients.

"Most pain medications that have been tested in the past decade have failed in phase II human trials despite performing well in animal models," notes Clifford Woolf, MD, PhD, director of Boston Children's F.M. Kirby Neurobiology Center and a co-senior investigator on the study with Michael Costigan, PhD. "Here, we used human genetic findings to guide our search from the beginning."

In 2006, Costigan, Woolf and colleagues showed in Nature Medicine that people with variants of the gene for GTP cyclohydrolase (GCH1)--about 2 percent of the population--are at markedly lower risk for chronic pain. GCH1 is needed to synthesize the protein tetrahydrobiopterin (BH4), and people with GCH1 variants produce less BH4 after nerve injury. This suggested that BH4 regulates pain sensitivity.

"We wanted to use pharmacologic means to get the same effect as the gene variant," says Alban Latremoliere, PhD, also of Boston Children's Kirby Center, who led the current study along with Woolf and Costigan.

In a "reverse engineering" approach, the researchers modeled the human biology in mice. They first showed that mice with severed sensory nerves produce excessive BH4, churned out both by the injured nerve cells themselves and by macrophages--immune cells that infiltrate damaged nerves and inflamed tissue. Mice engineered to make excess BH4 had heightened pain sensitivity even when they were uninjured, suggesting that BH4 is sufficient to produce pain. On the flip side, mice that were genetically unable to produce BH4 in their sensory nerves had decreased pain hypersensitivity after peripheral nerve injury.

"We then asked, if we could reduce production of BH4 using a drug, could we bring about reduction of pain?" says Latremoliere.

The answer was yes. The researchers blocked BH4 production using a specifically designed drug that targets sepiapterin reductase (SPR), a key enzyme that makes BH4. The drug reduced the pain hypersensitivity induced by the nerve injury (or accompanying inflammation) but did not affect nociceptive pain--the protective pain sensation that helps us avoid injury.

Fine-tuning pain relief

Because BH4 is active all over the body, with important roles in the brain and blood vessels, the goal of any treatment would be to dial down excessive BH4 production, but not eliminate it entirely. Latremoliere and colleagues showed that blocking SPR still allowed minimal BH4 production through a separate pathway and reduced pain without causing neural or cardiovascular side effects.

"Our findings suggest that SPR inhibition is a viable approach to reducing clinical pain hypersensitivity," says Woolf. "They also show that human genetics can lead us to novel disease pathways that we can probe mechanistically in animal models, leading us to the most suitable targets for human drug development."

Story Source:

The above post is reprinted from materials provided by Boston Children's Hospital. Note: Materials may be edited for content and length.

Journal Reference:
Clifford J. Woolf et al. Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway. Neuron, June 2015 DOI: 10.1016/j.neuron.2015.05.033

http://www.sciencedaily.com/releases/2015/06/150617135409.htm

IMMUNE SYSTEM OF NEW BORN BABIES STRONGER THAN PREVIOUSLY THOUGHT

Contrary to what was previously thought, newborn immune T cells may have the ability to trigger an inflammatory response to bacteria, according to a new study led by King's College London. Although their immune system works very differently to that of adults, babies may still be able to mount a strong immune defense, finds the study published in the journal Nature Medicine.

Our immune system is made up of several different types of immune cells, including neutrophils which play an important role in the frontline defense against infection, and lymphocytes: B cells which produce antibodies, and T cells that target cells infected with viruses and microbes.

Up to now, it was generally believed that babies have an immature immune system that doesn't trigger the same inflammatory response normally seen in adults. Although babies need to protect themselves from the harmful pathogens they are exposed to from birth, it was thought that their T cells were suppressed to some extent to prevent inflammatory damage to the developing child. Sceptical of this notion, the King's-led study set out to characterize the properties of T cells, examining very small samples of blood in twenty-eight highly premature babies, as they developed over the first few weeks of life.

The team discovered that whilst T cells in newborn babies are largely different to those in adults, it is not because they are immunosuppressed; rather, they manufacture a potent anti-bacterial molecule known as IL8 that has not previously been considered a major product of T cells, and that activates neutrophils to attack the body's foreign invaders.

Dr Deena GibbonsDeena Gibbons, lead author in the Department of Immunobiology at King's College London, says: "We found that babies have an in-built anti-bacterial defense mechanism that works differently to adults, but nevertheless may be effective in protecting them. This may also be a mechanism by which the baby protects itself in the womb from infections of the mother. The next stage of our work will be to better understand the pathways that result in the immune cells of newborns being so different to those in adults."

This T cell activity could become a target for future treatments aimed at boosting the immune system of neonates in intensive care, where infection is a major risk for morbidity and mortality. Premature babies are also at serious risk of developing inflammatory diseases such as necrotising enterocolitis (NEC), where severe inflammation destroys tissues in the gut. NEC is the most common gastrointestinal surgical emergency in preterm babies, with mortality rates of around 15 to 30 per cent in the UK.

New FDA Rules For Gluten Free Labelling

Today's post from prevention.com (see link below) is another article looking at gluten free diets and what this exactly entails. The American FDA has done us a favour by stepping in to regulate the gluten 'industry' so that the term 'gluten free' genuinely means what it says. This of course doesn't mean that all countries are as well-regulated but it's a guide and when the FDA decides to act, the rest of the world generally follows soon after. That said, the hype that gluten-free is beneficial for the nervous system and neuropathy problems is exactly that - hype and nothing has been proved. There is no doubt however, that many people claim to have benefited from changing to gluten-free. It's not easy and can lead to a 'boring' diet but it may be worth doing the research and consulting your doctor to see if it's an option for you.

What The FDA's New "Gluten-Free" Label Really Means 
By Robin Hilmantel for Women's Health Published August 2014,

If you've been buying foods labeled "gluten-free," we have some good news and some bad news for you. The bad news: Nothing you've bought up until this point has had to adhere to a uniform standard of what it actually means to be "gluten-free." The good news? As of August 2, there's finally a definition to go along with the label.

MORE: Are Gluten-Free Diets Healthy?

Late last week, the FDA published a new regulation defining the term. To be considered "gluten-free," a product now must contain less than 20 parts per million of gluten. Products bearing the labels "free of gluten," "no gluten," and "without gluten" are also now required to meet this standard.

“Adherence to a gluten-free diet is the key to treating celiac disease, which can be very disruptive to everyday life,” FDA Commissioner Margaret A. Hamburg, M.D., said in a press release. “The FDA’s new ‘gluten-free’ definition will help people with this condition make food choices with confidence and allow them to better manage their health.”

MORE: Gluten-Free Foods That Make You Gain Weight

One word of warning: Food manufacturers have until August 2, 2015, to bring their products into compliance with this new criteria. Granted, some products on the market may already meet this standard (and items that have less than 20 parts per million of gluten aren't required to be listed as "gluten-free;" it's a voluntary label).

Even after companies are required to comply with the new ruling, they can still use the terms "made with no gluten-containing ingredients" or "not made with gluten-containing ingredients" on products that don't fit the definition of "gluten-free" (provided these other labels are true). The bottom line? Even with the new regulation, it's still a good idea to reach out to the company or restaurant making a food if you have any questions about how much gluten it might contain.

http://www.prevention.com/food/healthy-eating-tips/fda-changes-gluten-free-labeling

Gluten Intolerance And Neuropathy New Findings

Today's post from techtimes.com (see link below) is the latest article linking gluten intolerance (celiac disease) to neuropathy. You may have read various articles from various sources, recommending reducing gluten in your diet if you have neuropathic problems. Quite often, dramatic results can be achieved when people exclude gluten from their food intake. However, it's by no means a universal truth and certainly not a scientific fact...yet. So what should you do? It's probably best to do as much research as possible via reliable sites on the question and discuss it carefully with your doctor (although most doctors aren't sure either). A gluten-free diet seems to have several benefits but is extremely difficult (and often boring!) to implement.
 

Celiac Disease Linked To Nerve Disease In Neuropathy Patients - Is Gluten To Blame?
By James Maynard, Tech Times | May 12, 8:27 AM

Gluten Intolerance could be tied to nerve damage. Should you be worried?

Celiac disease appears to be linked to nerve damage known as neuropathy.

Researchers examined medical records of over 28,000 patients with celiac disease as well as 139,000 people who were never diagnosed with the disorder. They found that those patients with the condition were 2.5 times as likely as the control group to suffer from nerve damage.

Celiac disease, also known as gluten intolerance, is a digestive disorder that causes pain and discomfort to sufferers when they consume the protein composite. This autoimmune response can reduce the efficiency of food absorption and can damage the linings of small intestines. Roughly 1 percent of all Americans suffers from gluten intolerance, regardless of race or gender.

The idea that the two medical conditions could be linked goes back about five decades, although this new study is the most-detailed investigation yet done of the idea.

Despite the apparent strong correlation between neuropathy and celiac disease, the total numbers of patients still remains low enough that a definite correlation between the two conditions cannot be proven. Neuropathy was seen in 0.3 percent of patients in the control group and 0.7 percent of people with celiac disease. There was no apparent difference in the possible correlation of the two conditions detected between men and women.

"We found an increased risk of neuropathy in patients with CD [celiac disease] that persists after CD diagnosis. Although absolute risks for neuropathy are low, CD is a potentially treatable condition with a young age of onset. Our findings suggest that screening could be beneficial in patients with neuropathy," researchers wrote in an article detailing their study.

According to the National Foundation for Celiac Awareness, roughly 83 percent of people suffering from CD are not diagnosed, or their health care provider believes their symptoms are attributable to other causes. Patients can often wait between six and 10 years before they are properly diagnosed with the disorder. Celiac disease can also lead to other autoimmune diseases, neurological disorders, reduced bone density and even some forms of cancer. There are no known treatments for the condition, leaving patients with little choice except to remove gluten — which gives dough its elasticity — from their diets.

Neuropathy is a medical term used for many different forms of nerve damage, although it usually refers to nerves outside the central nervous system. Such damage can be brought on from a number of causes, including infection, physical trauma or chemical influences. Many forms can be treated through therapy and drugs.

Analysis of the possible association of celiac disease with neuropathy was profiled in the journal Jama Neurology.

http://www.techtimes.com/articles/52228/20150512/celiac-disease-linked-to-nerve-disease-in-neuropathy-patients-is-gluten-to-blame.htm

New Research Into Healing Nerve Damage

Today's article from neurologywestla.com (see link below) is another interesting piece of research that is years away from being applicable to patients but is nevertheless evidence of the new impetus in nerve damage research that can only be good for the future. It talks about the discovery of a protein (Retinoblastoma) which is present in nerve cells. This protein normally acts as a 'stopper' to nerve growth. It's thought that by inactivating this protein in some way, damaged nerves will be able to regenerate and grow again. That of course is a very simplistic summary and the research is still at an early stage where it's being carried out on animals. However, most people will get the idea and be able to follow the logic. Now we have to wait ten years until it's proved to be a successful process in humans.

Peripheral Neuropathy And Injuries Causing Nerve Damage May Be Healed With New Technique
New Technique for Peripheral Neuropathy
By Susan Scutti | Apr 22, 2014
Posted by npatel on May 1, 2014 

Canadian scientists discovered a crucial molecule, a protein called Retinoblastoma (Rb), that directly regulates nerve cell growth and may be helpful someday in healing peripheral neuropathy.

Many people with diabetes experience neuropathy, a painful form of nerve damage that cannot always be treated effectively with drugs. In their research of the condition, scientists at University of Calgary’s Hotchkiss Brain Institute discovered a mechanism that promotes growth in damaged nerve cells. In fact, the team of researchers discovered a crucial molecule that directly regulates nerve cell growth. “We made the surprising discovery that a protein called Retinoblastoma (Rb) is present in adult neurons,” said Dr. Doug Zochodne, a professor in the Department of Clinical Neurosciences, and author of the study. “This protein appears to normally act as a brake — preventing nerve growth. What we have shown is that by inactivating Rb, we can release the brake and coax nerves to grow much faster.”

Neuropathy, which creates a tingling or burning sensation, is a direct result of nerve damage. Peripheral nerves, which connect the brain and spinal cord to the body, help us feel sensation and also enable movement. Peripheral neuropathy, which causes numbness and pain in your hands and feet, may be the result of any number of factors, including injuries, infections, and even exposure to toxins. Cancer patients, for instance, experience peripheral neuropathy during or following toxic chemotherapy. About 60 to 70 percent of people with diabetes also encounter this condition, with the risk rising with age and duration of their illness. All too common, diabetic neuropathy is more prevalent than multiple sclerosis, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS) combined. Although for some people, the symptoms of peripheral neuropathy may improve over time, this is not the case for all and for this reason, researchers would like to understand how exactly it works.

Based on his understanding of cancer, Zochodne and his research team decided to look for Retinoblastoma in nerve cells. “We know that cancer is characterized by excessive cell growth and we also know that Rb is often functioning abnormally in cancer,” explained Zochodne in a press release. “If cancer is able to release this brake and increase cell growth, we thought we’d try to mimic this same action in nerve cells and encourage growth where we want it,” he said.

In their experiments using cells and animals, the researchers shut down Retinoblastoma in the peripheral nervous system for a short span of time and carefully observed the results. As hypothesized, they saw new growth without any apparent negative effects. Now, they are wanting to advance their experiments to the point of working with humans and in so doing, they hope their work may lead to safe treatments for patients suffering from neuropathy and other forms of nerve damage.

Source: Christie KJ, Krishnan A, Zochodne D, et al. Enhancing adult nerve regeneration through the knockdown of retinoblastoma protein. Nature Communications. 2014.

http://neurologywestla.com/peripheral-neuropathy-and-injuries-causing-nerve-damage-may-be-healed-with-new-technique/

New Repair Technique For Nerve Injuries

Today's post from sciencedaily.com (see link below) talks about advances in nerve repair after injury, where the nerve is severed in some way. Many people suffer neuropathy from direct injury to the nerve, thanks to some sort of accident. In the past, nerve transplants or grafts have been possible in some cases but are fraught with problems and the chances of infection and rejection. The process has recently been refined by using nerves taken from cadavers (corpses). These are processed to remove all cellular material whilst preserving their integrity and this means a lesser chance of infection. These nerve grafts (called allografts) are proving far more efficient in nerve gap repair and the chances of nerve regeneration are far higher.
This is only applicable to those people who suffer nerve damage through injury and accident.

Promise for new nerve repair technique
 August 8, 2014  University of Kentucky 

Summary:

A new nerve repair technique yields better results and fewer side effects than other existing techniques, research shows. Traumatic nerve injuries are common, and when nerves are severed, they do not heal on their own and must be repaired surgically. Injuries that are not clean-cut -- such as saw injuries, farm equipment injuries, and gunshot wounds -- may result in a gap in the nerve.
 
A multicenter study including University of Kentucky researchers found that a new nerve repair technique yields better results and fewer side effects than other existing techniques.

Traumatic nerve injuries are common, and when nerves are severed, they do not heal on their own and must be repaired surgically. Injuries that are not clean-cut -- such as saw injuries, farm equipment injuries, and gunshot wounds -- may result in a gap in the nerve.

To fill these gaps, surgeons have traditionally used two methods: a nerve autograft (bridging the gap with a patient's own nerve taken from elsewhere in the body), which leads to a nerve deficit at the donor site; or nerve conduits (synthetic tubes), which can cause foreign body reactions or infections.

The prospective, randomized study, conducted by UK Medical Director of Hand Surgery Service Dr. Brian Rinker and others, compared the nerve conduit to a newer technique called a nerve allograft. The nerve allograft uses human nerves harvested from cadavers. The nerves are processed to remove all cellular material, preserving their architecture while preventing disease transmission or allergic reactions.

Participants with nerve injuries were randomized into either conduit or allograft repair groups. Following the surgeries, independent blind observers performed standardized assessments at set time points to determine the degree of sensory or motor recovery.

The results of the study suggested that nerve allografts had more consistent results and produced better outcomes than nerve conduits, while avoiding the donor site morbidity of a nerve autograft.

Rinker, a principal investigator of the study, describes it as a "game-changer."

"Nerve grafting has remained relatively unchanged for nearly 100 years, and both of the existing nerve repair options had serious drawbacks," Rinker said. "Our study showed that the new technique processed nerve allograft ­- provides a better, more predictable and safer nerve gap repair compared to the previous techniques."

Rinker also noted that work is underway to engineer nerve allografts with growth factors which would guide and promote nerve regeneration, theoretically leading to even faster recoveries and better results.

Story Source:

The above story is based on materials provided by University of Kentucky. Note: Materials may be edited for content and length. 

http://www.sciencedaily.com/releases/2014/08/140808163451.htm