Clinical Trial

(cenksns/Shutterstock) We Finally Know How Our Immune Cells Remember Diseases For So Long

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For many of us, remembering faces from 30 years ago can be something of a challenge. But cells in our immune system can remember old foes just fine, and we’ve never really been sure exactly how they manage it.

A new study has filled in missing details on the steps our body takes to remember pathogens, finally revealing the steps our immune cells take to preserve a reference library of past battles.

Scientists from the University of California, Berkeley, used a hydrogen isotope to label white blood cells inside volunteers, and tracked a specially selected virus from infection to immunity in order to record significant steps in the immune process.

The big picture of adaptive immunity and our ability to remember and eliminate specific pathogens has gradually built up over the past century.

We have different types of white blood cell that help spot and destroy invading cells. Two of these are B cells, which make and secrete antibodies to act as ‘name tags’ for the bad guys, and T cells, which perform a bunch of immune-related tasks such as recognising the foreign invaders.

Both include cell types that act as cellular historians, preserving remnants of past battles like old veterans.

Exactly how our immune cells do their job of identifying and then recording these events – at least on a chemical level – is where the story gets vague.

“This work addressed fundamental questions about the origin and longevity of human memory CD8+ T cells generated after an acute infection,” says senior author and nutritionist Marc Hellerstein from UC Berkeley.

Cytotoxic ‘CD8+’ T cells are a form of cellular assassin, raised in the body’s thymus to recognise familiar cells before being released to find unfamiliar fiends – such as cancer cells, bacteria, or cells infected with viruses.

On finding them, the body encourages these special T cells to proliferate. The small army releases chemicals into the enemy cells, punching holes in their membranes and destroying them.

Not all cytotoxic T cells go into battle to die glorious deaths taking down the enemy, though. Some stick around, and appear to be responsible for mounting quicker attacks should the tumours or pathogens return.

To get to the bottom of this process, the researchers gave 40 volunteers water that contained deuterium instead of standard hydrogen, which marked out any new cells they produced in their body at different intervals.

They then vaccinated them with an attenuated live yellow fever vaccine – a virus that the volunteers shouldn’t encounter in their home environment.

With the new CD8+ T cells readily identifiable, the researchers were able to track the cells over coming months to gain an idea of how their numbers and chemical make-up changed.

They discovered that after the initial response to the vaccination, a pool of memory cells forms. These cells look and behave more like naive cytotoxic T cells, with one difference; their genes are tagged epigenetically with the memories of war.

“These cells are like veteran soldiers, camped in the blood and tissues where they fight their battles, waiting for yellow fever to show up,” says Hellerstein.

“They are resting quietly and they wear the clothes of untested new recruits, but they are deeply experienced, ready to spring into action and primed to expand wildly and attack aggressively if invaders return.”

This quiescent state is the secret to their success, allowing them to quietly lurk in the background, ready to shift into high gear and attack the moment the pathogen returns.

On average, T cells have a half-life of about 30 days, meaning after a month most of the white cells have died. These disguised veteran T cells have a half-life of 450 days, meaning some of them can stick around for years, if not decades.

And the more we know about the memory system of our immune cells, the better we can use it to our advantage.

“Understanding the basis of effective long-term immune memory may help scientists develop better vaccines, understand differences among diseases and diagnose the quality of an individual person’s immune responses,” says Hellerstein.

This research was published in Nature.

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USFDA approves first drug for Eosinophilic Granulomatosis with Polyangiitis, a rare disease formerly known as the Churg-Strauss Syndrome

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The U.S. Food and Drug Administration today expanded the approved use of Nucala (mepolizumab) to treat adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), a rare autoimmune disease that causes vasculitis, an inflammation in the wall of blood vessels of the body. This new indication provides the first FDA-approved therapy specifically to treat EGPA.

According to the National Institutes of Health, EGPA (formerly known as Churg-Strauss syndrome) is a condition characterized by asthma, high levels of eosinophils (a type of white blood cell that helps fight infection), and inflammation of small- to medium-sized blood vessels. The inflamed vessels can affect various organ systems including the lungs, gastrointestinal tract, skin, heart and nervous system. It is estimated that approximately 0.11 to 2.66 new cases per 1 million people are diagnosed each year, with an overall prevalence of 10.7 to 14 per 1,000,000 adults.

“Prior to today’s action, patients with this challenging, rare disease did not have an FDA-approved treatment option,” said Badrul Chowdhury, M.D., Ph.D., director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research. “The expanded indication of Nucala meets a critical, unmet need for EGPA patients. It’s notable that patients taking Nucala in clinical trials reported a significant improvement in their symptoms.”

The FDA granted this application Priority Review and Orphan Drug designations. Orphan Drug designation provides incentives to assist and encourage the development of drugs for rare diseases.

Nucala was previously approved in 2015 to treat patients age 12 years and older with a specific subgroup of asthma (severe asthma with an eosinophilic phenotype) despite receiving their current asthma medicines. Nucala is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa) produced by recombinant DNA technology in Chinese hamster ovary cells.

Nucala is administered once every four weeks by subcutaneous injection by a health care professional into the upper arm, thigh, or abdomen.

The safety and efficacy of Nucala was based on data from a 52-week treatment clinical trial that compared Nucala to placebo. Patients received 300 milligrams (mg) of Nucala or placebo administered subcutaneously once every four weeks while continuing their stable daily oral corticosteroids (OCS) therapy. Starting at week four, OCS was tapered during the treatment period. The primary efficacy assessment in the trial measured Nucala’s treatment impact on disease remission (i.e., becoming symptom free) while on an OCS dose less than or equal to 4 mg of prednisone. Patients receiving 300 mg of Nucala achieved a significantly greater accrued time in remission compared with placebo. A significantly higher proportion of patients receiving 300 mg of Nucala achieved remission at both week 36 and week 48 compared with placebo. In addition, significantly more patients who received 300 mg of Nucala achieved remission within the first 24 weeks and remained in remission for the remainder of the 52-week study treatment period compared with patients who received the placebo.

The most common adverse reactions associated with Nucala in clinical trials included headache, injection site reaction, back pain, and fatigue.

Nucala should not be administered to patients with a history of hypersensitivity to mepolizumab or one of its ingredients. It should not be used to treat acute bronchospasm or status asthmaticus. Hypersensitivity reactions, including anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash, have occurred. Patients should discontinue treatment in the event of a hypersensitivity reaction. Patients should not discontinue systemic or inhaled corticosteroids abruptly upon beginning treatment with Nucala. Instead, patients should decrease corticosteroids gradually, if appropriate.

Health care providers should treat patients with pre-existing helminth infections before treating with Nucala because it is unknown if Nucala would affect patients’ responses against parasitic infections. In addition, herpes zoster infections have occurred in patients receiving Nucala. Health care providers should consider vaccination if medically appropriate.

The FDA granted approval of Nucala to GlaxoSmithKline.

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Our Sense of Smell Provides a New Way to Battle Spinal Cord Injuries

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Two Treatments Combined

Researchers from the University of Bristol have just shared the promising results of a new treatment for spinal cord injuries that could help regenerate nerves and potentially improve patients’ quality of life.

The new therapy involves the transplantation of cells that have been modified to secrete a molecule that helps to remove scarring caused by spinal cord damage. This scarring can limit the regrowth of nerves, thus greatly hindering a patient’s potential for recovery.

Previous studies have shown that the enzyme chondroitinase ABC (ChABC) is effective at promoting nerve regrowth when used as a part of drug therapies for spinal injuries. Unfortunately, the enzyme does not have a long life once injected. That means patients must be subjected to repeated treatments for the enzyme to be effective.

Olfactory ensheathing cells have the ability to regenerate and repair themselves over the course of a person’s life in order to maintain the sense of smell. That ability makes these cells ideal for genetic modification when the goal is prolonging a molecule’s lifespan.

This new treatment from the University of Bristol team utilizes this ability of the olfactory cells to prolong the secretion of ChABC for the treatment of spinal cord injuries.

For their study, which has been published in PLOS ONE, the researchers injected mice with canine olfactory ensheathing cells that had been genetically modified to secrete ChABC. After transplantation, they observed the successful secretion of ChABC as well as the removal of some scarring. They also noted signs of successful nerve regeneration.

It is an important proof-of-concept for this revolutionary treatment method, but more testing is needed to determine effectiveness.

“While these initial results look promising, in order to determine the longer-term survival of our genetically modified cells and assess functional recovery, such as recovery of walking or recovery of continence, we need to carry out further studies to test these cell transplants in more chronic injury models,” Liang-Fong Wong, Senior Lecturer at Bristol Medical School and part of the study’s team, said in a news release.

If future tests in mice go as hoped, the treatment can then be adapted for other animals and, eventually, humans.

Renewed Hope

An increasing number of potential treatments to help restore lost functionality after a spinal cord injury are in the works, and while many of these solutions hold great promise, more testing is needed to prove their efficacy and safety.

Still, scientific innovation in fields such as neuroscience, medicine, and even robotics is giving victims of spinal cord injuries renewed hope of recovery.

Researchers out of the University of Louisville’s Kentucky Spinal Cord Injury Research Center (KSCIRC) have recently restored voluntary movement in a 28-year-old patient who suffered a spinal cord injury from a motorcycle accident. His treatment combined new technology with established science — electric stimulation through an implant on the spine and traditional rehabilitation techniques — to deliver potentially life-changing results.

Meanwhile, a promising therapy from Rush University Medical Center was able to restore motor function in four out of six paralyzed patients. That cell therapy builds on decades of stem cell research, a promising area of study for spinal injury treatments.

Studies like these can be a great source of hope for both those living with spinal injuries and their loved ones. While it may be quite a long time before these treatments are proven to live up to their lofty promise, the goal of ending the ability of a single devastating moment to put mobility in a stranglehold is a fierce motivator.

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National signature campaign launched to bring glucometer strips under price control as per DPCO norms

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Aimed at making glucometer strips affordable for all diabetes patients, over 15,000 petitions have been signed till date as part of the national signature campaign under the auspices of Dr Gadage’s Diabetes Care Centre, Mumbai called as Price Ceiling Gluco Strips Petition.

“Post the signature campaign which started on World Diabetes Day on November 14, 2017, the case of overpriced Glucometer strips will be discussed with the drug pricing regulator National Pharmaceutical Pricing Authority (NPPA) to bring it under the ceiling prices as per the Drug Price Control Order (DPCO) norms,” said Dr Pradeep Gadge, Diabetologist, Gadge Diabetes Centre.

Glucometer strips is one of the major recurring cost in regular monitoring of diabetes cost of which is further compounded as most companies charge Rs.20 to Rs.25 per glucometer strip. The cost to the patient is therefore exorbitantly high compared to the production cost which is roughly 50 paise per strip.

The reduction in the prices of glucometer strips shall ensure slight relief from the financial burden and help diabetics manage their blood glucose levels well.

“The cost of healthcare is drastically increasing, the manufacturing cost of a Glucostrip is 50 paise but the patient is charged Rs.25 to Rs.30. Those who need to keep a check on their Blood Glucose levels for more than once in a day will have to shell out around Rs.500 a day which may not be feasible for all. Especially if one keeps in mind the prevalence of diabetes in the country. The need of the hour is price ceiling of Glucostrips, this will help make it affordable for all,” added Dr Gadge.

According to a senior health ministry official which was part of the drafting committee of Uniform Code for Medical Device Marketing Practices (UCMDMP), “All such technologies which are closed systems like the Glucometer for which the patient has to buy the reagents of a particular brand can be given or considered as induced in turn incentive to the physician. If a company gifts the doctor a Glucometer, he will be forced to buy and then recommend the strips of the same Glucometer although the Glucometer was free. So in a way the company and the doctor are distorting the market.”

Moreover, there are Glucometers in the market which are of low quality and sub-standard nature that it is detrimental to patient safety as it can lead to improper diagnosis.

Millions of diabetics spend a substantial amount of their earnings on testing their blood glucose levels. The number of petitioners continues to increase with each passing day as this has turned up to be the need of the hour.

Although government has recently introduced the DPCO – 2013 which has helped reduce the prices of many medications, there has been no respite for Diabetics. Those with Type I Diabetes may have to check their blood glucose levels for around 3 to 4 times a day. With such steep pricing, it becomes difficult to bear the expenses.

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Scientists Discover Plants Respond to Anesthetics — Which Could End Animal Testing

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Anesthetic Testing

First used as an alternative to crude methods like alcohol in the 19th century, anesthetics have become a critical part of medical systems around the world. Currently, anesthetics are tested on animals, which is ethically questionable and can produce ineffective results. But one new study could forever change how we test these drugs. Researchers recently found that plants respond to anesthetics the same way to that humans and animals do.

This research explored these effects in Mimosa leaves, pea tendrils, Venus flytraps, and sundew traps. When Venus flytraps were exposed to anesthetics, they stopped generating electrical signals; even when trigger hairs were touched, their traps stayed open. Similarly, pea tendrils were stuck into a spiraled shape upon exposure, and they completely stopped all autonomous movement. In all of these plant species, the anesthetic caused the plant to lose both autonomous and touch-based movement.

This study has furthered our understanding of how exactly anesthetic affects living organisms and their functionality. Practically speaking, this could push scientists to test anesthetics in plants over animal models. This could be more cost-effective, easier to control, and more easily accessible.

Plant Feelings

To observe and measure the effects of anesthesia in the plants tested, researchers used three main tools: a single-lens reflex camera to capture plant organ movement throughout the anesthetic progression, confocal microscopy to analyze the movement of materials between cells, and a surface silver chrlodie electrode to record electrical signals. The results have been published in Annals of Botany.

Importantly, the anesthetics used in this study had no structural similarities, showing that the plants’ reactions were not coincidental or circumstantial. Rather, the study showed that anesthetics which work on humans and animals have the same effects in plants. The researchers themselves write that, because of this finding, “Plants emerge as ideal model objects to study general questions related to anaesthesia (sic), as well as to serve as a suitable test system for human anaesthesia.”

A researcher tests the effect of anesthetic on the plant Mimosa pudica, which normally closes its leaves when touched. (Video Credit: Yokawa et al)

This could make a huge difference in our understanding of anesthesia and testing methods going forward. While animal models have traditionally been seen as reliable and satisfactory for testing, there is a growing body of research which shows the glaring flaws in these experiments. Aside from any moral objections that some may have to the practice, animal models range from producing ineffective and inadequate data to being dangerously misleading. This is most obvious in looking at 20th-century smoking studies that, using animal models, misled the public about the true dangers of smoking cigarettes.

This new finding is at the very least fascinating and, at the most, a possible door opening to improved testing methods. Whether other plant-based testing will become possible is yet to be determined, but this study very concretely shows the parallel effects of anesthesia in animals, humans, and plants. It is even within the realm of possibility that because of these new testing models, improved anesthetics will be developed.

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