The Skinny on Breakthrough Myelin Sheath Disorders

MYELIN SHEATH DISORDERSIn patients with multiple sclerosis, cerebral palsy, and other rare genetic disorders known as leukodystrophies, the myelin sheath – the fatty covering that acts as an insulator around nerve fiber is progressively destroyed. Without this vital insulation, brain impulses to the rest of the body are lost leading to debilitating symptoms such as loss of muscle tone, movement, gait, speech, vision, hearing, ability to eat, and behavioral changes.

So we were very excited to learn that researchers at Case Western Reserve School of Medicine have discovered a technique that can directly convert skin cells to the type of brain cells destroyed in myelin disorders.

This amazing new technique involves converting fibroblasts – an abundant structural cell present in the skin and most organs – into oligodendrocytes, the type of cell responsible for myelinating the neurons of the brain.

Its ‘cellular alchemy,’” explains Paul Tesar, PhD, assistant professor of genetics and genome sciences at Case Western Reserve School of Medicine “We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy.”

axons-and-oligodendrocytesIn a process termed “cellular reprogramming,” researchers manipulated the levels of three naturally occurring proteins to induce fibroblast cells to become precursors to oligodendrocytes (called oligodendrocyte progenitor cells, or OPCs).  Tesar’s team, rapidly generated billions of these induced OPCs (iOPCs). They also showed that iOPCs could regenerate new myelin coatings around nerves after being transplanted to mice – a result that offers hope the technique might be used to treat human myelin disorders.

When oligodendrocytes are damaged or become dysfunctional in myelinating diseases, the insulating myelin coating that normally coats nerves is lost. A cure requires the myelin coating to be regenerated by replacement oligodendrocytes.  Until now, OPCs and oligodendrocytes could only be obtained from fetal tissue or pluripotent stem cells. These techniques have been valuable, but with limitations.

The myelin repair field has been hampered by an inability to rapidly generate safe and effective sources of functional oligodendrocytes,” explained co-author and myelin expert Robert Miller, PhD. “The new technique may overcome all of these issues by providing a rapid and streamlined way to directly generate functional myelin producing cells.”

BC7251-001This initial study used mouse cells. The critical next step is to demonstrate feasibility and safety using human cells in a lab setting. If successful, the technique could have widespread therapeutic application to human myelin disorders.

These are exciting times. The progression of stem cell biology is providing therapeutic opportunities that a decade ago would not have been thought possible. As always SRxA’s Word on Health, will bring you further developments on this story as soon as they’re released.

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The Skinny on Childhood MS

Childhood Obesity imageAs we’ve previously reported, childhood obesity is on the increase. Cases have more than doubled in children and tripled in adolescents in the past 30 years. The percentage of children and adolescents aged 6–18 years in the United States who are obese is now estimated to be >18%.

Childhood obesity can cause a number of health complications including diabeteshypertension, high cholesterolasthma  and emotional problems.  This is deeply troubling in and of itself, but now there’s a new cause for concern.

A new study has found that obese children and teenage girls may be more at risk for developing the chronic, debilitating central nervous system disorder – multiple sclerosis (MS).

Kaiser Permanente researchers studied 75 children aged 2 to 18 with pediatric MS, and compared them to more than 900,000 kids without the disease. Fifty percent of the kids with MS were overweight or obese, compared to 36% of the children who didn’t have the disease.

The study also found that the risk of developing multiple sclerosis was one-and-a-half times higher for overweight girls, almost two times higher for moderately obese girls and four times higher for extremely obese girls.

Mary Rensel, MD, who treats pediatric MS patients at Cleveland Clinic offers an explanation for the increased risk. “Fat increases the inflammation in the body. Multiple sclerosis is an auto-immune condition where the immune system is set too high. If there’s too much inflammation, it can increase the risk of having a disorder associated with inflammation – like MS.”

Childhood-Obesity-Linked-to-Multiple-SclerosisLead author, Annette Langer-Gould, MD, PhD, with the Kaiser Permanente Southern California Department of Research & Evaluation in Pasadena  “Even though pediatric MS remains rare, our study suggests that parents or caregivers of obese teenagers should pay attention to symptoms such as tingling and numbness or limb weakness, and bring them to a doctor’s attention,”

The researchers also stress that parents of overweight or obese children should play an active role in controlling their kids’ weight by getting them into the habits of eating healthy and getting enough exercise.

Dr. Rensel agrees, saying, “The good news is now we know. We can educate parents and patients of the importance of maintaining a healthy weight to decrease the chance of having consequences of being overweight.”

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Homeopathy gets a Nobel nod

Dr. Luc Montagnier, the French virologist who won the Nobel Prize in 2008 for discovering the AIDS virus, has surprised the scientific community with his strong support for homeopathic medicine.

In a remarkable interview published in Science magazine, Professor Montagnier expressed support for the often maligned and misunderstood medical specialty of homeopathic medicine. Although homeopathy has been around for >200 years, most conventional physicians and scientists have expressed skepticism about its efficacy due to the extremely small and highly diluted doses of medicines used.

Montagnier disagrees. “I can’t say that homeopathy is right in everything. What I can say now is that the high dilutions (used in homeopathy) are right. High dilutions of something are not nothing. They are water structures which mimic the original molecules.”

His experimental research confirms that even after sequential dilution, electromagnetic signals of the original medicine remains in the water and can have dramatic biological effects.

Montagnier has just taken a new position at Jiaotong University in Shanghai, China where his work will focus on the phenomenon of electromagnetic waves produced by DNA in water. He and his team will study both the theoretical basis and the possible applications in medicine.

He is confident  that these new observations will lead to novel treatments for many common chronic diseases, including but not limited to autism, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.

In the Science magazine interview Montagnier also expressed real concern about the unscientific atmosphere that presently exists on certain unconventional subjects such as homeopathy. When asked if he is concerned that he is drifting into pseudoscience, he replied adamantly: “No, because it’s not pseudoscience. It’s not quackery. These are real phenomena which deserve further study.”

This is in stark contrast to the recent statement from the British Medical Association who referred to homeopathy as “witchcraft.”

So, who’s right?  SRxA’s Word on Health wonders if it’s the case that when one goes on a witch hunt, one inevitably finds “witches!”

Let us know what you think.

Pac-Man Physiology

Yes, I admit it.  This Word on Health blogger has probably been spending way too much time recently think about blood cells. In the last week alone I have been re-learning basic anatomy and physiology as part of my paramedic course, providing training on infection control and cellular immunity to new emergency services recruits and preparing presentations on blood and coagulation disorders for one of our favorite clients.

So, it’s probably not altogether surprising that a news story about the expanded role of macrophages caught my eye.

For most of our readers, I suspect that the term “macrophage” conjures images of a hungry white blood cell gobbling invading bacteria, in a manner reminiscent of  the 1980’s iconic Pac-man.

It emerges however, that macrophages do much more than that.  Not only do they act as antimicrobial warriors, they also play critical roles in immune regulation and wound-healing.   Additionally, they can respond to a variety of cellular signals and change their physiology in response to local cues.

There has been a huge outpouring of research about host defense that has overshadowed the many diverse activities that these cells do all the time,” said Dr. David Mosser, Professor of Cell Biology and Molecular Genetics at the University of Maryland.  “We’d like to dispel the narrow notion most people have that macrophages’ only role is defense, and expand it to include their role in homeostasis.”

So what are macrophages?  Well, they exist in nearly all tissues and are produced when specialized white blood cells called monocytes leave the blood and differentiate in a tissue-specific manner. The type of macrophage that results from monocyte differentiation depends on the type(s) of cytokines that these cells encounter on their journey. Cytokines, for those not in the know, are proteins produced by immune cells that can influence cell behavior and affect interactions between cells.

For example, macrophages that battle microbial invaders appear in response to interferon-γ, a cytokine that is produced during a cellular immune response involving helper T-cells and the factors they produce. These macrophages are considered to be “classically activated.”

However, when monocytes differentiate in response to stimuli such as prostaglandins or glucocorticoids, the resulting macrophages will assume a “regulatory” phenotype.

Alternately, wound-healing macrophages arise when monocytes differentiate in response to interleukin-4, a cytokine which is released during tissue injury.

According to Dr. Mosser, macrophages can change their physiology and switch types. For example, in healthy, non-obese people, macrophages in fat tend to function as wound-healing macrophages. They are also thought to maintain insulin sensitivity in adipose cells. However, should an individual become obese, macrophages in fat will instead promote inflammation and cause the adipose cells to become resistant to insulin.  Similarly, immune-regulating macrophages produce high levels of the cytokine interleukin-10, which helps suppress the body’s immune response. Suppressing an immune response may seem counter-intuitive, but in the later stages of immunity it comes in handy because it limits inflammation.

According to Mosser, immune-regulating macrophages may hold the key to developing treatments for autoimmune diseases such as multiple sclerosis or rheumatoid arthritis. The focus of new research is on reprogramming the macrophages to assume a regulatory phenotype and prevent autoimmunity.

It might be possible to manipulate macrophages to make better vaccines, prevent immunosuppression, or develop novel therapeutics that promote anti-inflammatory immune responses.”

All of which kind of leads me back to the Pac-man analogy. In the video arcade game, when all the initial dots are eaten, Pac-Man is taken to the next stage where he gets to take on other enemies.   Here, despite the seemingly random nature of the enemies movements, they are in fact strictly deterministic.  Exactly, the same it seems, as it is with macrophages.

Suddenly learning Anatomy and Physiology may get a whole load more interesting for those back-to-school teens!

Milk can cut kids’ MS risk by 56%

Word on Health has just learned of a study that suggests drinking milk during pregnancy may help reduce a baby’s chances of developing multiple sclerosis (MS).  Researchers from Harvard School of Public Health will present preliminary results at the upcoming meeting of the American Academy of Neurology.

The data we’ve seen so far look very interesting. More than 35,000 mothers were surveyed over a 16 year period. The risk of their daughters developing MS was 56% lower for mothers who drank four or more glasses of milk a day, compared to those that drank 3 or less glasses / month.

The results add further credibility to earlier studies that link MS with vitamin D deficiency.

While these findings are not going to change the lives of the 350,000 Americans currently estimated to have MS, they may, in the future, be able to prevent some of the 200 new cases diagnosed each week.

More importantly this study may be able to reduce the 2.5 billion dollars the US spends each year on MS care.

Got Milk?  Word on Health is stocking up!