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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Botox, Brotox & Bladders

When someone mentions Botox injections, you probably think of Hollywood actresses with too perfect faces or wealthy housewives desperately trying to turn back time. Yes, we know it’s becoming more main stream, so maybe you’re also thinking about your own appointment for “shots” or maybe even “BroTox”. What we’re pretty sure you’re not thinking about is – incontinence. However, that’s exactly its newest use. Recently, the FDA approved using the injections to help patients with neurological conditions (such as multiple sclerosis or spinal cord injury) who suffer from either incontinence, or an overactive bladder. Neurologic conditions can cause miscommunication between the bladder and the brain.  As a result, the bladder muscle can become overactive, increasing the pressure in the bladder and decreasing the volume of urine the bladder can hold. This can lead to frequent, unexpected urine leakage, or urinary incontinence. Botox works by paralyzing bladder muscles, thus preventing the contractions that cause urgency or leakage. Although medications and behavioral modifications are treatment options, many patients, especially the elderly, do not respond to these methods and need a more aggressive approach. “About 80 percent of patients with neurological conditions, such as spinal cord injuries, Parkinson’s disease and multiple sclerosis, see improvement after about a week, and the results can last four to nine months,” says Charles Nager, MD, co-director of the UC San Diego Women’s Pelvic Medicine Center at UC San Diego Health System. Incontinence is the seventh condition, including chronic migraines, upper limb spasticity and underarm sweating, that Botox has been approved to treat since it first arrived on the market in 2002. The outpatient procedure uses a local numbing gel, followed by 15 -20 injections in different areas of the bladder muscle. “It can really be life changing for someone with severe incontinence issues,” said Nager. Want to share your Botox stories with SRxA’s Word on Health?  We’d love to hear from you.

Worming our way towards a Cure for M.S.?

Hot on the heels of our recent fecal transplant posting, SRxA’s Word on Health brings you news that might once again trigger your yuck factor.

According to an article in last week’s Wall Street Journal, help may be at hand, or maybe we should say “stomach” for people with multiple sclerosis – as the help is courtesy of  none other than parasitic worms.

Early safety studies conducted in the US suggest that the eggs of pig whipworms have anti-inflammatory properties that can reduce the size of brain lesions in MS patients. A similar trial is now under way in Denmark. And in Britain, academics at the University of Nottingham are studying the potential health benefits of hookworms.

If these trials prove successful, treatment with parasitic worms, or more correctly, helminthic therapy, could provide a simple, cheap, and controllable treatment for the debilitating condition, which affects 2.5 million people world-wide.

Multiple sclerosis is an inflammatory disease of the brain and spinal cord, in which an overactive immune system attacks the nerve fibers responsible for sending signals to the rest of the body. Its symptoms include impaired vision, muscle weakness and spasm, fatigue, memory loss and depression. Although a number of medications can slow the disease’s progression, many of them have unpleasant side effects including hair loss, muscle aches, sleeplessness and flu-like symptoms.

Interest in helminthic therapy surged in 2007 with the publication of an Argentina study which showed that the progression of multiple sclerosis was much slower in patients who carried parasitic worms in their intestines than in those who didn’t. Another recently published study in the Multiple Sclerosis Journal suggested that pig whipworm is effective in treating MS symptoms.

The results are quite promising,” says John Fleming, a professor of neurology at the University of Wisconsin School of Medicine and Public Health, who led the study.

Five patients took part in the Phase 1 trial. All were newly diagnosed with relapsing-remitting MS, a form of the disease in which new symptoms can appear and old ones resurface or worsen. Whipworm eggs were taken from disease-free pigs and grown in a clean laboratory environment. Every two weeks over the course of three months, the patients in the study drank 2,500 of the eggs mixed into a sports drink. The eggs hatched in the patient’s intestines and were killed by the immune system after about a week.  Patients who took part said the liquid was salty but didn’t taste or smell unpleasant.

During the study, patients underwent MRI scans, which tracked the number of new brain lesions that developed before, during and after they ingested the worm eggs.

What makes us optimistic is that brain lesions in four out of the five patients decreased over the course of the study and then rebounded after it finished,” says Dr. Fleming. While the pattern shown by the MRIs is encouraging, he adds, larger and longer studies will be needed before any definite conclusions are possible.

Researchers say the Wisconsin study’s findings could mean that the immune system’s over-response to the brain tissue was lessened by anti-inflammatory effects from the worms, and this could offer an alternative approach to treating MS.

The theory behind helmintic therapy is known as “the hygiene hypothesis.” This argues that developed countries such as the U.S., Europe and Japan have higher incidences of allergies and autoimmune diseases because the population has little or no exposure to parasites or infections. In developing countries, where people are exposed to low-level infections or infestations, the rates of such diseases are much lower.  Essentially, the proponents of this therapy argue, our immune system is created to be in balance with the worm’s influence on us.  Naturally, our body wants to fight the foreign nematode invaders, but the worms don’t like that and they’ve actually evolved to suppress our immune response to their presence.  That means that without them our immune system over-reacts to things that in its ancestral setting it would have ignored

We spoke to a friend of ours who has MS and asked, would you intentionally swallow worms if it would help control your disease? After some initial hesitation, she gave the idea the thumbs up.  “Although it sounds gross, it’s probably no worse than injecting myself every day with chemicals that I really know nothing about and which leave me looking like a pin cushion” she told us.

What about you?

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!