Articles

GENETICS

After a Decades-Long Search, Scientists Identify New Genetic Risk Factors for Multiple Sclerosis

The National Institutes of Health (NIH)

Sunday, July 29, 2007

A pair of large-scale genetic studies supported by the National Institutes of Health has revealed two genes that influence the risk of getting multiple sclerosis (MS) – data sought since the discovery of the only other known MS susceptibility gene decades ago.  The findings could shed new light on what causes MS – a puzzling mix of genes, environment and immunity – and on potential treatments for at least 350,000 Americans who have the disease.

“These studies describe the first genes conclusively linked to MS in more than 20 years,” said Ursula Utz, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH. “This breakthrough was made possible through persistence, an elegant search strategy, and genomic data and techniques that were not available until recently.”

Both studies involved scanning DNA samples from more than 20,000 MS patients and unaffected individuals in the U.S. and Europe, and looking for single nucleotide polymorphisms (SNPs), which are single-letter variations in a gene’s DNA code.  Published simultaneously today in the New England Journal of Medicine* and Nature Genetics**, the studies demonstrate an association between MS and SNPs in two genes that encode interleukin receptors, proteins that serve as antennae on the surface of immune cells.

Both studies were supported by NINDS and the National Multiple Sclerosis Society.  The Nature Genetics study received additional support from the National Institute of General Medical Sciences (NIGMS).  The NEJM study was also supported by the National Institute of Allergy and Infectious Diseases (NIAID), the National Center for Research Resources (NCRR) and the Penates Foundation.

They were conducted by overlapping teams of scientists that used different gene-hunting strategies.  One team, which scanned the entire human genome for MS risk factors, was co-led by David Hafler, M.D., Professor of Neurology at Harvard Medical School and Brigham and Women’s Hospital in Boston, Stephen Hauser, M.D., Professor and Chair of Neurology at the University of California in San Francisco, and Alastair Compston, FRCP, Ph.D., Head of the Department of Clinical Neurosciences at the University of Cambridge, U.K.  The other team, which focused their search on a set of genes they considered potential risk factors for MS, was co-led by Jonathan Haines, Ph.D., Director of the Center for Human Genetics Research at Vanderbilt University Medical Center in Nashville, Tenn. and Margaret A. Pericak-Vance, Ph.D., Director of the Miami Institute for Human Genomics at the University of Miami.  Drs. Hauser, Compston, Haines and Pericak-Vance participated in both studies.

MS typically causes limb weakness, vision loss and problems with coordination, and is the most common disabling neurological disorder of young adults.  It’s an autoimmune disease, occurring when the body’s immune system mistakenly attacks a protective sheath around axons – the delicate cables that nerve cells use to connect with each other.  Various immunosuppressant drugs can reduce symptoms and slow the disease’s course, but most MS patients become increasingly disabled with time.

The trigger for MS is unclear, though there’s strong evidence for an interplay between genetic susceptibility and some type of environmental factor.  Having a relative, especially an identical twin, with MS increases one’s risk of developing the disease.  In the mid-1970s, researchers discovered that human leukocyte antigens (HLA) account for some of this genetic susceptibility.  HLAs are proteins displayed on all the body’s cells to help the immune system distinguish self from non-self.  A variant of the HLA-DRB1 gene, now widely accepted as the strongest genetic risk factor for MS, increases the likelihood of getting the disease up to four-fold.

Still, HLA does not fully explain the genetic basis of MS; scientists have long realized that other genes must play a role that has been difficult to detect.  Some studies have pointed to other HLA genes, but neither of the two genes reported today belong to that category.  Both genes encode receptors on the surface of T cells – the immune system’s mobile infantry – that enable the cells to respond to regulatory, secreted proteins called interleukins.

“These are the first non-HLA genes to be unequivocally associated with MS,” said Dr. Pericak-Vance.  “They give us a new way of looking at the biology of the disease, and could be targets for therapeutic development.”

Both studies searched for a link between MS and SNPs that were previously identified by the HapMap, an NIH-supported project to catalog genetic differences in human populations.

In the genome-wide association study, the first of its kind in MS, the researchers used gene chip technology to scan more than 500,000 SNPs.  In total, they analyzed more than 13,000 DNA samples, many of them collected and stored by the Center for Genetic Studies at the National Institute of Mental Health (NIMH) and the U.K.’s Wellcome Trust Case Control Consortium.  In the candidate gene study, the researchers scanned DNA samples from four large groups in the U.S, U.K. and Belgium, totaling more than 10,000 people.

Both studies revealed an association between MS and a single SNP in the gene interleukin 7 receptor-alpha (IL7R-alpha).  The genome-wide scan also found two SNPs in the gene for interleukin 2 receptor-alpha (IL2R-alpha) associated with the disease.  Both receptors are known to influence the way that T cells patrol the body for pathogens.  IL2R-alpha has previously been implicated in other autoimmune diseases, including type 1 diabetes.

Each of the SNPs associated with MS appears to increase the risk of developing the disease by about 20 to 30 percent.  Although that number might seem small, “it’s the size of effect we expect to see for genes outside of HLA,” said Dr. Haines.  Multiple genetic variations, each carrying a small risk of MS, could combine with one another and with environmental factors to create a large risk, he said.

The researchers who conducted the candidate gene search also think they know how variation in the IL7R-alpha gene affects the IL7R-alpha protein.  They found evidence that the MS-associated variant causes a reduction in the amount of the IL7R-alpha protein at the T cell surface.  Less is known about how variation in IL2R-alpha might contribute to MS, but that protein is already being viewed as useful therapeutic target.  In a 2004 study by NINDS scientists, 10 MS patients who were unresponsive to currently approved therapies showed improvement when treated with an antibody that blocks IL2R-alpha, developed to prevent rejection of organ transplants.

Finally, the genome-wide scan identified nearly a dozen other genes that could represent risk factors for MS.  Some of the associations were relatively weak and some of the genes’ functions are unclear.

“A major effort to understand the full complement of genes involved in MS will be necessary to completely understand the disease,” said Dr. Hafler, adding that all of the data from the genome scan will be made publicly available for future investigations.

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NINDS (www.ninds.nih.gov) is a component of the National Institutes of Health (NIH), and is the nation’s primary supporter of biomedical research on the brain and nervous system.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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*The International Multiple Sclerosis Genetics Consortium.  “Novel Risk Alleles for Multiple Sclerosis Identified by a Whole Genome Association Study.”  New England Journal of Medicine, published online July 29, 2007.

**Gregory SG et al.  “Allelic and Functional Association of the Interleukin 7 Receptor alpha Chain (IL7R-alpha) with Multiple Sclerosis.”  Nature Genetics, published online July 29, 2007.

© 2007 National Institutes of Health. All Rights Reserved.

PROFESSIONAL EVENTS, COURSES & WORKSHOPS

Scripps Center for Integrative Medicine

Bringing Integrative Medicine to Your Practice

October 27, 2007
January 17, 2008

Noon - 5 PM

This innovative symposium and site visit is designed for health care providers and administrators looking to create, introduce, or improve their integrative health care program.

From the role of philanthropy to strategic planning, the integrative medicine team at Scripps will share their real-world experiences and give you information you can use.

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Location: Paradise Point Resort, San Diego, CA.  A sunset cocktail reception overlooking San Diego Mission Bay follows the event.

For more information, or to register, call (858) 587-4404.

http://www.scripps.org/Services.asp?ID=299

© 2007 Scripps Health. All Rights Reserved.

FAMOUS QUOTATIONS

Our Deepest Fear is that We are Powerful

By Nelson Mandela

“Our deepest fear is not that we are inadequate. Our deepest fear is that we are powerful beyond measure. It is our light, not our darkness that most frightens us.

We ask ourselves, Who am I to be brilliant, gorgeous, talented, fabulous? Actually, who are you not to be? You are a child of God. Your playing small does not serve the world.

There is nothing enlightened about shrinking so that other people won’t feel insecure around you.

We are all meant to shine, as children do. We were born to make manifest the glory of God that is within us. It’s not just in some of us; it’s in everyone. And as we let our own light shine, we unconsciously give other people permission to do the same.

As we are liberated from our own fear, our presence automatically liberates others.”

© Nelson Mandela. All rights reserved.

ALTERNATIVE MEDICINE

Homeopathic Remedies Trigger the Body to Heal Itself

By Mark Isaac Thyss, Editor
Garden of Healing®

July 22, 2007

Homeopathic Medicine is both inexpensive and very effective.

Homeopathy is not a catch-all phrase for all alternative and complementary medical fields. It refers specifically to a branch of medicine founded by Samuel Hahnemann at the end of the eighteenth century.

Law of Similars
Homeopathic medicine is based on the Law of Similars, founded on the principle that likes will cure likes.

Rather than suppressing symptoms, for example, from food poisoning, homeopathy triggers the body into healing itself.

The average person might not be able to follow the logic behind this type of natural medicine. While the exact mechanism behind how it works is a matter of debate in some circles, homeopathy has successfully been treating patients for over 200 years.

Homeopathic remedies are created from thousands of natural substances, greatly diluted, and which in larger amounts would cause the same symptoms one is trying to cure.

Typical homeopathic remedies come in the form of little sugar pills that dissolve easily under the tongue or can be dissolved in small amounts of water, then given orally. The actual pills or pellets, come in small vials.

When shopping for homeopathic formulas, look for remedies that most closely describe your specific symptoms. For example, for food poisoning, look for:

Arsenicum album
Signs include diarrhea accompanied by anxiety. You may also feel restless or anxious and thirsty for cold drinks.

Urtica urens
This is the remedy of choice for shellfish poisoning, particularly if accompanied by hives that itch.

Veratrum album
This remedy may help severe vomiting (projectile vomiting) along with diarrhea, and/or if you are feeling faint from vomiting.

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Revolution in medical thought and practice
Homeopathy as a system of medicine has gone through several phases in its development.

Samuel Hahnemann rejected the allopathic attempt to find the cause of disease through dissection, chemical analysis, and endless theories. He ridiculed the allopathic battle cry, tolle causem (find the cause) and asserted that one could only know disease through the full individual symptoms of each sick person, the totality of symptoms. These were the language of the inner disturbance.

Classical and Constitutional
There are two major branches of homeopathy: Classical and Constitutional.

In the application of constitutional homeopathy, the selected remedy may not address the chief complaint but will fit the overall picture or constitution of the patient.

In constitutional homeopathy, the emphasis is placed upon the individual, including the underlying psychological issues, motives, personality and physical symptoms. Remedy selection is based upon the most distinct characteristics of the client matching the characteristics of the remedy which will enhance overall health.

Homeopathy is considered an effective natural method to repel imbalance out of the body and allow it to heal. The wonder of homeopathic medicine is in its safety, in the very small amount of medicine needed, and in the speed of healing.  It a great choice for addressing the ills of small children who embrace its use eagerly.

© 2007 Garden of Healing®. All rights reserved.

HEALTH & WELLNESS

Why Does Milk Cost More Than Gas?

By Nicholas von Hoffman, The Nation; Posted on July 16, 2007

Our unabated appetite for gas-guzzling cars and the wrongheaded belief that ethanol is the answer means pricey milk for everyone.

The other day milk was selling in a New England supermarket at $4.79 a gallon. Down the street, regular gasoline was going for about $3.04 a gallon.

One of the factors driving up the cost of milk is the ethanol stampede. Ethanol, as we all have been taught to believe by now, will bring us “energy independence” and lessen global warming with no change in the way we live — unless we happen to be a small child in a household with a limited budget.

Children from low-income families are either going to have to accustom themselves to drinking gasoline or learn to sing “No Milk Today.”

American ethanol is made from corn, and the more corn we use to feed our cars, the more expensive is the corn left over for our livestock. Ergo, “No Milk Today.”

If ethanol we must have, we could import it from Brazil, where they can make it cheaper from sugar cane than Americans can make it from corn. But Brazilian ethanol, thanks to the agribusiness lobby and a 54-cent-per-gallon import tariff, is kept out of the country.

Politicians of both parties, mad for winning elections in corn-growing Iowa, do not mention the cheaper Brazilian stuff. Their silence on lesser-cost alternative ethanol sources may help them please Midwestern agribusiness interests and just about nobody else.

But nobody else seems to know that, although it is not for lack of available information. The ethanol fraud has been exposed on mainstream TV on programs like ABC’s 20/20.

If ethanol is a failure as a practical short-term gasoline substitute, it is a political success. It will be years before ethanol has even a minor beneficial effect, which matters not to American politicians intent on slow-poking on climate warming, pollution and our ever-constricting energy sources. Kid the voters into thinking something is being done when it is not.

The energy bill gradually making its way through Congress contains a section upping the fuel-economy standards on gasoline-powered vehicles to take full effect when? In the year 2020. As of now cars in Europe and Japan get many more miles to the gallon than cars in America.

The last time the government imposed fuel-efficiency standards on cars was thirty-two years ago. In the intervening generation, car makers have learned to make more energy-efficient engines, but their technical progress has been defeated by making ever-larger automobiles. The Wall Street Journal reports that “models that started out as subcompacts have grown to become more like midsize models. Honda Motor Co.’s Civic CRX, a mid-1980s two-seater of 20 years ago, was 12 feet long and weighed about 1,700 pounds. Today’s Civic sedan is nearly three feet longer and weighs about 900 pounds more. Even the smaller Honda Fit, considered almost impossibly small today, is larger than the mid-1980s Civic CRX.”

The world is many years away from inventing and deploying oil substitutes. The present American policy of doing nothing until that day comes is short-sighted, idiotic and, ultimately, costly. Instead of making windy speeches about our “oil addiction,” our politicians should be at work making sure we use less of the stuff now.

Two measures of immediate effect could be put in place now. The first is to reduce speed limits on roads built with federal dollars. The second is a tax on the horsepower and weight of new cars. This should be an annual tax, not a one-time levy so that only the very rich will find that they can afford to drive overweight gas guzzlers.

Why should the rich get to guzzle gas when the rest of us cannot? Because, as someone once said, the rich are different. But we can also place a ruinous tax on their private airplanes. That ought to make the rest of us feel better even as, at long last, we take effective measures to deal with climate and energy.

Nicholas Von Hoffman is a columnist for the New York Observer and is the author, most recently, of “Hoax” (Nation Books, 2004).

Copyright © 2007 The Nation.  All rights reserved.

PERSONAL JOURNEY

Accept Yourself

Mark Isaac Thyss, Publisher, Garden of Healing®

I accept myself…  I am a good person.

I am doing the best I can.

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© 1997-2007 Garden of Healing®.  All rights reserved.