Studies Strengthen Role of Glutamate, Abnormal RNA

by Margaret Wahl

Jeffrey Rothstein

Two recent studies strengthen the role of glutamate, a chemical that normally transmits signals between cells in the central nervous system, in causing or perpetuating ALS.

The first, which included MDA research grantee Jeffrey Rothstein at Johns Hopkins University Medical Center in Baltimore, where he directs the MDA/ALS Center, casts suspicion on a glutamate transporter, a protein that takes glutamate away from the area between nerve cells after it has transmitted a signal from one cell to another.

The second, a Japanese study, implicates excessive permeability in a glutamate receptor, a docking site on the surface of motor neurons that receives glutamate and transmits its signal to the cell’s interior.

The glutamate transporter study, published online Feb. 18 in Annals of Neurology, found that people with ALS make more of a glutamate transporter variant called EAAT2b and less of one called EAAT2, while people without ALS make mostly EAAT2 and very little EAAT2b.

The presence of EAAT2b instead of EAAT2 is thought to be due to a difference in the processing of RNA, the middle step in the transition from genes (DNA) to proteins (such as glutamate transporters) in cells. This difference may contribute to a toxic buildup of glutamate around nerve cells.

In the second study, Shin Kwak at the University of Tokyo and colleagues writing in the Feb. 26 issue of Nature, also implicate deficient RNA processing.

The Japanese group found that most of the motor neurons from ALS patients whom they studied had a defect in a late step in processing the RNA instructions for their glutamate receptors, while none of the motor neurons from those without ALS had this defect. This processing failure results in a structure that allows calcium into the motor neuron, a potential source of toxicity.

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Opening Our Hearts & Lives

by Reda Rice

Christopher and Reda Rice of Houston serve as co-chairpersons of MDA’s ALS Division. Chris, an information technology manager, received an ALS diagnosis in late 2001. The couple has three children, ages 4 through 6.

Chris and I are humbled to be representing the 35,000 U.S. families living with ALS as co-chairpersons of MDA’s ALS Division.

It’s an honor to represent these families. We’ve come to know many others facing ALS through our visits to the Ronny & Linda Finger MDA/ALS Center at Baylor College of Medicine in Houston, where Chris gets the best possible care. These families have become both a support system and a new sort of family for us. It’s hard to put into words how much we respect and admire them for their positive outlook on life.

We realize that we’re really no different from everyone else facing ALS, but I know that Chris is blessed with a slow progression of the disease. This allows us more time to be involved in helping MDA find lifesaving treatments.

Fighting for Time

Time is valuable to us all, so we’re serving in this honorary position to fight for time for everyone with ALS. We’re also fighting for added awareness, for more funding for MDA’s research and services programs, and, above all, for a cure.

We’ve been blessed to meet MDA employees and volunteers, at the local Telethon broadcast in Houston, at the national Telethon in Los Angeles last year, and during a recent visit to MDA’s national headquarters in Tucson, Ariz. These people make the organization what it is, and we’ve been nothing short of astounded at their kind and dedicated hearts.

During our visit to Tucson, we found an atmosphere of family unity and hope oozing from the walls. (Not to mention the most beautiful art in the world, painted by artists with various neuromuscular diseases!)

Many employees have been with MDA since the inception and we can understand why. It’s obvious that the mission to find cures is at the center of all they do.

It’s been said that an organization is only as good as the people running it. Well, with MDA National Chairman Jerry Lewis, President & CEO Bob Ross and Senior Vice President Jerry Weinberg at the top, we feel certain that MDA is as good as they come. Talk about three talented, smart and kind-hearted individuals!

Let the Blessings In

Chris and I share these things with you to give you faith and hope. If you haven’t already done so, allow MDA into your life and let the blessings flow!

Whether you’re facing ALS yourself, know someone who is or simply feel your heartstrings being tugged, there’s something for you at MDA. Allow this great organization to give you help and hope, just as it’s done for us, our family, our friends and even Chris’ co-workers.

We thank Jennifer and Steven Bishop for being such great role models as ALS Division co-chairpersons in 2003. They’re a truly courageous, loving couple who opened their lives to us all. We’re grateful for their honesty and their friendship.

Chris and I will try our best and help in any way we can. Know that all of you living with ALS are in our prayers, and you’re uppermost in our thoughts as we do our part to defeat ALS.

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Book Shows How to Extend the Joy of Dining

by Nancy Jones

The Dysphagia Cookbook: Great Tasting and Nutritious Recipes for People With Swallowing Difficulties, by Elayne Achilles, Ed.D., 161 pages, 2004, $14.95. Cumberland House Publishing, (615) 832-1171, www.cumberlandhouse.com.

In 2001, Elayne Achilles’ partner of 17 years received a diagnosis of ALS. Jackie Boswell’s muscle weakness first occurred in her throat, making speech, chewing and swallowing progressively difficult.

The two created new ways to continue enjoying fine dining. Now Achilles has compiled tips and recipes developed over the years into a beautifully written, comprehensive cookbook for those with dysphagia or chewing difficulties.

The foreword, by Todd D. Levine, is a general, illustrated explanation of the complexities of swallowing. Though the book was intended for people with ALS, Levine emphasizes that it can help anyone with dysphagia.

The varied recipes employ color, flavor, aroma and texture to help those with dysphagia enjoy dining. Achilles marks recipes with symbols to suggest levels of food consistency, and lists kitchen and pantry supplies to keep on hand.

Many of the recipes include serving options that meet various swallowing capabilities and enable all to enjoy the same menu. Because the rituals of eating and entertaining give definition and meaning to many lives, this cookbook provides the opportunity to restore joy and dignity to those whose pleasures have been limited.

Achilles lives in Phoenix. Boswell, a professor emeritus of music at Arizona State University, died in December.

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ALS Research Roundup

VEGF Deficiency Implicated in Second Disease

A recent MDA-supported study found that a deficiency of a protein called vascular endothelial growth factor (VEGF) is likely to be a major contributor to spinal-bulbar muscular atrophy (SBMA, or Kennedy’s disease), a motor neuron disorder that in some respects resembles ALS, though it’s less severe.

Albert La Spada

MDA grantees Albert La Spada at the University of Washington in Seattle and Lisa Ellerby of the Buck Institute in Novato, Calif., participated in the study.

Previous MDA-supported work by molecular geneticist Peter Carmeliet at Catholic University of Leuven in Belgium suggested that variations in the gene for VEGF are probably a risk factor for the development of ALS.

The root cause of SBMA is a genetic flaw in the gene for the androgen receptor, which transports androgens (male hormones) to the cell nucleus. But a study in the March 4 issue of Neuron shows that the downstream effect of the androgen receptor flaw is a deficiency of VEGF.

The new finding, coupled with the finding of VEGF genetic variations in ALS, raise the tantalizing question of whether giving VEGF to people with ALS or SBMA might help preserve their motor neurons — a question MDA research grantees will address.

Smoking Is Likely ALS Risk Factor

Smoking is probably a risk factor for developing ALS, experts say.

Carmel Armon, chief of the Division of Neurology at Baystate Medical Center in Springfield, Mass., told Neurology Today in February that accumulated evidence shows that smoking is "more likely than not" linked to ALS development.

Greg Carter, who co-directs the MDA/ALS Center at the University of Washington in Seattle, notes that such a link was first reported four years ago, and that the newer data appear to support the link.

The initial finding, published in the Jan. 15, 2000, issue of the American Journal of Epidemiology, was based on information gathered from people with and without ALS in Washington state between 1990 and 1994.

Epidemiologist Lorene Nelson, who left the University of Washington for Stanford (Calif.) University in 1992, worked on that study, as did UW neurologist W.T. Longstreth Jr., with Valerie McGuire and Chantal Matkin from Stanford’s Department of Health Research and Policy.

The UW-Stanford group reported that having ever smoked cigarettes was associated with twice the risk of developing ALS, while current smokers ran more than three times the risk of getting ALS compared to nonsmokers.

Biomarker Study Begins

Merit Cudkowicz, a neurologist at Massachusetts General Hospital in Boston who receives MDA support, is beginning a new study of biological markers in ALS that may aid in early diagnosis and be used to monitor the course of the disease during trials of new drugs.

Cudkowicz and colleagues are working closely with the Durham, N.C., biotechnology company Metabolon.

Novartis Study Full

The Novartis-sponsored study of TCH346, a compound that may help preserve motor neurons in ALS, has reached its recruitment target and is now closed.

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ALS Online

Clinical-Research Chats

Don’t miss the Respiration/Ventilation in Neuromuscular Disease Chat on May 19 from 5:30 p.m. to 6:30 p.m. (All chat times are Eastern.)

The chat will be led by Jerold Reynolds, a respiratory therapist on the faculty at Ohio State University in Columbus. Reynolds is a member of the clinic team at OSU’s MDA/ALS Center.

Meet MDA Medical and Science Editor Margaret Wahl on May 6 from 5:30 p.m. to 6:30 p.m., and learn how MDA reports news and other stories about research in neuromuscular diseases. The Medical/Science Reporting Chat will fill you in on how MDA follows medical and scientific news.

Several of MDA’s peer-led chats involving topics of interest to families affected by ALS will continue in 2004. They are:

• Living with ALS for people with ALS and their caregivers, every Monday, 4-6 p.m.
• Spouse-Caregiver Chat for spouses and caregivers of people with any neuromuscular disease, every Monday, 3:30-4:30 p.m.
• Positive Thinking, every Thursday, 8-9 p.m.

Watch www.mda.org/chat/calendar.html for announcements of new chats, including special expert-led chats on medical and research topics.

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Sidewalks and Happiness

by Frank Fois

Virginia Fois (seated) is aided by a loving family, including husband Frank (third from left, standing).

My wife, Virginia, was diagnosed with ALS in 1997. She’s now lost 80 percent to 90 percent of her mobility and uses a power wheelchair to move about.

As a family we continually adjust our lives to make life work for all of us.

I resigned from a corporate management position to become an independent manufacturer’s agent. This enables me to work out of my home and have more flexibility in the time that I need to take care of my wife. On occasion I have overnight travel for business so it’s fortunate that I also have plenty of help from other members of our family.

When our son, Michael, learned about his mother’s condition he moved back to Massachusetts from Jacksonville, Fla. He eventually began to work for me, which meant that he could help take care of his mom. Michael has become a pretty good cook as well as a sensitive and loving caregiver.

Our daughter, Ellen, dropped out of night school and changed her workday hours to an evening schedule. She drives an hour every morning before work to help her mom begin her daily routine.

To this day I can’t figure what’s going on with all the laughter and good time noise that takes place while Ellen is bathing and dressing her mom.

Friendly Town

Part of our routine, weather permitting, is to accompany Virginia for walks in her power chair with one of us tagging along trying to keep up with her. Wilbraham, a town in western Massachusetts (known locally as the home of Friendly’s ice cream), is where we call home.

Our neighborhood has safe residential side streets for Virginia to travel around, which she sometimes does alone when she escapes from our care.

We’re a mile from the center of town, and along the main road a paved walk heads to Main Street. There are five side streets that intersect the sidewalk. The walk has curbs that weren’t ramped at the intersecting streets so they were difficult for any wheeled vehicle to maneuver.

But Virginia wanted to travel to the center of town.

Last summer the town began paving the main road. On a whim, I called the town’s engineering department and asked about the possibility of installing ramps on the sidewalks for easier access while the street paving was in progress.

Donna Daviau, a polite and empathetic town hall secretary, said she’d look into it. She acknowledged that, like most every other town, Wilbraham was facing tight financial times and she didn’t know if anything could be done.

All the Way, Of Course

That same day Ed Miga and Tonya Basch from the town engineering office drove to our neighborhood to survey the situation. Coincidentally, they met my wife in her power chair a street over from our house.

They chatted for a while and then asked Virginia: If it were possible to do the ramps, how far up the road toward town would she like to have them put in?

She replied, "All the way, of course."

Miga smiled and said he’d look into it.

After about two weeks, they finished the paving, but nothing had been started with the walks.

Who’s Happy?

A while later, on my way home from a particularly uneventful business trip, I turned onto the road leading to our street. To my surprise there were town workers digging out the asphalt sidewalk curbs and pouring concrete ramps, all the way to the center of town.

Shortly after, I called the town office and thanked them for their fast and compassionate response. I went on to say that it was a beautiful sunny day when the yellow caution tape was removed from the walk. That’s when Virginia and I headed out to visit the local fruit farm on Main Street to have lunch and explore the center of town.

On the way back, we began to discuss our home, our family and friends, and how fortunate we were in so many aspects of our life.

It seems that many people don’t count their blessings and complain about personal disappointments or the way their lives have turned out.

I rhetorically asked, "Who claims to be really happy anyway?"

Virginia turned her head, looked at me straight on and replied, "I am."

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THANKS FOR LEG STORY

Dear Editor:

I have just read your article "Don't Let Leg Swelling Go Untreated" (February), and it was a revelation to me.

While I don’t have full-blown ALS I have a close relative — primary lateral sclerosis. My condition started in the legs and thus far has been largely confined to the legs, which have slowly become dysfunctional. I was diagnosed in 1994.

For several years now I’ve been having trouble with my right foot. Several doctors have attempted to treat it for infections, fungus, etc., but nothing seemed to make a permanent impact. I also have type 2 diabetes, which might be contributing its share to my problems.

After reading your essay I began to see the possibility of my PLS being a major contributor. None of the general practitioners knows the first thing about PLS.

Thank you for your helpful article on the subject of leg swelling.

Jim Parry
Lake Forest Park, Wash.

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Stay in Control by Making Advance Directives

by Christina Medvescek

Valerie Cwik

Uncomfortable though it may be, doctors strongly recommend knowing what treatments you would accept or reject in a medical emergency, and discussing your preferences with your loved ones and medical team.

Drafting a living will and appointing a health care agent by means of a medical power of attorney can help ensure that your wishes are followed if you become seriously ill and unable to communicate them yourself.

Most people with ALS stay conscious and able to communicate to the end, but this isn’t always the case, says MDA Medical Director Valerie Cwik. Thinking through the possibilities and leaving instructions is a way to stay in control of your medical care and your life.

"Talking about these things earlier rather than later is so important. These are not easy issues to discuss, and family members may be in denial and not want to hear it," says Cwik, a neurologist who was director of the MDA/ALS Center at the University of Arizona in Tucson.

"But the last thing we as medical professionals want to do is something that is against the patient’s wishes — either too much or too little."

The Tough Questions

A big question in ALS is whether to use mechanical ventilation when the diaphragm and other muscles required for breathing have weakened. Sometimes this decision is forced by a sudden respiratory crisis. When a patient doesn’t have enough breath to speak, it’s helpful if his or her wishes can be voiced by a significant other.

Other issues to consider are artificial nutrition and hydration, cardiopulmonary resuscitation (CPR), IV fluids and antibiotics. If a ventilator or feeding tube already is in place, under what circumstances might you want it removed?

Talk with your ALS doctor about emergency treatment options, as well as the types of emergencies that might arise at various stage in ALS.

"For example, in the early stages of ALS a patient having a heart attack might want to be resuscitated, but later on in the disease, no," Cwik says.

Equally as important as gathering medical information is taking stock of your values and beliefs. These subjects should be discussed with the people who’ll be helping with your care. (See "Making Your Wishes Known.")

Make It Legal

To ensure you get your way and to take the burden off caregivers, you can create advance directives — instructions about your care and designation of a decision maker.

As long as you’re making your own medical decisions, your advance directives are unused and you can accept or refuse any medical treatment, regardless of what you’ve indicated in the directives. But if you become unable to make decisions, the directives will provide a road map for others.

Two forms of advance directives are a living will (also called a directive to physicians or medical directive) and a medical power of attorney (sometimes called a durable power of attorney for health care or a health proxy).

Wills and Agents

Anyone who’s been in the hospital recently has been given a living will — a standard checkoff sheet listing treatment options you’d accept or reject. A living will can be this simple, or as specific as you want.

Usually, the immediate next of kin has the right to make medical decisions when a loved one is incapacitated. But there are reasons to legally designate a decision maker. For example, if your adult children might disagree or if you don’t have a competent next of kin, or if your decisions may change over time based on your health and circumstances, it’s useful to confer a medical power of attorney.

This means naming someone you trust (called a health care agent), who knows your wishes and is willing to make tough medical decisions. This person would make decisions when a doctor has certified in writing that you’re unable to do so.

You may cancel a medical power of attorney at any time, based on your state’s guidelines.

Do You Need Both?

Having a living will and designated decision maker(s) gives you structure and the flexibility to adapt to changing circumstances.

A living will provides the basic blueprint of your wishes, which your health care agent can flexibly apply to the specific situation. Is it early or late in the disease? What will be the quality of life after receiving the treatment in question? How do other recent events color the decision?

If the circumstances warrant, a trusted agent with medical power of attorney can override your living will decisions. By contrast, a next of kin without medical power of attorney must abide by your living will, although he or she could make decisions about things not covered by the will.

Do You Need a Lawyer?

An attorney isn’t necessary to execute advance directives. Forms are available at hospitals, doctors’ offices, or through state health, medical or bar associations. They’re also available online or in bookstores.

States usually honor out-of-state advance directives but if you regularly spend time elsewhere, fill out the forms for that location as well. Have documents notarized in the presence of two witnesses, neither of whom is named as health care agent.

See an attorney if you’re concerned that your directives might be challenged or if you’re worried about their legal effect.

Worth the Effort

The emergency room is no place to make life-or-death decisions or to guess what someone else would do. Although advance directives might never be used, there’s comfort and control in knowing you’re as prepared as possible.

"The decisions you make in a crisis situation are so different from the ones you make in a noncrisis setting," Cwik says. "We really encourage people to think and talk about these issues early on."

Chicago attorney Tim Halleron, who specializes in estates and trusts, provided guidance for this article. For information about setting up a nonmedical power of attorney, see "Plan Ahead for Disability," March.

Making Your Wishes Known

The following questions can help guide discussion. They’re from Partnership for Caring (www.partnershipforcaring.org; (800) 989-9455), which provides comprehensive information on advance directives and state-specific documents.

• How do you want to be treated at the end of your life?

• Are there treatments you want to receive or refuse?

• What are you afraid might happen if you couldn’t make decisions yourself?

• What are your attitudes about health, ALS, dying, independence and control?

• What are your moral or religious convictions?

• What do phrases like "no heroic measures" or "dying with dignity" mean to you?

Discuss your directives with your physician. Doctors aren’t required to follow directives if they disagree for moral or ethical reasons. In that case, another doctor will be called in to follow your directives.

Make photocopies for physicians, health care agent(s) and all caregivers. Keep the originals in a safe place that’s easily accessible to your health care agent (not a safe deposit box).

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Michael deKruif: Enjoying the Ride

by Kathy Wechsler

Michael and Donna deKruif at the Blessing of the Bikes at Crapo Park in Holly, Mich., last year. The annual event is led by a motorcycle ministry associated with deKruif’s church, called HIM (HOGs in Ministry).

There’s something about Michael deKruif of Waterford, Mich., that makes you want to be a better person. His difficult times only make him work harder to help improve the lives of people with terminal illnesses.

Since receiving a diagnosis of ALS in 2002, said deKruif, 51, his relationships with God, his family and friends have been strengthened.

Through Faith Baptist Church, deKruif got together with Shannon Veruink, a church member with multiple sclerosis, and developed Standing Strong, a support/Bible study group for people with terminal illnesses and their families and friends.

"The things that at one time you may have felt that they were important, you realize just how unimportant all that stuff is," deKruif said. "[ALS] makes you focus on what truly is important in life."

Changing Direction

In 2003, uncertain of how fast his disease would progress, deKruif had a "big pow-wow" with his family. They decided to close down their 7-year-old landscaping and excavating business, American Soil.

"One of the scariest things you can do is start a business," he said. "Then when it’s working, the next scariest thing is to shut it down."

Shortly after the last piece of landscaping equipment was sold, deKruif, who’d enjoyed riding motorcycles since he received his driver’s license and had owned a Harley-Davidson when he was 25, took a temporary job at ABC Harley-Davidson in Waterford. He worked as a prep and porter, washing, waxing and polishing the motorcycles and returning them to the service department after they’d been repaired.

"More than anything, the exercise was good for me and I met a lot of nice people and was involved in a couple of the fund-raising rides [for MDA]," deKruif said. He was losing some of his fine motor skills and his speech had become labored and slurred. He enjoyed his experience at the dealership until it ended in July.

Hog Heaven

A friend and coworker, Jim Hollingsworth, loaned deKruif and his wife of 25 years a Harley-Davidson Road King for a while last spring and summer.

"Donna and I felt like we were 15-year-old kids again," said deKruif, who refers to riding a motorcycle as "an exhilarating, uplifting experience."

The deKruifs visited the MDA summer camp in Lexington, Mich., an event that deKruif helped coordinate with Dick Rose of Motor City Harley-Davidson in Farmington. They brought in two motorcycles with sidecars to offer rides to the kids.

"We spent the whole day up there and had a wonderful time," deKruif recalled.

Wanting to give back to MDA for its guidance and support, deKruif has participated in five Lock-Ups and played the judge at the MDA fund-raiser. In February, the family participated in the MDA Family Walk in Auburn Hills, Mich. DeKruif is helping plan the second annual MDA/ALS fund-raising dinner, which will take place later this year in the Detroit area.

DeKruif is also speaking at an MDA fire fighter event this month.

During a profile for the local broadcast of the 2003 Jerry Lewis MDA Telethon, deKruif revealed his and Donna’s plans to buy a motor home and travel the country. The plan was put on hold when Donna was discovered to have breast cancer early this year.

"[MDA’s] like an extended family for my family and it’s been a blessing," said deKruif, who appreciates the fact that MDA staff members don’t treat him like "just a patient."

Finding What’s Important

Jessica, Donna, Michael and Justin deKruif at the first Michigan MDA/ALS Division fund-raising dinner at the Dearborn Inn in May 2003.

Last year, deKruif started taking a cocktail of prescribed medications along with some herbal supplements. With the advice of his neurologist, David A. Simpson, he also rides a stationary bike and works out with weight resistance machines to combat the effects of ALS.

His efforts are helping build muscle mass, he said. DeKruif is interested in sharing his successes with other ALS patients and can be reached at (248) 682-6478.

"I have actually not gotten much worse than I was a year ago," he said. "If it’s helping me, maybe it could help someone else, especially as devastating as I’ve seen this disease be to the families of people who get it."

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