Motor Neuron Neighbors Help Fight ALS

by Aaron Farnsworth

New findings indicate that neighboring cells can influence the health of motor neurons (nerve cells that control movement) either protectively or harmfully. This discovery could mean scientists will place more emphasis on strategies to correct or replace non-neuronal cells instead of treating or replacing the more complicated motor neurons in ALS.

In the most studied form of ALS — the type resulting from a mutated SOD1 gene — the actions of abnormal SOD1 molecules lead to a degeneration of the body’s motor neurons and to paralysis of all voluntary muscles.

Building on previous research, a study published in the Oct. 3 issue of Science says that other nerve cells, when they possess the normal SOD1 gene, lessen the severity of the disease caused by abnormal SOD1 in the motor neurons. These healthy neighboring cells prolonged survival in mice with a form of ALS.

While motor neurons constitute roughly 10 percent of nerve cells in the central nervous system, neighboring glial cells make up the majority. These cells were recently found to play a more important role in maintaining motor neuron health than previously believed, by offering both structural and functional support for motor neurons.

Robert Brown, who directs the MDA/ALS Center at the Massachusetts General Hospital in Boston, is among the study’s authors.

The study builds on work done by William Snider of the University of North Carolina Neuroscience Center in Chapel Hill and Jeffrey Elliott of the University of Texas Southwestern Medical Center in Dallas, both of whom have received MDA funding to explore the relationship between motor neurons and neighboring support cells.

In the recent experiments, the investigators studied mice with glial cells containing normal SOD1 genes but with the mutated form in their motor neurons. The mere presence of normal glial cells, even in the face of abnormal motor neurons, prolonged survival and delayed degeneration in the mice.

In contrast, mice with mutant SOD1 genes in their glial cells and normal motor neurons showed early signs of ALS, indicating to the investigators that motor neuron death was apparently provoked solely by damage to adjacent cells.

These interactions between the two cell types, still not well understood, suggest that treatments aimed at replacing abnormal glial cells with normal ones could bolster the strength of motor neurons in ALS.

1. In a healthy mouse or person, the motor neuron is surrounded by a framework of supportive glial cells. Both types of cells contain normal SOD1 protein molecules.

2. In a mouse model of ALS, motor neurons and glial cells have an abnormal form of the SOD1 protein, made from a mutated SOD1 gene. It is thought that downstream effects of this malformed protein are toxic to the central nervous system.

3. Glial cells with the normal SOD1 gene, even in the presence of motor neurons with mutant SOD1, prolonged the survival of the mice in these experiments.

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Wings Over Wall Street Posts Another Success

Co-host and singer Tony Orlando (rear center) shares a moment with the founders of the event, Toni Diamond (front center) and her husband Warren Schiffer, as well as Theresa Beier (rear left), widow of former Wings chairman Michael Beier.

More than 1,200 people attended the third annual Wings Over Wall Street gala for MDA Oct. 2, raising just over $1 million for ALS research in one evening.

Hosted by actor William Baldwin and co-hosted by singer Tony Orlando, the event at the New York Marriott Marquis in Times Square attracted a crowd of celebrities that included supermodel Bridget Hall, actor-comedian Garrett Morris and baseball great David Cone.

This year’s gala was held in honor of Michael P. Beier, a former director of equity trading at Credit Suisse First Boston and an MDA vice president. Beier, who had ALS, died this spring. His life was remembered in a video tribute accompanied by the song "Lullabye (Goodnight My Angel)" by Billy Joel.

Thomas M. Jessell, professor of biochemistry and molecular biophysics at Columbia University in New York, was presented the Diamond Award for his work with stem cells in the treatment of ALS. (The Diamond Award is named for Toni Diamond, who founded the Wings event with her husband Warren Schiffer in 2001 after her diagnosis of ALS. Diamond and Schiffer both attended the gala.)

Actor William Baldwin hosted the event for the second year. Photos courtesy of Jim Bulgatz Photography.

The Spirit Award was given to Eliot and Marjorie Danziger of Brookdale, N.Y., for their commitment to raising funds for MDA’s ALS program. Wall Street trader Cathy Wilson Rosen of Zweig-DiMenna Associates received the newly created Michael P. Beier Award for her extraordinary efforts in behalf of ALS research.

Live auction items included two guitars signed by the Rolling Stones, tour jackets signed by U2 and a dinner with Cone. In addition, a BMW roadster was raffled off.

In an impromptu moment, a woman in the audience offered Tony Orlando, an MDA national vice president, $5,000 to sing his hit song "Tie a Yellow Ribbon Round the Old Oak Tree." As he sang, other audience members threw money on the stage, raising several thousand more in a few minutes.

All of the funds raised at Wings Over Wall Street will be used to advance MDA’s ALS research program.

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A NEW LIFE WITH ALS

Denial — Don’t Deny Yourself Support

by Steven and Jennifer Bishop

Denial is a powerful weapon in fighting a devastating disease or situation, particularly when it allows one to enjoy the gift of life. However, it can also be unhealthy both mentally and physically.

We define psychological denial as a person’s lack of acknowledgement of a particular predicament. The result is that others who might like to understand and support the person in his or her struggle aren’t able to do so.

A friend of ours who’s dealing with several chronic medical conditions recently asked us how we stay so positive in the face of ALS. The ensuing conversation went in many directions for all parties involved and also fostered further self-discovery.

Several issues seem to get in the way of quality of life when denial determines your attitude. Three primary issues are: chronic pain, a feeling that you’re not meeting family responsibilities, and a lack of understanding from family, friends and others in your support network.

Chronic Pain

Chronic pain, resulting from medical or other conditions, can be overmedicated or undermedicated. Whatever the situation, it can lead to a feeling of constant desperation and change in personality. It’s difficult to be yourself when you hurt or have too many chemicals in your body.

You obviously should discuss alternative forms of pain management with your doctor, and ask your doctor to explain all of the treatment options.

Recently, we had a conversation with a newly diagnosed ALS patient and he was told the usual: two to five years survival, don’t do anything more than three months in advance and get your affairs in order. Oh yeah, the only thing that might help is Rilutek.

Not one thing was mentioned about symptomatic relief of cramps, spasms, twitches and joint pain, or anti-depressants for his reaction to the most devastating news most people will receive in their lives.

We don’t have control over what this disease does to our bodies. We do have control over how it affects us.

Don’t deny your pain — physical or emotional. Find professionals who can give you the help you need.

Family Responsibilities

Family responsibilities are very subjective. The fact that we might want to do more than we physically can is a message that must be made known to those we love.

Children, for example, may just think we aren’t interested in them, when in fact, we’re simply unable to interact as much as we’d like. This may happen especially if they don’t know the full ramifications of the
ALS situation.

When Steven began showing symptoms of ALS, our son had sympathetic aches and pains. He’d say, "My legs are too tired to walk, too," until he understood that Daddy has a disease that makes his muscles not work right, but that Christopher doesn’t have this problem. He surprised us with his understanding and compassion and continues to do so daily.

If Christopher asks whether ALS will kill Steven, we can honestly say, "We don’t know." None of us are guaranteed tomorrow and the way the end comes isn’t foretold to us. There also may be a cure or treatment right around the corner that none of us are aware of.

In marriage, we have an opportunity to reach an emotional level not tapped before. Of course, the physical challenges of taking care of a spouse with ALS shouldn’t be minimized. However, if we try to reach out and emotionally enhance the relationship, we may be able to offset some of the physical difficulties.

Again, we can only change things in our control. And the first step may be for husband and wife to stop denying the nature of the problem, so they can honestly reach solutions together.

Understanding & Support

Understanding and support from our circle of family and friends is in large part something we can control. If we live in denial, it’s difficult to let others know what we’re dealing with and therefore impossible for them to understand our situations.

We have the opportunity to let others into our lives. Some of the details of that life may be too much for some and relationships may change for the worse. On the other hand, if we let people know our challenges and open ourselves up emotionally, new relationships will form with old friends and new acquaintances.

We feel it’s imperative to have a sense of purpose. It can be simple or complex as long as it’s there every morning to bring forth another day.

When Steven stopped working and the doctors suggested we get our affairs in order, we did so. After that, a hole was left as to what we should do for the rest of our lives, however long that may be. We found our purpose mostly with our son and each other, but also with our volunteer work with the MDA.

Simply, the process of finding a new purpose is a life mission itself and worth the challenge of waking up every day.

Steven and Jennifer Bishop are co-chairpersons of the ALS Division of MDA. Steven received an ALS diagnosis in March 2001. The Bishops live in Arvada, Colo., with their 5-year-old son, Christopher. Join the Bishops every other Wednesday for the PALS With Children chat at www.mda.org.

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ALS Online

Several regular peer-led chats involving people with ALS or topics of interest to families affected by ALS are in MDA’s chat schedule.

PALS With Children is hosted by Steven and Jennifer Bishop, co-chairs of the ALS Division, and discusses the details of talking to your children of any age about living with ALS. The chat is held every other Wednesday from 9 to 10 p.m. Eastern time.

Living With ALS is for people with ALS and caregivers to share information about making life better. The chat is held every Monday from 4 to 6 p.m. Eastern.

The Spouse-Caregiver Chat is a support group for spouses and caregivers of people with any neuromuscular disease. The chat is held every Monday from 3:30 to 4:30 p.m. Eastern.

Positive Thinking is an upbeat and lively chat that’s all about maintaining a positive attitude with a disability. The chat is held every Thursday from 8 to 9 p.m. Eastern.

Watch www.mda.org/chat/calendar.html for announcements of upcoming chats about ALS.

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Monty Topche Paints a Picture of Creativity

by Kathy Wechsler

Monty and Mildred Topche are enjoying their retirement in Florida.

A resident of Lauderhill, Fla., Monty Topche, 78, adds a little color to his life through his magnificent watercolor paintings that have won him blue ribbons four years in a row at the Senior Citizens Art Show and Auction in Broward County. His artwork has been exhibited throughout Florida and has won a variety of awards.

Specializing in paintings of people, especially children, Topche finds that painting brings him much joy, while forcing him to concentrate fully on his task. For Topche, artwork is a great form of escape from his ALS and any other troubles. When he’s painting, nothing outside of his painting exists.

"I get such a charge out of seeing the finished product and finding acceptance by so many of our friends and other people who see my pictures," said Topche, who uses a walker to get around his condominium and a manual wheelchair for mobility away from home. "It’s a great feeling of accomplishment."

HOW IT ALL BEGAN

Topche donated this painting, "Out of the Bunker," as a prize in an MDA fund-raising golf tournament.

Born in London, Topche came to the United States after World War II, during which he served in the English army. He’s been painting for enjoyment ever since he retired in 1990 from selling textiles to women’s sportswear manufacturers in New York.

"I figured you need to have some outdoor activities so I learned to play golf and then I felt you needed something for indoors so I took up painting," Topche said.

As a child, Topche was very good at sketching. As he matured, the need to find a steady career and make a living diminished his chances of pursuing his interest in art. After retirement, he attended art classes and learned the basics of mixing colors, setting the stage for an old talent to blossom.

Topche received a diagnosis of ALS in 1999. As his outdoor activities decreased, painting became an important way to express himself and keep his time occupied.

But painting is more than just a hobby for Topche, who was asked to donate a painting for the University of Miami’s ALS Golf Classic, an annual MDA/ALS fund raiser. He submitted a painting of a golfer hitting a ball out of a sand trap, which was given as a prize to one of the tournament’s winners.

Mommy’s Little Helper" is an example of Topche’s fondness for painting pictures of children.

Topche recently designed a greeting card for the Jewish New Year (Rosh Hashanah, Sept. 27), featuring two rabbis, one holding a Torah and the other one blowing a shofar (ram’s horn). He donated the design to the Kessenich Family MDA/ALS Center at the University of Miami, which sold the cards to raise money for ALS research.

Not being able to stand for long periods of time, Topche now finds it difficult to participate in art shows. He still gets immense pleasure out of his paintings, and displays them in his condo.

THINK COLORFUL THOUGHTS

"Trying to keep my spirits up and trying to think positive makes me feel good," said Topche, who loves to paint clowns and other happy characters.

Topche finds that having a positive attitude is the only way to keep people coming around to visit; nobody wants to be around a depressed person, he adds. He enjoys listening to all kinds of music, making people laugh, socializing with friends and brightening their days with his artwork. His favorite thing to do is to paint while listening to music.

"I have a lot of people, neighbors and friends, who are very helpful and are always there for me if I need help. It’s a wonderful feeling," said Topche, whose wife, Mildred, always has an encouraging word. "That’s why I try to stay light with them, try and be funny, and act like a person who other people enjoy being with."

Topche has two grown children from a previous marriage. They live in New Jersey with their families and have made him a grandfather five times. Topche and Mildred both get to see their families once a year while visiting New York.

BRIGHTENING THE LIVES OF MANY

Attending MDA’s Kessenich Center for medical appointments every four months, Topche appreciates the efforts made by MDA.

"They send a van and a driver for me and take me to the clinic and bring me home," Topche said. "It’s quite a distance from where I live."

Topche borrowed a power wheelchair from MDA’s loan closet, which he uses when he takes the elevator downstairs and goes to the pool. Getting outdoors helps him remain active, healthy and happy.

ALS hasn’t affected his painting. Topche is thankful that his arms function well enough for him to paint without assistance.

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ALS Research Roundup

Minocycline Study Finally Opens

After some delays, a large-scale (phase 3) trial to test the safety and effectiveness of minocycline in ALS is now open at 24 centers.

Minocycline, an antibiotic in the tetracycline family (see "Evidence Mounts," June 2002), has been shown in animal studies to interfere with an important step in a cell death pathway thought to operate in ALS.

Two pilot studies in people with ALS showed the drug was, in general, well tolerated, but these small trials weren’t designed to test the drug’s effectiveness.

For information, contact Nayra Gad, project coordinator, at Columbia Presbyterian Medical Center in New York at (212) 305-3985 or ng152@ columbia.edu.

For details and up-to-date contact information for all study centers on these and other trials, please go to the clinical trials section of MDA’s Web site at www.mda.org/research/ctrials.aspx.

Mouse Studies Say Exercise, Hormone Levels May Influence ALS Course

A Dutch study has found that female mice with genetic ALS that were put on a treadmill exercise program showed their first ALS symptoms later and survived longer than their sedentary female counterparts with the disease.

Male mice with ALS didn’t show these same benefits, but the exercise didn’t do them any apparent harm.

The exercised mice ran on a treadmill for 45 minutes a day, five days a week.

The researchers say the exercise program probably led to higher estrogen levels in the females (though they weren’t able to measure these directly), and they speculate that estrogen may have had a protective effect on nerve cells. (This finding contrasts with reports that tamoxifen, which blocks estrogen’s actions, may also be beneficial in this disorder.)

The Dutch group also says the findings support a role for exercise in ALS, particularly in women.

The study, conducted by L.H. van den Berg and colleagues at University Medical Center in Utrecht, is in the November issue of Neuromuscular Disorders.

Pittsburgh & VA Probe Service Dog Use

The University of Pittsburgh and the Veterans Affairs Research & Development Center of Excellence for Wheelchairs and Related Technology are conducting a study of how service dogs affect wheelchair users’ lives.

People with and without service dogs may participate. If you don’t have a dog, you can be in a group that’s being compared to service dog owners.

The investigators are seeking people who are between 18 and 75 years old and use wheelchairs or scooters for at least 75 percent of their mobility. They’re asking participants to complete mailed or telephoned questionnaires, and they’ll pay $20 for each completed form.

For more information, contact Shirley Fitzgerald at (412) 365-4840 or Diane Collins at (412) 365-4844; or send e-mail to dmcst84@pitt.edu.

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STUDIES SHOW . . .

Part 2 in a series

CLUSTER OR CLUTTER?

by David Schoenfeld with Margaret Wahl

"Psychiatrists report massive numbers of people with anxiety following the attacks of Sept. 11."

"Toxic fumes may have led to cluster of 40 with ALS at Texas military base."

One kind of news that gets a lot of people’s attention is a location or activity that seems to be associated with something frightening. Known as a cluster, these are geographic or occupational concentrations of diseases, UFO sightings or other phenomena.

But not everything that looks like a meaningful cluster is one. Statisticians call the kind of attention that often puts clusters on the map an ascertainment bias, which means that the way the group was identified ("ascertained") in the first place biases the finding.

Are psychiatrists’ records the best way to estimate how widespread anxiety is in a particular population? Or are psychiatrists seeing ("ascertaining") what’s actually only a tiny percentage of the population?

And were the 40 ALS cases noted because someone who worked on the base and later developed ALS drew special attention to this workplace?

Although 40 cases of ALS among former employees of one military base sounds like a lot, it may not be. Important questions are: How many former employees were there in the group who didn’t get ALS? And, what’s the expected number of cases in this age group?

Even if more former base employees than expected developed ALS, this could still be a chance finding. This ex-employee group is actually one of many potential groups of former employees (for instance, ex-employees of other companies or institutions) that could have been examined but weren’t.

Chance alone can lead to finding that one ex-worker group has a higher rate of ALS than another ex-worker group, just as chance alone can lead to an excess (cluster) of "heads" or "tails" in one series of 10 coin tosses among many coin toss series.

If the investigators don’t have a specific factor in mind that goes with the cluster — a segregating factor — then it’s particularly hard to even begin to test the cluster’s meaning.

To find out whether service on the base really had anything to do with ALS development, there would have to be at least a hypothesis about a causative agent — for instance, a specific chemical toxin or high-altitude flight duty on the base.

Then you’d have to look around the country at retirees from other bases to see whether people who were similarly exposed to the proposed factor harbored a similar number of ALS cases.

Only then could you begin to separate clusters from clutter.

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HOSPICE: Comfort and Care

by Tara Wood

Hospice is a choice that many people with ALS make for their care during the final stages of the disease.

Quest, MDA’s bimonthly magazine, explores the topic of hospice service in the November-December issue. The article includes the varied hospice experiences of surviving family members of two people who had ALS, Judith Kay Hill of Edmond, Okla., and Randy Troyer of Spokane, Wash.

Here’s a brief summary of some of the concepts presented in the Quest article.

What is hospice?

The National Hospice and Palliative Care Organization defines hospice care as "a team-oriented approach to expert medical care, pain management, and emotional and spiritual support expressly tailored to the patient’s needs and wishes."

In addition, hospice care includes support for a patient’s loved ones. It’s centered around the idea "that each of us has the right to die pain-free and with dignity, and that our families will receive the necessary support to allow us to do so."

How can I find a hospice program in my community?

Hospice programs are listed in the phone book, but referrals from people with firsthand experience are often the most reliable sources. Good resources include MDA staff, support group members and others who are dealing with ALS. Also, the National Hospice and Palliative Care Organization (www.nhpco.org or [800] 658-8898) has a nationwide database of providers.

Are there different kinds of hospice programs?

In most cases, hospice care is provided in the patient’s home. Hospice care also is provided at hospice centers, hospitals, nursing homes and other long-term care facilities.

Hospice organizations may be nonprofit or for-profit. Nonprofit hospices usually take clients who have no means of paying for the services.

Are there specific concerns regarding hospice for someone with ALS?

Most hospices have extensive experience working with patients who have diseases like cancer, but many are unfamiliar with ALS. Before you select a hospice, be sure to ask if the staff has experience with ALS. If you face limited hospice choices, MDA staff can help familiarize staff with the unique concerns and needs of people with ALS.

Also, equipment is often an issue. Some MDA health care service coordinators said they often encourage patients to obtain any special or costly durable medical equipment before going on hospice care. Many hospices rely on equipment loan closets and can’t afford to supply higher-tech devices such as power wheelchairs, positioning systems or communication devices. Also, some insurance benefits — including Medicare — have specific hospice coverage that, for example, provides for manual wheelchairs but not power wheelchairs.

What about ventilators and feeding tubes?

Most hospices don’t accept patients who use ventilators because a vent is viewed as a life-prolonging form of treatment, but there are exceptions. The Hospice Patients Alliance advises that ventilator users might need to work closely with their physicians to obtain hospice care, and that ventilator use can also complicate the hospice "certification" process for insurance or Medicare coverage.

Feeding tubes are generally acceptable, however, as they’re seen as a means of providing comfort and sometimes the best way to administer medication.

What about cost and insurance coverage?

Hospice care is covered under Medicare, Medicaid in most states, most private insurance plans, HMOs and other managed care organizations. Families usually have very low out-of-pocket expenses, such as co-pays. If you have insurance, ask about hospice coverage.

Where to Go to Get a Break

Respite care is a service that provides temporary care to a person with a disability or serious illness in order to give caregivers and families a short break. Using respite care can enable family caregivers to better meet the daily demands of in-home care, but sometimes it’s hard to find this valuable service.

The National Respite Locator Service (NRLS), an online resource of the ARCH National Respite Network and Resource Center, helps caregivers find the respite service closest to them. NRLS also is useful when a family travels or moves to another state.

You can access the free locator service and a host of other good respite information at www.respitelocator.org. If you’re not online, call (800) 473-1727, extension 222.

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