ALS Awareness Month Highlight MDA's Leadership in Research, Services

Once again, special attention is being focused on ALS during the month of May. To commemorate this year’s nationally designated ALS Awareness Month, MDA’s ALS Division has several new efforts under way to better serve those with the disorder and to raise the public’s awareness of the Association’s commitment to the fight to defeat it.

Since the early 1950s, when Eleanor Gehrig served as a national volunteer leader of MDA, the Association has led the effort to assist those affected by the disorder that takes its name from her husband, baseball great Lou Gehrig, who died of ALS in 1941.

"MDA will make a special effort in May to increase the nation’s knowledge about ALS and the people who have it, the progress being made in the search for a treatment or cure, and the vast amount of work that still needs to be done to defeat this devastating disease," MDA President & CEO Robert Ross said.

In 1956, Eleanor Gehrig assisted MDA President William Mazer at a groundbreaking ceremony for the Association’s Institute for Muscle Disease in New York. The widow of Lou Gehrig chose MDA as the organization to help her fight ALS.

MDA’s ALS Division offers the most comprehensive range of services of any voluntary health agency in the nation, and leads the search for a treatment or cure through its aggressive, worldwide research program. MDA has invested more than $135 million in its ALS program to date.

For a list of MDA’s 29 MDA/ALS centers, go to www.als-mda.org/clinics/alsserv.html. MDA materials produced to assist people with ALS and their families are listed below.

Among new ALS initiatives this year:

MDA’s ALS Division has a new logo for use on letterhead and other division materials. Lapel pins featuring the logo are available through local MDA offices.

Two prominent MDA publications on ALS are being revised, updated and reissued this month. "Facts About Amyotrophic Lateral Sclerosis" is an introductory MDA pamphlet geared to people who’ve just received an ALS diagnosis. "When a Loved One Has ALS: A Caregiver’s Guide" is a 60-page MDA book for family members and friends of people with ALS.

The MDA/ALS Newsletter this year is being published monthly, after six years as a bimonthly publication. (See February 2002.)

A new print public service ad, featuring Lou Gehrig and the slogan "A Champion Never Gives Up," is being distributed to newspapers and magazines.

An art exhibit called "Transcending Barriers to Creativity: Featuring Artists With ALS" will run from May 2 to May 10 at the Eleanor and Lou Gehrig MDA/ALS Center at New York’s Columbia Presbyterian Medical Center. The exhibit of works from the nationally recognized MDA Art Collection will tour other MDA/ALS centers in the Northeast later this year. (See April 2002.)

This month, MDA offices across the country will publish special newsletters, hold dedicated ALS fund-raising events, and conduct expert-led seminars and conferences on ALS.

Among the highlights: On May 28, designated MDA/ALS Awareness Day in Chicago, the Chicago White Sox will play the New York Yankees at Comiskey Park.

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Gene Therapy for ALS A Step Closer to Reality

by Margaret Wahl

Gyula Acsadi

MDA grantee Gyula Acsadi of the Departments of Pediatrics and Neurology at Wayne State University in Detroit was on a team that recently slowed disease progression in mice with ALS by using an innovative gene therapy technique.

The team presented some of the findings April 18 at the 54th annual meeting of the American Academy of Neurology, held in Denver, and will publish a paper in the June 10 issue of Human Gene Therapy.

In one set of experiments, Acsadi and colleagues inserted nerve-nourishing genes into adenoviruses and injected the gene-carrying viruses into the back and leg muscles of mice with ALS.

The researchers used a gene that codes for glial-derived neurotrophic factor (GDNF), a natural substance that nourishes and helps preserve nerve cells, including motor neurons, the muscle-controlling nerve cells affected in ALS.

Researchers inserted genes for GDNF into viruses, which they then injected into the muscles of ALS-affected mice. The GDNF genes probably traveled up the axons of nerve cells into the nerve cell bodies. The treatment appears to have slowed the course of ALS in these mice.

The treated mice began showing symptoms about a week later than their untreated counterparts and preserved motor function one to two weeks longer (as measured by their ability to hold onto a rotating rod). They also lived an average of 17 days longer.

Slowing disease progression by a similar degree in humans could add several years to the life of a person with ALS, the investigators say.

The scientists believe the GDNF probably extended the lives of motor neurons in the spinal cords of the mice.

Evidence suggests that GDNF genes probably traveled from the muscles to motor neurons, where GDNF protein was made. The protein was probably also produced in the injected muscle cells, the researchers say, and these protein molecules may have sent lifesaving signals back to the motor neurons.

In a second set of experiments, the researchers obtained similar results by using an adeno-associated virus to carry the GDNF genes. Adenoviruses have been known to cause dangerous immune responses that haven’t been seen with adeno-associated viruses.

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Bats and Nuts Yield Environmental Clue to ALS on Guam

High rates of ALS on Guam may have been caused by the native people’s predilection for eating bats, according to a new theory.

Two researchers proposed the theory based partly on observations that the bats — a delicacy among native Guamanians — eat poisonous nuts from the indigenous cycad tree.

"If we’re correct that an environmental toxin in the diet causes [ALS] among the people in Guam, it might lead to an investigation of environmental toxins — including dietary ones — elsewhere," said one of the researchers, Paul Alan Cox.

Cox is director of the National Tropical Botanical Garden in Kalaheo, Hawaii, which is chartered by Congress to conserve tropical plants and identify plant-derived medicines.

He and Oliver Sacks outlined the theory in the March 26 issue of Neurology. A best-selling author, Sacks is a neurologist at Albert Einstein College of Medicine in New York, and has examined ALS patients on Guam.

Between 1940 and 1965, ALS among native Guamanians — the Chamorro — reached 50 to 100 times its worldwide incidence, and became the Chamorro’s leading cause of death. In most cases, it was associated with Parkinson-dementia complex (PDC), a disorder that combines the tremor of Parkinson’s disease with the memory loss of Alzheimer’s. ALS-PDC wasn’t found among non-native Guamanians.

Today, pure ALS and ALS-PDC among the Chamorro have dropped to less conspicuous levels, suggesting that the trigger for the disease — something specific to the Chamorro lifestyle — has come and gone.

Cycad nuts, which are used by the Chamorro to make flour, were once a prime suspect. After studies showed that toxins from the nuts could cause neurological damage to animals, the use of cycad flour declined. But other studies revealed that the Chamorro had always known about the toxins and were efficient at removing them during flour preparation.

To most scientists, the cycad seemed off the hook. Research turned away from the Chamorro diet toward possible genetic risk factors.

But Cox kept digging. "Knowing that the only significant correlate with ALS-PDC in Guam was consumption of the Chamorro diet, I said ‘What else do these people eat that no one else in the world does?’" he recalled.

The answer: the fruit bat, boiled in coconut milk and then consumed from head to toe — a meal usually reserved for special occasions.

Since the bats feed on cycads and eat twice their body weight every night, their tissues could accumulate levels of toxin much higher than those in cycad flour, Cox said.

The theory also explains why ALS on Guam peaked after World War II, and then steadily declined, he said. The war brought money and guns to Guam, revving up the bat meat market. By the mid-1970s, steady hunting and consumption had nearly extinguished the bats, and Guam began importing bats from Samoa, where there are no indigenous cycad trees.

At its peak, ALS affected some 400 per 100,000 Chamorro, but now that the cycad-eating bats have disappeared, the rate is down to about 22 per 100,000.

Cox says the connection needs to be tested. Future studies should probe for cycad toxins in preserved and extant fruit bats from Guam, and investigate the eating habits of certain native tribes in New Guinea that have a high incidence of ALS, he said.

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Rilutek Safe but Weak; Better Drugs May Be on the Way

Scientists believe that toxic blasts of the brain chemical glutamate play a key role in ALS, so it’s come as some surprise — and great disappointment — that trials of glutamate-blocking drugs have shown little promise for treating the disease. But a recent study suggests that existing drugs may have been aimed at the wrong part of the glutamate pathway.

Glutamate acts as a messenger between neurons (nerve cells). When one neuron releases glutamate, another snatches it up using glutamate receptors. Attachment of glutamate to these receptors excites the neuron and causes it to "fire," but too much glutamate can push the neuron to the brink of death in a process known as excitotoxicity.

Riluzole (Rilutek), the only FDA-approved drug for treating ALS, works in part by blocking glutamate release. Unfortunately, it extends survival by only a few months.

In response to glutamate, synaptic NMDA receptors (white) promote neuron survival, while extrasynaptic NMDA receptors (black) trigger death. Drugs that target the extrasynaptic receptors might work against ALS.

Two other glutamate release blockers, gabapentin and lamotrigine, and dextromethorphan, which blocks the NMDA glutamate receptor, all failed to show any benefit against ALS in clinical trials.

The new study suggests that ALS researchers should be seeking drugs that block a subtype of NMDA receptor distinguished by its unique location on neurons.

Some NMDA receptors — the ones essential for neuronal communication — are clustered at a site where the neurons physically connect, called the synapse. Other receptors located away from the synapse, called extrasynaptic NMDA receptors, play a smaller role in neuronal communication, and according to the new study, a large role in excitotoxicity.

The study’s authors, led by Hilmar Bading of the University of Heidelberg in Germany, found that activation of synaptic NMDA receptors promotes the survival of neurons from a brain region called the hippocampus, but that activation of extrasynaptic NMDA receptors kills the neurons. In some diseases, they point out, the extrasynaptic receptors could be turned on by glutamate released from glial cells.

Their results, published online April 15 by Nature Neuroscience, offer hope that drugs targeting the extrasynaptic receptors might be effective for treating ALS and other neurological diseases that involve excitotoxicity.

Another study, published in September in ALS and Other Motor Neuron Disorders, confirms Rilutek’s good safety profile, but also points to its lack of potency.

In 1995, the developers of Rilutek (Aventis, formerly Rhone-Poulenc Rorer), began a study of nearly 8,000 people with ALS who were given free access to the drug before it became commercially available in the late 1990s.

Participants reported few problems attributable to Rilutek (taken at 100 milligrams per day), but many adverse events related to the progression of ALS. Mostly because of disease complications, 19 percent of participants died before the study’s completion, and another 9 percent had to withdraw.

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MDA's ALS Division Offers Unparalleled Services

The ALS services program provided by MDA is the most comprehensive offered by any volunteer health agency in the country. People affected by ALS and their families count on MDA’s ALS Division for clinical services, vital information and emotional support.

Those with ALS who are registered with MDA can receive diagnostic and follow-up examinations at MDA’s nationwide network of 230 hospital-affiliated clinics as well as 25 MDA/ALS clinical and research centers at major medical institutions across the country. MDA also offers support groups for those affected and their caregivers; assistance with purchase and repair of wheelchairs and leg braces; equipment loans; and information about participation in drug trials.

www.als-mda.org

MDA’s ALS Web site, www.als-mda.org, includes late-breaking news, MDA publications about ALS, back issues of The MDA/ALS Newsletter, and links to a list of ongoing and open clinical trials.

MDA’s online chat rooms (www.mda.org/chat/calendar.html) include several regular ALS chats, chats for caregivers, special seminars with ALS experts and more.

The following publications and videos are available at your local MDA office, from MDA National Headquarters at (800) 572-1717 or on the MDA/ALS Web site.

ALS: Maintaining Mobility: A 149-page book written specifically for people with ALS to assist in prolonging muscle function and enhancing independence. Prepared by the MDA/ALS Center medical team at Baylor College of Medicine. $6.

ALS: Maintaining Nutrition: A 130-page book geared to physicians covering swallowing, diet, alternative feeding methods and tube feeding. Prepared by the MDA/ALS Center medical team at Baylor College of Medicine. $6.

The MDA/ALS Newsletter: A monthly publication designed to provide news, with a focus on current ALS research, and profiles of people living with ALS. Mailed free to those registered with MDA who have ALS.

ALS Update: A 2-minute, 45-second review of ALS research progress as of summer 1998, hosted by MDA/ALS Center Director Stanley Appel. See at www.mda.org on RealPlayer (free download available).

Breath of Life and Breathe Easy: Two MDA videos about ventilation options for people with neuromuscular diseases. The first, at 25 minutes, is for medical professionals; the second, at 27 minutes, is for patients, families and caregivers.

Facts About Amyotrophic Lateral Sclerosis: An MDA pamphlet, revised in 2002, providing a detailed description of the disease’s symptoms, causes, treatments and current research. Free.

Los Hechos Sobre la Esclerosis Lateral Amiotrofica: The Spanish translation of Facts About ALS. Free.

Meals for Easy Swallowing: A 125-page book containing a collection of recipes for easy-to-swallow foods and beverages, as well as suggestions on food preparation and service. Prepared by the MDA/ALS Center medical team at Baylor College of Medicine. $6.

Quest: MDA’s bimonthly national newsmagazine, containing in-depth stories about issues of living with any of the neuromuscular diseases MDA covers, as well as Association activities, helpful products and research news. Mailed free to those registered with MDA; $14 yearly subscription for others.

When a Loved One Has ALS: A Caregiver’s Guide: A comprehensive, 60-page, illustrated manual filled with practical advice for meeting the medical, emotional, financial and everyday challenges faced by primary caregivers for people with ALS, and including an extensive list of resources. The primary caregiver for anyone with a diagnosis of ALS who is registered with MDA can receive a free copy of the guide, which was revised and updated in 2002. For others, there’s a charge of $10.

With Strength and Courage: Understanding and Living With ALS: A 24-minute video geared for newly identified ALS patients. Hosted by actor Ed Fry and featuring MDA/ALS Center Director Stanley H. Appel, the video was produced in 1996. It’s available for viewing from local MDA offices.

MDA/ALS Research and Clinical Centers

MDA’s ALS Division has designated 29 facilities at major medical institutions as ALS Research and Clinical Centers, indicating that they’re focal points of MDA’s ALS program. However, all of the 230 MDA clinics across the country serve people with ALS. For the names, directors and contact information for each MDA/ALS Research and Clinical Center, go to www.als-mda.org/clinics/alsserv.html.

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Attitude Is Everything, Harwood Says

by Chris Medvescek

"I can do it, I will do it."

That’s the approach Glenn Harwood chose when he was told he had ALS in 1994, and it continues to serve him well today, more than 10 years after he first experienced ALS symptoms. And it’s the approach he shares at every opportunity with people who have ALS, their caregivers and health care providers.

Glenn Harwood

Harwood’s upbeat, resilient attitude toward life represents the feelings of many people with ALS, which is why he was chosen to write the introduction to MDA’s newly revised and expanded booklet, "Facts About Amyotrophic Lateral Sclerosis."

The booklet is one of 15 introductory "Facts About…" MDA booklets about the individual neuromuscular diseases in the Association’s program. It’s available free at local MDA clinics or MDA offices.

Given "three to five years to live" eight years ago, Harwood, 62, of Crofton, Md., today leads "a full and rewarding life" with the help of modern technology and a loving family. A power wheelchair, voice synthesizer and e-mail enable him to continue working at the U.S. Small Business Administration, traveling and giving speeches to help educate others about life with his disease.

Harwood has "spoken" on local segments of the Jerry Lewis MDA Telethon, and was featured on the national broadcast in 1999.

He recently was asked to address second-year neurology students at Johns Hopkins University School of Medicine in Baltimore, and composed a speech describing his grueling year-and-a-half journey through medical tests before his ALS finally was diagnosed. Harwood hopes his speeches help doctors become more attuned to their patients as people.

"So you want to be neurologists, huh?" he electronically queried the doctors-in-training.

"You will need all your smarts and a lot of compassion and understanding of the human side of the diseases you treat. You, as future doctors, must be willing and able to assess a patient’s coping skills and map out a strategy for helping and dealing with them. …

"You doctors need to get out of your laboratories and offices and get to know the other side of your patients’ lives, the human side."

Harwood also informed the doctors that, "ALS is a community and family disease! My wife (Fran) carries the brunt of the load ... burnout and frustration are inevitable. I am knowledgeable of and thankful for all Fran does for me. Otherwise I would not be able to do what I do. I’m truly blessed."

Buoyed by his strong faith, Harwood believes part of his mission is to keep trying to bring a little laughter into the world. Renowned for his weekly e-mail joke dispatches, he says his motto is "Can’t Walk or Talk but Can Always Laugh."

"I prefer to be thankful for what I have, and go about being all that I can be," he told the Johns Hopkins students. "I’m frequently asked how I cope so well with a death sentence. The answer is in medicine, theology, philosophy and support mechanisms."

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Health Cluster Tracking Bill Introduced in Senate

What do San Antonio, Texas, the island of Guam and the Persian Gulf area have in common? They're all suspected of being ALS "hot spots," places where the disease is or was at one time more common than expected.

ALS clusters, as such disease groupings are called, could provide as many clues to the development of ALS as did a landmark finding in 1993 that a mutation in a gene on chromosome 21 is one cause of this disease. Many scientists believe most cases of ALS are due to combinations of genetic predisposition and exposure to as-yet-unidentified risk factors. Some of these may be lurking in the environment.

In March, U.S. Sens. Harry Reid of Nevada, Hillary Rodham Clinton of New York and Edward Kennedy of Massachusetts introduced a bill to create a national tracking database for clusters of chronic diseases like ALS.

If passed, S. 2054 would provide grants to the states to upgrade their health tracking systems; establish at least five regional laboratories to assist with the monitoring effort; and create a rapid-response service to help local officials deal with reports of chronic diseases that might be caused by environmental problems.

To contact your senator and express an opinion on the bill, go to www.senate.gov. Contact information for members of the House can be found at www.house.gov. Both sites have alphabetical and state-based listings.

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Letters

Dear MDA:

My husband was diagnosed with ALS and his doctor said you have two to three years to live. Then he said, "Take this medicine!" That's it ... no other help.

I was told to go to the MDA clinic by a family member. We came into a room filled with help. We were asked, What can we do for you?

If you haven't gone, go. It's free. We go to the clinic in Olympia, Wash. They can't all be as great as ours, but you can't go wrong checking out their support!

Cindy & Ted Stacy
Rochester, Wash.

To: Robert Ross
President & CEO
Muscular Dystrophy Association

Thank you for the generous support from the Muscular Dystrophy Association to benefit Jeffrey Rothstein's ALS research at Johns Hopkins Medicine. It is gratifying to know that our friends, graduates and those who have been treated here hold Hopkins in high regard.

I am always pleased to see, year after year, that the Hopkins Hospital and School of Medicine garner top rankings in surveys. However, it takes considerable resources to do things the "Hopkins way."

Your organization's philanthropy is a significant investment in our continued excellence, providing support for important initiatives in the Department of Neurology.

On behalf of those who will benefit from your support today and in the future, I thank you.

Best regards,
William R. Brody
President
Johns Hopkins University
Baltimore

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