Anti-Arthritic to Be Tested Against ALS

Daniel B. Drachman

Thanks to a growing numberof supportive studies, the arthritis drug Celebrex may soon be tested in clinical trials for ALS.

The drug, which blocks the activity of a protein called COX-2, has shown promise in laboratory models of ALS. And now, "We've put together a consortium and we're planning on doing a large multicenter trial to test the drug [in people with ALS]," says MDA grantee Daniel B. Drachman of John Hopkins University in Baltimore.

Given the encouraging laboratory results, Drachman and others anticipate beneficial effects in people — even though they're still not exactly sure how COX-2 is involved in ALS. "I would certainly not say that COX-2 is the cause of ALS, but I think that in many cases — maybe all — it plays a role in the disease," says Drachman.

A Multifaceted Approach

In fact, researchers have several different theories about the disease process in ALS, and COX-2 fits neatly into some of the most prominent ones. While researchers know that the paralyzing and eventually fatal course of ALS is caused by the death of muscle-controlling nerve cells (motor neurons) in the spinal cord and brain, they can't yet explain why the cells die.

One theory of ALS holds that the motor neurons are damaged by inflammation, a response normally directed against injured or infected tissue. Another suggests that the buildup of destructive molecules called free radicals contributes to motor neuron death. And the excitotoxicity theory says the motor neurons are damaged by an overexposure to glutamate, the excitatory chemical signal that tells motor neurons to "fire."

All three disease processes might actually contribute to ALS, and COX-2 could play a role in each one, Drachman says. That makes treatment with COX-2 inhibitors like Celebrex "a multifaceted approach," Drachman says.

COX-2 and its close relative COX-1 are both versions of the cyclooxygenase protein. A major function of both COX proteins is to manufacture prostaglandins, locally acting hormones that promote inflammation. Free radicals, it turns out, are a byproduct of that manufacturing process. What's more, a recent study found that prostaglandins can stimulate the release of glutamate from astrocytes, cells in the brain and spinal cord that normally collect and store excess glutamate.

The protein COX-2 may be involved in ALS in one of three ways

Taking Aim at COX-2

Supporting Drachman's theory about a COX-2 connection, in an MDA-funded study, Serge Przedborski and his team at Columbia University in New York found increased levels of COX-2 in the spinal cords of mice carrying disease-causing SOD1 mutations. Przedborski and his team also observed increased levels of the COX product prostaglandin E2 in spinal cords from the mice and from people who died of sporadic ALS. That study appeared in the February issue of Annals of Neurology.

Putting Celebrex to the Test

To find out if COX-2 inhibitors would make effective weapons against ALS, Drachman combined forces with Jeffrey D. Rothstein. (Drachman and Rothstein are co-directors of the MDA/ALS Center at Johns Hopkins.)

With MDA backing, Rothstein and Drachman first tested a close Celebrex relative in rat motor neurons exposed to excitotoxic levels of glutamate. In the November 2000 issue of Annals of Neurology, they reported that the drug significantly protected the rat motor neurons from excitotoxic death.

Since then, Drachman and Rothstein have found preliminary evidence that Celebrex significantly prolongs the survival of mutant SOD1 mice. (In contrast, a 1999 study by French re-searchers found that aspirin had no effect on survival of the mice.)

To set up clinical trials to determine whether selective COX-2 inhibitors are beneficial to people with ALS, Drach-man is collaborating with Rothstein, MDA grantee Merit Cudkowicz of Massachusetts General Hospital in Boston and Jeremy Shefner of SUNY Upstate Medical University in Syracuse, N.Y.

"We're hopeful that COX-2 inhibitors will interrupt the cascade of damage that occurs [in ALS]," he says. "But we really need to test them scientifically in a controlled way. We don't want people to rush out and take COX-2 inhibitors or other NSAIDs, and come back with [gastrointestinal] bleeding or other problems." He's hopeful that a clinical trial of Celebrex will begin by this summer.  

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NONINVASIVE VENTILATION CAN'T SUSTAIN LIFE INDEFINITELY IN ALS

MDA/ALS Center Director Recommends Better Planning

Using a noninvasive ventilation device in ALS may actually weaken respiratory muscles faster than not using one, a preliminary study in the March issue of Muscle & Nerve suggests. On the other hand, the use of such devices was found by the researchers to relieve fatigue, to promote a sense of mastery over the illness, and even to prolong survival.

Noninvasive ventilation is a term for air delivered through natural openings in the body, such as the nose or mouth, while invasive ventilation means air delivered through a surgical hole in the neck directly into the trachea (windpipe) through a tracheostomy tube. As ALS weakens respiratory muscles, those affected often need a form of assisted ventilation.

A BiPAP machine is a form of noninvasive ventilation that can be used part-time.

A common noninvasive ventilation device is the BiPAP, which stands for "bi-level positive airway pressure." One air pressure is delivered for inhalation, another for expiration. (The name is actually a registered trademark of the Respironics Company of Pittsburgh but is widely used in a generic sense.) BiPAP machines are generally portable and convenient compared with the type of machine usually used to deliver air with a tracheostomy tube. (For more on ventilation, see "What Everyone With ALS Should Know About Breathing," ALS Newsletter, vol. 5, no. 4, 2000; and two articles on breathing and ventilation in Quest, vol. 5, nos. 5 and 6, 1998.)

COULD BiPAP BE HARMFUL?

At least two recent journal publications — a letter in the Feb. 15 New England Journal of Medicine as well as the Muscle & Nerve article — have raised questions about whether noninvasive ventilation is helpful for people with ALS, whether it's dangerous to rely on it instead of moving to tracheostomy ventilation, and what effect noninvasive ventilation has on respiratory function.

The New England Journal letter recountsthe story of a man with ALS who died after a mechanical failure turned off his BiPAP system.

The Muscle & Nerve article reports a small study that found that measures of pulmonary (lung) function deteriorated in people with ALS who were using noninvasive ventilation while also finding that people felt better and lived longer when they were using it.

People who were able to sleep while using a noninvasive ventilation device lived an average of 20 months from the time of the study's beginning, while those who couldn't sleep with it on lived an average of five months. The study found that measures of pulmonary muscle function and blood oxygen and carbon dioxide levels, taken when the person was off the assistive device, declined over time despite the use of noninvasive ventilation for varying periods during the night and day.

Hiroshi Mitsumoto

IMPROVED QUALITY OF LIFE

Hiroshi Mitsumoto, a neurologist and neuromuscular disease specialist who directs the Eleanor and Lou Gehrig MDA/ALS Center at Columbia Presbyterian Medical Center in New York, was part of the Muscle &Nerve study.

"It sounds contradictory," Mitsumoto said of the study. Noninvasive ventilation, he says, "may make pulmonary function worse, but the patient lives longer and his quality of life is better. So the question is, 'Is it good to have BiPAP or other noninvasive ventilation, or bad to have it?'"

Mitsumoto says the situation can be compared to that of someone with weak leg muscles who wears a brace. The leg muscles may weaken faster through disuse than they would if the person were trying to use them, but his function — walking — actually improves, because the leg is supported by the brace.

"I think the [noninvasive] ventilator is doing the same thing," he says. "It's providing better ventilation but deconditioning the muscles at the same time." Mitsumoto noted that more studies need to be done to verify the results of these limited observations.

BiPAP WON'T WORK INDEFINITELY

The important thing for people with ALS and their caregivers to keep in mind, Mitsumoto said, is that BiPAP or other noninvasive ventilation won't be effective indefinitely in ALS. There will come a time when respiratory failure, even with a noninvasive vent system, forces the patient or caregiver to make an emergency choice — whether or not a tracheostomy should be performed and invasive ventilation started. This kind of ventilation can achieve more control and offer better assistance to failing respiratory muscles.

When to begin thinking about moving to invasive ventilation can be a "tough question," Mitsumoto says.

"Increasing dependency on BiPAP during the night and even during the day is clearly one sign," he notes. "Increasing discomfort, despite using the BiPAP, is clearly another. Patients must be followed closely by a pulmonary doctor who has extensive experience with ALS. There's no simple, cookbook answer here."

Other experts have noted that morning headaches, increasing sleepiness, a sense of mental fuzziness, and increasing anxiety, particularly when lying down, are also signs that a person may not be getting adequate ventilatory support. Shortness of breath may or may not be perceived.

After a tracheostomy, air is delivered directly to the windpipe.

PLANNING AHEAD

It's best, Mitsumoto said, to have one's thoughts in writing in an advance directive before an emergency, such as a respiratory crisis or equipment failure, arises.

It's also important, he noted, to keep emergency resuscitation bags (often called Ambu bags) close by and to make sure someone can give temporary ventilation, if that's needed, while waiting for professional assistance.

Many people with ALS, Mitsumoto said, avoid discussing end-of-life issues with their doctors and families.

"How they want to deal with their life is not fully discussed," he said, "but they keep using [noninvasive] BiPAP. Meanwhile, their condition deteriorates, and serious problems can occur."

BiPAP and other noninvasive ventilation systems, he said, are "not an answer" for long-term survival.

"If they want to live [for a long time], they have to tell the doctor, and a prophylactic trach should be done," Mitsumoto said.

"There is a lot of misunderstanding and miscommunication. BiPAP is not a machine to be used for long-term survival. Its primary effect is symptomatic relief. More and more people have started depending on BiPAP to live longer, but that's really the wrong usage. The BiPAP machine was not developed for that purpose.

"When they use BiPAP, they should have a good idea of what they want to do. Advance directives should be discussed early. When a BiPAP is utilized without discussing those issues, it's problematic."  

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MARK KESSENICH, BUSINESSMAN AND BENEFACTOR, DIES

Mark F. Kessenich

Mark F. Kessenich Jr., an MDA national vice president and the founder of the Kessenich Family MDA/ALS Center at the University of Miami, passed away on March 20.

Kessenich died from the effects of ALS, a disease he was found to have in 1994. He was 62.

Despite the progressive effects of ALS, Kessenich remained an active and successful businessman for several years. He was best known in Wall Street circles for his successful bond trading operations, which thrived in the 1980s and 1990s.

Kessenich, who had residences in Westhampton, N.Y., and Palm Beach, Fla., applied the same tenacity that made him a bond market legend to the fight against ALS.

Having received treatment at the Eleanor and Lou Gehrig MDA/ALS Center at Columbia Presbyterian Medical Center in New York, he wanted to ensure that a similar center for people with ALS would be available in Florida. So Kessenich and his family dedicated themselves to fund-raising initiatives and the establishment of the Kessenich Family MDA/ ALS Center Term Endowment Fund to create a center that would provide the highest level of ALS care.

The $3 million fund began with a $1.75 million donation to MDA from the Kessenich Family Charitable Trust, and made possible the opening of the Miami center on March 4, 1998.

The center, which operates through the Department of Neurology at the university's School of Medicine, conducts ALS research and provides a full range of services from medical care to physical therapy to social support for ALS patients and their families.

"Mark Kessenich was an unselfish crusader who'll be fondly remembered for his remarkable courage and generosity. We're deeply saddened by his passing," MDA Senior Vice President and Executive Director Robert Ross said. "MDA will continue to strive for the goals he shared of improving the quality of life of people with ALS and, of course, of ultimately wiping out the disease altogether."

Kessenich is survived by three children, a sister and eight grandchildren. His wife, Beverly, died in 2000.

More information about the Kessenich Family Center can be found at www.miami-als.org.  

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Atlanta Man Inspires New Medicare Homebound Law

David Jayne, 40, of Rex, Ga., is a long-term survivor well known in the ALS community as a mentor and a champion of issues concerning people with ALS.

Recently Jayne has been the driving force behind reintroduction of the Homebound Clarification Act of 2001, H.R. 1490. The federal measure aims to expand on a recent loosening of the definition of "homebound" for people who receive in-home assistance provided through Medicare.

Medicare traditionally has provided in-home care for Social Security Disability Insurance recipients who are "homebound," meaning they could leave home only for visits that are "brief, infrequent and medically necessary."

The definition was expanded in December 2000 to allow people considered homebound to attend adult-day care programs and religious services. Jayne would like to see the definition made even less restrictive.

After failing last year to gain support, the House bill was reintroduced this spring by Rep. Edward J. Markey, D-Mass., and is endorsed by some 30 organizations, including MDA's National Task Force on Public Awareness. It proposes a new standard: that leaving home should usually require "considerable or taxing effort."

Such is the case for Jayne, a former stockbroker and outdoorsman who now uses a ventilator because of ALS.

Since 1997 help for his two-hour morning routine has come from a personal care attendant whose services are covered by Medicare.

Occasionally Jayne leaves home to give speeches or attend his children's activities. He knows such outings could jeopardize his assistance under current Medicare regulations.

"I was always at risk of being discharged and that was a terrible feeling. I felt I was being deceitful just trying to be a part of my family," Jayne said.

Last year he challenged his home health company and Medicare by discussing his occasional outings in an Atlanta Journal-Constitution profile, including a rare overnight trip to his college's football game.

Shortly after, his in-home assistance, provided by Healthfield Home Health, was suspended. After he contacted both his congressman, Michael "Mac" Collins, and Healthfield CEO Tony Strange, Jayne's in-home care was reinstated.

As a result of the experience, Jayne formed the National Coalition to Amend the Medical Homebound Restriction for Americans with Significant Chronic Illness (NCAHB). He also authored a petition circulated by Internet that has garnered 15,000 signatures. For more details, visit www.amendhomeboundpolicy.homestead.com.  

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MDA BOOSTS ALS PROGRAM DURING AWARENESS MONTH

For the 10th consecutive year, May will be "National ALS Awareness Month," reflecting a national recognition of the fight against the disease that MDA has led for some five decades. MDA was instrumental in supporting the first ALS Awareness Month, declared by the U.S. Senate in 1992.

In keeping with the annual observance, the ALS Division of MDA has announced several additions to its ALS program:

New Web Site

On May 1, MDA will launch a new Web site devoted exclusively to ALS. The site, www.als-mda.org, will contain a complete disease description, up-to-date research announcements, current and back issues of The ALS Newsletter, other publications related to the disease, ALS-specific chat rooms and other materials.

In announcing the site, MDA Senior Vice President and Executive Director Robert Ross said that the directors of MDA's 22 MDA/ALS research and clinical centers across the country have been invited to participate in a series of online discussions with people affected by ALS and their caregivers. These online conferences are expected to be scheduled once or twice a month beginning in the fall.

In addition, a new chatroom featuring MDA research on MDA's Web site, www.mda.org/chat/calendar.html, will also begin in May. The inaugural chat, at 9:30 p.m. EDT on May 17, will be led by MDA Director of Research Development Sharon Hesterlee, and will focus on ALS.

MDA's ALS Web site can be reached either directly at www.als-mda.org, or from MDA's main Web site, www.mda.org.

Print PSAs and Legislation

MDA will issue a new set of print public service announcements focused on ALS. The ads will be sent to newspapers and magazines across the country for use year-round.

The Association's National Task Force on Public Awareness has also endorsed the Homebound Clarification Act of 2001, a bill that would change the Medicare definition of "homebound" with respect to home health services (see "Atlanta Man Inspires").

Local ALS Seminars

Across the country, MDA's 180-plus local offices hold seminars for the public on neuromuscular diseases, including workshops and lectures focused on both clinical care and research in ALS. A number of local ALS seminars are planned this year, including several in the western part of the country to be held in May.

For example, at an MDA seminar in Tucson, Ariz., on May 19, Stanley H. Appel, director of the Ronny & Linda Finger MDA/ALS Center at Baylor College of Medicine in Houston, and Hiroshi Mitsumoto, director of the Eleanor and Lou Gehrig MDA/ALS Center at Columbia Presbyterian Medical Center in New York, will present the latest information on ALS.

For a schedule of seminars, watch local MDA newsletters or check www.als-mda.org.  

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MDA LEADS ALS BATTLE WORLDWIDE

Amyotrophic lateral sclerosis has been a part of MDA's program to conquer neuromuscular diseases since the Association's beginnings five decades ago. Having invested well over $130 million in its ALS program, MDA continues to expend three times as much as any other nonprofit, nongovernmental agency for ALS services and research.

When MDA was founded in 1950, only nine years after Lou Gehrig's death, little was known about ALS beyond its name and its devastating power. The disorder has proved to be one of the most baffling to medical science, but with MDA support, researchers have made inroads into understanding its causes and developing effective therapies.

In the mid-1990s, MDA was instrumental in testing and gaining approval of riluzole (Rilutek), a drug that appears to slow the progress of the disorder in some cases. MDA-backed investigators are pursuing many other avenues, which are reported regularly in The ALS Newsletter.

For a list of MDA's programs of services and information for people with ALS, see The ALS Newsletter, vol. 6, no. 1 (February 2001) or visit www.als-mda.org.  

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MDA RAISES EQUIPMENT REPAIR ALLOWANCE

The Muscular Dystrophy Association has increased the annual amount it provides for repairs of wheelchairs and leg braces for people registered with MDA.

The increase from $300 to $500 per person per year is part of MDA's comprehensive program of services for people affected by ALS and other neuromuscular diseases.

MDA also offers its clients assistance with purchasing prescribed wheelchairs and leg braces. Through its local offices, MDA maintains loan closets offering adaptive equipment such as walkers, canes, hydraulic lifts and hospital beds.  

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LOU GEHRIG: PITCHERS FEARED HIS BAT

Light a candle for Lou Gehrig on June 2, or better yet, buy a hot dog at the park and watch a few balls get slammed over the fence, remembering the player who fell to ALS but whose epitaph remained: "Pitchers Feared His Bat."

June 2, coming on the heels of ALS Awareness Month 2001, marks the 60th anniversary of the death of the baseball legend who was known as the game's greatest first baseman, but also as the Iron Horse for his stamina and awe-inspiring hitting power.

Gehrig died in 1941 of ALS. He was 38.

In 1956, Eleanor Gehrig assisted MDA President William Mazer at the ground-breaking ceremony for the Association's Institute for Muscular Disease in New York.

In the 1920s and 1930s, Gehrig distinguished himself as one of the most beloved players on the New York Yankees team and in the history of the game. Among his memorable achievements was his record of playing in 2,130 consecutive games, a streak that remained unmatched for over half a century.

Gehrig, born of working-class immigrant parents in New York in 1903, believed in hard work and family ties. He was a taciturn man and some thought him standoffish because he spoke so little.

But most who knew him remember him as a modest and gentlemanly person — and one thoughtful enough to give serious consideration to the role he occupied in society.

"I'm not trying to pretend baseball players have any altruistic mission in life," Gehrig said, but added: "I think they play an important part in keeping this country out of trouble that it might otherwise be in. When the public is busy discussing pennant races and speculating on who is going to win the World Series, they don't have to work out their natural instincts for excitement by starting a war."

A Career Ends

Gehrig's extraordinary slugging and fielding skills went into a heartbreaking, mysterious decline in 1938. For fear of dragging down his beloved team, Gehrig benched himself in 1939.

Gehrig received a diagnosis of ALS. Although he and his wife, Eleanor, sought the best doctors available, no one could stop the disease's progression.

Gehrig made a farewell appearance at Yankee Stadium on July 4, delivering the world-famous speech in which he declared himself "the luckiest man on the face of the earth" because of the devotion he'd received from friends, family and fans.

Less than two years later, ALS ended Gehrig's life. But for Eleanor, the battle wasn't over.

"After what happened to Lou, I was heartsick and wanted somehow to strike back," she said.

A Crusade Begins

In the 1950s, Eleanor joined forces with a new organization which shared her conviction that ALS must be stopped. It was MDA, the Muscular Dystrophy Association. "Here was the answer to my personal need, people whose thirst for action was as deep as my own," she said.

Eleanor served as MDA's national campaign chairman during crucial formative years in the '50s and '60s. She assisted in chapter development, recruited volunteers including many celebrities, and persuaded radio and television program sponsors to give free publicity to MDA's annual fund-raising campaign.

"The Gehrig legacy is a powerful one for all of us at MDA," said MDA Senior Vice President and Executive Director Robert Ross. "The story of Lou's remarkable grace in dealing with this horrific disease is a touchstone reminding us that thousands of families are undergoing similarly tough battles against ALS right now."

Ross, who worked closely with Eleanor Gehrig, said: "The urgency she conveyed to me in those early days about the need to defeat ALS is something I feel palpably to this day. The fact that MDA has invested over $130 million in ALS research and services over the decades is, in many ways, a tribute to Eleanor's unshakable conviction that answers must and will be found to vanquish ALS."  

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MDA OFFERS CAREGIVER GUIDE

To assist families affected by ALS, MDA offers "When a Loved One Has ALS: A Caregiver's Guide." This 94-page manual is filled with helpful advice for all family members.

If your family doesn't have a caregiver's guide, ask the health care service coordinator at your local MDA office for one. Anyone with a diagnosis of ALS who's registered with MDA can receive one for free.  

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L.A. CONFERENCE OFFERS UP TECH INFO

New products and ideas, some of which may interest people with ALS, were presented at the recent 16th annual Technology and Persons With Disabilities Conference in Los Angeles.

Speakers at the March 19-24 conference, sponsored by the Center on Disabilities at California State University, Northridge, offered information on voice-recognition and eye-tracking technology, "brain-actuated technologies," Medicare coverage of communication devices and related topics.

Voice Technology Frustration

Alan Cantor, president of Cantor Associates, of Toronto, Ontario, gave some tips on making current voice recognition technology more effective.

Cantor, a consultant on workplace accommodation issues, acknowledged that many people become frustrated with the limitations of programs such as Dragon Dictate and IBM ViaVoice. Such programs frequently mishear input, for example.

Dragon Dictate is a popular voice-input system.

"Most people don't use speech recognition in efficient ways, or stop using it," Cantor said. "Some develop vocal injuries."

Cantor suggested that doubling or quadrupling the personal computer's RAM might make the process work better. Also, users should make sure they have good microphones; not all microphones shipped with voice recognition programs are good enough for the job.

He said using the "correct that" command in Dragon Dictate isn't always the fastest way to fix mistakes. Sometimes it's quicker to use "undo" and redictate an entire passage. This is because voice programs often seem to perform better when dealing with whole phrases rather than discrete words.

Also, using such commands as "insert before..." and "insert after..." instead of "move" commands may speed up the revising process.

Cantor also advocated maintaining realistic expectations, adding that users shouldn't expect the voice files to be perfect. "After initial training, a week or so, accuracy will not improve significantly," he said.

Cantor can be reached by calling (416) 406-5098 or by e-mail to acantor@interlog.com.

Eye-Tracking Technology

In a seminar at the conference, rehabilitation professionals compared three eye-tracking computer operating systems.

The experts tested VisionKey, Eyegaze and Quick Glance on such criteria as ease of setup and ease of use. Each system was found to have comparative strengths and weaknesses.

For more information on the study, call the Center for Applied Rehabilitation Technology at Rancho Los Amigos National Rehabilitation Center in Downey, Calif., at (562) 401-6800, or visit www.rancho.org on the Internet.

Cyberlink: Flexing Your Brainfingers

A newer method of hands-free computer access was demonstrated in a product called Cyberlink, from Brain Actuated Technologies of Yellow Springs, Ohio.

This product, formerly called the Mind Mouse, consists of a band strapped around the forehead that manufacturers claim can detect both muscle and brain impulses.

Cyberlink President and CEO Andrew M. Junker demonstrated the interface using an electronic display resembling a bar graph. Each fluctuating color bar represented one of 10 distinct "brainfingers," each keyed to a particular impulse that can be detected by the Cyberlink interface, he said.

The ability to influence particular brainfingers to rise or fall can be translated by a personal computer into the ability to control a mouse, use a Web browser, adjust environmental controls, play a game or perform a variety of other functions, all completely hands-free, Junker said.

Junker, who isn't disabled, initially conceived the Cyberlink interface as a device he could use in hands-free sailing.

Junker said the interface has been used by people with ALS. But he couldn't confirm whether Cyberlink would reliably perform for someone who's lost all voluntary muscle control and relies totally on brainwaves, as could be the case in advanced stages of ALS.

For more information, call Cyber-link at (937) 767-2674, go to www.brainfingers.com, or e-mail to admin@brainfingers.com.

AAC, SGDs and Medicare

Much of the conference focused on augmentative and alternative communication (AAC) devices. AAC is a blanket term for technology that helps people with disabilities to communicate, and includes speech-generating devices, or SGDs.

Medicare now classifies SGDs as durable medical equipment, which means they're eligible for coverage. Before Jan. 2, they'd been considered convenience items.

For more information on Medicare coverage of AAC, go to www.aac-rerc.com or see The ALS Newsletter, vol. 5, no. 6 (December 2000).

Information on next year's Technology and Persons with Disabilities Conference is available from the Center on Disabilities, California State University, 18111 Nordhoff St., Building 11, Suite 103, Northridge, CA 91330-8340; www.csun.edu/cod; or ctrdis@csun.edu.  

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"Long and Winding Road" Leads Beatles Fans and People With ALS to Her Door

Diane Huberty

Diane Huberty of Fort Wayne, Ind., jokes about her "unresolved adolescent Beatlemania." She says, "Like most teen-age girls in the '60s I was a big fan of the Beatles. I left all that behind with marriage, kids, and a career, and it wasn't until their old albums were re-released on CD that I rediscovered them."

As a former neurological nurse now affected by ALS, she shares both her Beatles enthusiasm and her knowledge of ALS via two Web sites.

Huberty's working life began after she graduated from nursing school in 1982. After a couple of years on general medical-surgical units the registered nurse worked for five years in critical care, earning neurological certification.

"Nursing is full of opportunities to help, teach, comfort," she says. "Whether it's taking quick action in an emergency, preventing complications, helping patients and families to understand and cope with illness or injury, or teaching neurology to other nurses, it all comes down to having an opportunity to make a difference, to make a bad situation easier for someone."

When Parkview Hospital in Fort Wayne first opened its neurological unit, she trained nurses to work there. Huberty also spoke at professional conferences, taught evening courses at Indiana University-Purdue, and counseled patients and their families about various aspects of neurological disorders.

By 1985, at age 37, she had received a diagnosis of motor neuron disease, which was later modified to ALS. Her progression was unusually slow, so she was able to continue working for several years with a variety of adaptations. The position of neuroscience educator was less physically demanding, and by using equipment such as leg braces, a walker and an electric scooter, she remained at work until 1995.

Living and Learning

As an educator, Huberty covered everything from anatomy and physiology to injuries and various disorders, including ALS.

"When I first began teaching about ALS, I already had ALS and had studied everything I could find on it," she recalls. "I could teach the anatomy and physiology, diagnosis, disease progression, research, and the textbook version of the nursing care required, but that's what it all was — the textbook version.

"I had not yet progressed far enough to really know the disease from the inside. With every passing year I have learned more of the reality of ALS. My own progression and the information I have gotten via the Internet from other people with ALS and their caregivers has given me a graduate course in ALS — and I am still learning!"

Huberty, 52, now volunteers as an ALS information and resourceperson through the local MDA office, answering questions from those who've just learned they have the disease. At the request of the Fort Wayne MDA office, she recently prepared an in-service session on ALS for an area nursing home, which she offered in writing; because of decreased lung capacity she no longer speaks publicly.

Huberty now uses a BiPAP machine for ventilation and a power wheelchair, and can operate a computer mouse and keyboard independently. An extensive personal support system to help with bathing, dressing and feeding has enabled her do without paid caregivers at home. Her husband, John, who retired early, cares for her during theday. Evenings and weekends are covered by a family friend who shares their home. Neighbors and an adult daughter round out the team.

Connecting With Others

Huberty spends much of her day at the computer, from which she can make telephone calls, operate some electrical appliances, and listen to music or recorded books. Technology also enables her to connect with people from around the globe through her Web sites. In retirement, Huberty taught herself enough computer skills to create and maintain two Web sites.

Her award-winning Beatles site offers visual computer enhancements such as desktop themes and screensavers fashioned after album covers; a full-length fan novel; tidbits about Beatles movies; discussions of lyrics; and trivia related to the Lads from Liverpool.

"I have 'met' people from all over the world. One particularly memorable correspondence was with a high school-aged Beatles fan in [the former] Yugoslavia who was trying to pass the time until the bombing stopped and the schools reopened!"

While the Beatles site nurtures her creative side, Huberty also provides medical information of interest to others living with ALS and their families and friends through both her ALS site and the frequently asked questions (FAQs) section of the newsgroup sci.med.diseases.als. The posted group of about 15 questions changes as new ones are asked, but they cover a definition of ALS, symptoms, diagnosis, treatments, life expectancy and more.

The former nurse says, "Every day I read messages from hundreds of people on newsgroups and e-mail lists, but only send out a few e-mails a day. I explain common medical treatments and simple steps in day-to-day care that can minimize the problems.

"The Internet has given me the opportunity to go on sharing my nursing knowledge and my ever-increasing experiences in coping with ALS so I continue to feel that I can help make a difference," she adds.

You can reach Huberty's ALS site at http://home.att.net/~liveletdie5ALS/home.html and her Beatles site at home.att.net/~liveletdie. The news group sci.med.diseases.als can be found on Internet browsers that support newsgroups by clicking the "sci.med newsgroups" button, then selecting diseases, then ALS. Otherwise, readers can find sci.med.diseases.als via a search engine.  

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Study of Buspirone for Respiratory Impairment Under Way at Two Centers

Researchers at Johns Hopkins University School of Medicine in Baltimore and Massachusetts General Hospital (affiliated with Harvard University) in Boston are studying the drug buspirone to see if it has any positive effects on respiratory function in ALS.

Noah Lechtzin of the Division of Pulmonary and Critical Care Medicine at Johns Hopkins says studies in mice with ALS suggest that buspirone (brand name BuSpar), which is normally prescribed as an anti-anxiety drug, might improve pulmonary function or at least slow its decline in people with ALS.

"Given that buspirone is a relatively safe, widely available, drug for anxiety, we thought it would be a great idea to press on and try it out [in humans]," Lechtzin said.

Lechtzin says the drug's mechanism of action isn't well understood, but it's thought to act on receptors for the central nervous system chemical serotonin. The positive effects on breathing in the mice and a few anecdotal reports of such effects in people with ALS occurred almost immediately after starting the drug, Lechtzin said, while anti-anxiety effects with buspirone normally aren't felt for several weeks.

For that reason, Lechtzin says, he doesn't think the mechanism of breathing improvement — if it's real — has anything to do with relieving anxiety in ALS. "Our thought is that buspirone probably has a more direct neurologic effect [on respiratory function]," he said.

The study will include 50 people with ALS who have only moderately decreased pulmonary function. So far, there are 17 patients enrolled.

If you have ALS, live in the Boston or Baltimore area, can make three visits to the study center, and think you have moderate respiratory impairment without asthma or other respiratory diseases, you can contact Lori Clawson at Johns Hopkins, (410) 614-4346 or (410) 955-8511, or e-mail lclawson@welch.jhu.edu; or call Sarah Hilgenberg at Mass General, (617) 724-4246, or e-mail shilgenberg@partners.org.

The researchers advise that taking other anti-anxiety agents could be dangerous in ALS, since most of them suppress respiratory function. Buspirone is different from all other known anti-anxiety agents, Lechtzin noted.

Results of the trial are expected by the end of the year.  

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MDA-SUPPORTED TOPIRAMATE TRIAL BEGINS AT 20 U.S. CENTERS

Neurologist Merit Cudkowicz at Massachusetts General Hospital in Boston, with support from MDA and the National Institutes of Health, has begun directing a 20-center study of the drug topiramate (brand name Topamax) in ALS. The study involves 288 people with ALS, and recruitment is complete. Each person will take the drug or a placebo (inert substance) for a year, with results expected in 2002.

Topiramate, like riluzole (Rilutek) and gabapentin (Neurontin), partially blocks the action of glutamate, a natural nervous system chemical. However, it does so via a mechanism that's somewhat different from that employed by either of these drugs, Cudkowicz explains.

An excess of glutamate has been associated with ALS. Riluzole has a mildly beneficial effect on ALS survival, and gabapentin was shown to be ineffective.

Cudkowicz says topiramate blocks a molecular "docking site" for glutamate called an AMPA receptor, while riluzole is thought to work on the release of glutamate from nerve cells, and gabapentin is thought to block a docking site called the NMDA receptor.

"This is a different glutamate receptor," Cudkowicz said, noting that good results were seen in mice with ALS that received another AMPA receptor blocker.

There are known side effects to topiramate, Cudkowicz noted, including speech disturbances and difficulty concentrating. But, she said, the drug has been on the market for epilepsy for several years, and, "in the big picture, it has a good safety profile." Side effects were reversible in studies involving people with epilepsy.  

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Connection Between SMN Genes and ALS Getting Stronger

Following on the heels of a provocative mouse study, a new study shows that a gene involved in spinal muscular atrophy (SMA) might be a risk factor for ALS.

ALS and SMA are similar in that both diseases kill the muscle-controlling nerve cells called motor neurons. But while the majority of ALS cases are sporadic — with no clear origin — nearly all cases of SMA are caused by deletion of a gene called SMN1 (for "survival motor neuron 1").

A related gene — SMN2 — acts as a genetic modifier of SMA, meaning that it influences the severity of the disease. SMN2 can partially substitute for SMN1, and, though (like most genes) it's normally present in two copies, it can exist in up to eight copies. In general, having extra copies of SMN2 makes SMA less severe.

A German study in the March 27 issue of Neurology suggests that the SMN2 gene is also a genetic modifier for ALS, and that losing both copies of the gene might pose a risk for developing the sporadic form of the disease. The study also suggests that complete loss of the SMN2 gene hastens the fatal course of sporadic ALS (SALS).

The study examined 110 people with SALS and 100 people with no known disorders, and found that 16 percent of subjects with SALS had deletions in both copies of SMN2, while only 4 percent of control subjects had deletions in both copies. Also, SALS subjects with two intact SMN2 copies lived significantly longer after disease onset (4.2 years) than those with two SMN2 deletions (2.3 years).

The idea that one of the SMN genes might be a genetic modifier for ALS gained favor last year, when MDA grantee Catherine Kunst at Eleanor Roosevelt Institute in Denver showed that a genetic modifier somewhere near the mouse SMN gene affected disease onset in a mouse model of ALS (see The ALS Newsletter, vol. 5, no. 6). (Unlike humans, mice have only one version of SMN.)

The authors of the new study still don't know for sure that SMN2, rather than an unknown gene nearby, is a genetic modifier of SALS. So far, they've only shown that SMN2 deletions are correlated with increased risk and severity of SALS. To determine whether SMN2 itself can actually modify ALS, they're planing to do genetic studies on larger groups of people, and to directly manipulate SMN2 in the mouse model.

Because of its clear role in SMA, boosting the activity of the SMN2 gene is one of the most promising strategies for treating that disease (see "Research Updates" in Quest, vol. 7, no. 6). If SMN2 really is a genetic modifier of ALS, then a similar strategy might be used to treat ALS, the German researchers suggest.  

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AAC and Support Are Keys to Working, Say People With ALS

A recent report by Pennsylvania State University in State College, Pa., on people with ALS who remain employed credits their doing so to the use of alternative and augmentative communication (AAC) systems, along with access to information and occupations that don't require physical labor.

The study by David McNaughton of the Department of Education and School Psychology and Special Education, and Janice Light and Linda Groszyk of the Department of Communication Disorders, surveyed five participants in an Internet focus group. Those surveyed were asked about several aspects of employment: the pros and cons of remaining employed; barriers faced and supports required; and recommendations for others with ALS and for employers, government agencies, and rehab and assistive technology professionals.

Each of the five had received a diagnosis of ALS from one to eight years earlier, and all used assistive technology in their jobs. The two men and three women, aged 50 to 57, were a business magazine writer and editor, a marketing agency account director, a corporate contract negotiator, a school administrator and a pharmacist.

The five gave as reasons for working not only practical benefits, but also feeling useful, gaining a sense of identity and having encouraging experiences. Drawbacks included the physical and emotional toll, along with financial disincentives; physical, technological and attitudinal barriers; and lack of adequate support services.

Their recommendations of practices that would assist AAC users with ALS in maintaining employment included: enforcing current disability regulations; funding and greater availability of equipment and technology; greater awareness and accommodations on the part of employers; early intervention and ongoing support from service providers of AAC; and equipment that's lighter and easier to use. They also advised others to become aware of changes caused by ALS and informed about disability laws and AAC technologies.  

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Two Books Show Clinical, Scientific, Personal Sides of ALS

Robert Brown

Since most doctors have no firsthand knowledge of ALS, they're often ill prepared to help when a patient turns out to have the disease. Amyotrophic Lateral Sclerosis, a new book written primarily for doctors and researchers, supplies an arsenal of information that might help change that.

The editors of the book — among them, Robert H. Brown Jr., MDA/ALS Center Director at Massachusetts General Hospital in Boston — sought out the world's leading ALS experts to compose the chapters. The result is a comprehensive summary of ALS that nicely balances clinical and scientific information.

The first few sections of the book delve into the clinical features of ALS (including rare variants like juvenile ALS), and cover other information important for diagnosis. Chapters describe diagnostic procedures such as electromyography (EMG), brain imaging and transcranial magnetic stimulation (TMS), with figures that illustrate typical results in ALS patients.

Next, a large section on pathogenesis covers research into the origins of ALS. One chapter describes familial cases of ALS linked to the SOD1 gene and other as-yet-unidentified genes, and another describes the transgenic mouse models of ALS. The remaining chapters explore several of the most prominent theories about how ALS destroys motor neurons — from oxidative stress to autoimmunity.

The final two sections deal with therapeutic approaches and patient care. A section about clinical trials in ALS focuses mostly on the negative results of past trials, and doesn't discuss hopeful new treatment avenues like stem cell therapy. On the other hand, the care section (which describes ways to manage the symptoms of ALS) has a refreshing focus on improving the quality of life rather than just prolonging survival.

Overall, the book provides an impressive, up-to-date review of our ever-changing knowledge about ALS — surely a useful tool for any neurologist.

Terminally Sane, by Jay A. Rouelle, 1999. 150 pages, $18. Jarou Publishing, (802) 223-5347, jaroupub@together.net.

Terminally Sane joins a growing list of autobiographical books about ALS.

The author, Jay A. Rouelle of Morrisville, Vt., was an athletic and healthy man maintaining a busy and rewarding life when ALS ambushed him in 1995 at age 34. The book gives a glimpse of his life before his diagnosis, then chronicles the devastation the disease wreaked on his body and his family — but not on his mind, as the title conveys.

Rouelle's journey takes him from deep anger and denial at his prognosis, into despair and thoughts of suicide, and eventually to a quest to stay positive and strong in the face of the disease. Rouelle eventually concludes that the best way he can fight back at the "evil beast" is to write his life story and shine a spotlight on ALS's horror.

Others affected by ALS can likely relate to many of Rouelle's experiences. While struggling with denial of his diagnosis, he searches for a "holy grail" cure through alternative therapies. Later, he's frustrated when a drug study in which he's enrolled is canceled because the drug is deemed ineffective.

Rouelle also examines how the disease caused strain and even the ultimate breakdown of some of his most valued personal relationships.

An especially telling part of Rouelle's book is his description of life in a nursing home, where he moved in 1998. He describes some harrowing encounters with other residents, many of whom had been abandoned by their families. While some of Rouelle's experiences are quite disturbing, others tell of caring, sincere staff and volunteers — some of whom have become Rouelle's dear friends.

Some readers will appreciate Rouelle's honesty about ALS, while those dealing with recent diagnoses might find his frankness too overwhelming.

It's clear that writing the book was a cathartic and fulfilling experience for Rouelle, who, as an amateur writer can be excused for a text that suffers from a lack of organization and abrupt topic transitions within chapters. Unfortunately, the book's dark details overshadow the many valuable messages that he wishes to share. (An example: "Take absolutely nothing in your life for granted.")

Nevertheless, his perspective from inside a nursing home is eye-opening, and the reality of this experience should be of interest to anyone considering such care for a family member.  

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WIFE OF TEXAS FIRE FIGHTER DIES

Dennis Haas, a retired fire fighter from Burnet, Texas, lost his wife, Teresa, to ALS on Feb. 15.

Haas' name may be familiar to readers of The ALS Newsletter from his letter printed in October (vol. 5, no. 5). Haas wrote to urge MDA to keep fighting against ALS and extolled the support given that effort by such organizations as the International Association of Fire Fighters (IAFF).

Haas was a member of IAFF Local 1044 in Abilene for 20 years before retiring.

Haas, in his letter, lamented the fact that it seemed he would have little remaining time with Teresa, 49, because of the rapid progression of her ALS. Unfortunately, that prediction turned out to be all too accurate; she died less than a year after her initial diagnosis in June 2000.

In the letter, Haas said: "The only solace I can find right now in this world is knowing that the efforts of my brother fire fighters and MDA may someday prevent another family from experiencing this horribly emotional experience."  

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'IRON HORSE' FEATURED IN AD CAMPAIGN

According to an April 17 story in USA Today, baseball legend Lou Gehrig's image will be used in a new TV commercial for Alcatel, the French Telecommunications and Internet company.

A representative of the Gehrig estate was quoted as saying Alcatel had licensed the rights to Gehrig's legendary 1939 speech in which he referred to himself as "the luckiest man on the face of the Earth."

The licensing fee paid to the Gehrig estate was said to be considerable. The Eleanor and Lou Gehrig MDA/ALS Center in New York, one of 22 MDA centers nationwide that are devoted to ALS care and research, is a major beneficiary of the estate. Eleanor Gehrig was MDA's national campaign chairperson for many years.  

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HELP FIGHT ALS TODAY AND TOMORROW

Many people who know the devastating effects of ALS are providing lasting support for MDA's battle against the disease. Through your will, you can designate a gift to MDA earmarked to support ALS research or services.

To give what remains of your estate after other bequests have been satisfied, just include the following language in your will:

"I give, devise and bequeath all (or a specified fraction of) the rest, residue and remainder of my estate, whether real or personal, of every kind and description, and wherever situated, to Muscular Dystrophy Association Inc., a New York not-for-profit corporation having its principal office at 3300 East Sunrise Drive, Tucson, Arizona, 85718-3208, for its program of research and services related to amyotrophic lateral sclerosis."

To give a dollar amount or percentage of your estate:

"I give, devise and bequeath the sum of $________ (or ________ percent of my estate) to Muscular Dystrophy Association Inc., a New York not-for-profit corporation having its principal office at 3300 East Sunrise Drive, Tucson, Arizona, 85718-3208, for its program of research and services related to amyotrophic lateral sclerosis."

Your attorney or financial adviser can help you work out the details of a bequest to MDA's ALS Division. For more information, call MDA's Planned Giving Department at (800) 572-1717.  

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