Trials Help Scientists Take Small Steps to Big Goals, New Mexico Director Says

by Margaret Wahl

Paul Gordon examines Karlan Boultinghouse at the MDA/ALS Center at the University of New Mexico.

Paul Gordon is an assistant professor of neurology and director of the Neuromuscular and Degenerative Disease Program at the University of New Mexico School of Medicine in Albuquerque. Last year, he assumed the directorship of the MDA/ALS Center at the university's Health Sciences Center.

Gordon graduated from the University of Arizona College of Medicine in 1992 and did an internship at Columbia University's Roosevelt Hospital in New York, followed by a residency in neurology at the Neurological Institute of New York, part of Columbia Presbyterian Medical Center.

Between 1996 and 2000, he undertook further graduate training, first in neuromuscular aspects of neurology at the Cleveland Clinic Foundation in Ohio, and then in movement disorders at the Neurological Institute.

Q: How did you first become interested in amyotrophic lateral sclerosis?

A: I'm not sure exactly where my interest came from. My dad was raised in New York, and I was always a big Yankees fan. My dad gave me a love of baseball and of Lou Gehrig. The Lou Gehrig story is such a poignant one. He was a great player on a great team in a great city.

Scientifically, my interest in ALS began to grow during medical school when I was exposed to patients with ALS. Then, I was lucky enough to go to Columbia for my residency, where Lewis P. Rowland [an internationally renowned neurologist, who retired in 1998 as co-director of the Eleanor and Lou Gehrig MDA/ALS Center] is an authority on ALS, and it was natural that I gravitated toward him.

Q: In your years of being associated with ALS research, have you developed any theories of what causes ALS?

A: I don't know what causes ALS. Some excellent laboratories across the country are working hard on that question. In some percentage of cases, it's genetic; there's a genetic mutation that causes the death of motor neurons [muscle-controlling nerve cells].

In the majority of cases, it's sporadic [not inherited]. But any hypothesis about what triggers the events that occur in the cell that lead to cell death is speculation at this point. It may be that there's an inherited genetic susceptibility that renders motor nerves vulnerable to some environmental insult.

I believe that this as-yet-unidentified trigger likely sets in motion a cascade of events that leads to activation of stress enzymes and then to cell death pathways. Apoptosis [a type of cell death] and inflammatory processes, or some combination of the two, probably impact ALS, but the pathways have not been completely elucidated.

Q: Tell us about minocycline, an antibiotic that has been one of your main interests in recent years.

A: Minocycline has been considered a potential neuroprotective agent for a while. It may act at the level of the mitochondria [the energy-producing units of cells]. Robert Friedlander at Harvard showed that it prolonged survival in mice with Huntington's disease, where many of the mechanisms of cell death seem to be similar to those in ALS. It's being given to patients with Huntington's disease in a pilot study at Harvard now.

Minocycline has been shown to have benefit in models of Parkinson's disease and stroke, and now in models of ALS. It's been well tolerated in a small study in people with ALS that we conducted [see "Evidence Mounts for Minocycline in ALS," June 2002]. We now have plans to greatly expand that study.

Q: What should people with ALS do in the meantime, while they're waiting for the results of definitive studies like this?

A: You know, research is for the long term. We want to come up with clear and correct answers, so that eventually we get to a legitimate treatment, something that really works. Part of having ALS may be helping other people, maybe even other generations, by participating in good, solid research.

Maybe the other part of having ALS is coming to terms with one's own mortality. We're all up against that — our mortality.

I see a lot of people come to terms with themselves during this disease, and for them, this illness can be, in part, a positive and self-actualizing experience. Many participate in research at the same time. They realize that these are two different goals — the self and other people.

If, 10 years from now, we haven't done the research in a way that gives us very clear answers, then we'll have wasted those 10 years. When I was in training in New York, there was essentially no treatment for AIDS. It was devastating. Now people are living a long time, with treatments.

We can get there with ALS, but we have to design the studies a little better, tighten up the studies, make them cleaner. Then, years from now, we'll have a few positive studies to build on, in the same way that's been done for AIDS.

Q: What do you tell people who are desperate to try something and are afraid that if they enter a controlled study, they might end up in the placebo group?

A: A lot of people ask me about placebos and also about alternative therapies. They say they've only got a short time to live, so why should they risk taking a placebo in a trial? I tell them: because that's the only way we'll get an answer. Study participation is a contribution that the patient can make — turning a bad break around by making a positive contribution.

Many people don't do that. They jump from one thing to another, hoping for an immediate cure. And there are doctors, unfortunately, who will do things just to make money.

It's a mean thing to do to ALS patients, I think. If something doesn't help, we're wasting everybody's time. If it does help, it should be proven and put through the approval process so that everyone can get it. If something works, the Food and Drug Administration [FDA] will approve it, and insurance will pay for it.

Paul Gordon is conducting trials of minocycline in ALS.

Q: Do you recommend riluzole (Rilutek) to your patients?

A: If you want something that has proven benefit, take riluzole. It has a modest benefit, and the FDA has approved it for the indication of ALS.

Most insurance companies will pay for riluzole, but I suggest that, if buying the prescription is a financial hardship, patients consider not taking it because of its modest impact.

Besides money, the other downside of riluzole is that, occasionally, a person taking it will feel lousy, with an upset stomach or a general feeling of malaise. If a person feels lousy with it, it's probably not worth taking. If it were a cure, I'd say it would be worth it.

Q: Tell us a little more about the staff members at your center.

A: We now have a sophisticated, competent team, with a research nurse, who helps with the clinical parts of patient care and coordinates the ALS studies; a research assistant, who does the technical parts of the research and gets everything through the review process; a physical therapist, occupational therapist, respiratory therapist, speech and swallowing therapist, nutritionist and social worker, as well as our MDA services coordinator.

We also have physicians, people we pull in as we need them, who act as consultants for the team, including a gastroenterologist, a pulmonologist, a sleep specialist and a psychiatrist.

Q: What kind of hope can you offer your ALS patients?

A: I tell people that ALS is a very difficult illness, and that right now, part of having ALS is coming to terms with fact that you may die from it. But I also tell them that the only way we'll find a treatment or cure is with solid, controlled studies.

Currently, we have one medication that prolongs life a little bit. With good research, we may find another and start to build on this foundation, buying more and more time. I'm a believer in accomplishing big goals in small steps.

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U.S. House Waters Down Medicare Homebound Amendment

The last chance this year to ease restrictions on people receiving Medicare home health services lies in getting an amendment passed in the starkly divided U.S. Senate.

The David Jayne Medicare Homebound Modernization Act of 2002, named for the Atlanta man with ALS who has led the fight to pass it, would remove restrictions on people receiving home health nursing services who meet certain criteria, including those with ALS. Currently, Medicare home health care recipients can lose their services if they leave their homes for more than brief absences, except for approved reasons.

With talk in the Senate of a last-minute prescription drug compromise bill, at press time Sen. Susan Collins (R-Maine) was watching for a chance to file the Jayne amendment (S. 2085) as an attachment to a viable health care bill. "If we can't include it in one bill, we will try to include it in another," a Collins aide said.

"A hollow victory" is how Jayne described the House of Representatives' version of homebound restriction reform, passed on June 28 as part of the House prescription drug package.

Under current law, people receiving Medicare home health services (in-home skilled nursing assistance with bathing, feeding and other basic functions) may only leave home for "brief and infrequent" absences. New language passed by the House clarifies that absences "such as an occasional trip to the barber or a walk around the block" are permissible.

"This is a huge disappointment to what we were fighting for," said Jayne, who founded the National Coalition to Amend the Homebound Restriction (www.amendhomeboundpolicy.homestead.com), an online coalition of about 13,000 people and 46 organizations, including MDA.

Members of the MDA National Task Force on Public Awareness have also lobbied Congress to amend the restriction.

William Altaffer of Tucson, Ariz., a member of the MDA National Task Force on Public Awareness Steering Committee, added, "A trip to the barber or a walk around the block will do little to end the isolation or improve the quality of life for homebound Medicare patients."

To aid passage of the amendment in the current session of Congress, Jayne urges people to contact their senators or representatives.

Also see Medicare Attempting to Prevent Wrongful Termination of Home Health Care Benefits.

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Online Government Site Compiles Gulf War-Related Research

Three governmental agencies joined forces recently to launch Medsearch, an online library of all federally funded Gulf War-related medical research. The site is a boon to veterans and their families who are searching for possible causes of Gulf War-connected illnesses, including ALS.

The site pulls together the resources of the U.S. Department of Defense (DoD), Department of Veterans Affairs (VA) and the Centers for Disease Control and Prevention (CDC), an agency of the Department of Health and Human Services.

Designed to be scientifically relevant but easy for a layperson to navigate, Medsearch includes topics of particular interest to Gulf War veterans that may not be available elsewhere, such as information about pesticide use and depleted uranium.

Medsearch is located at www.Gulflink.osd.mil/medsearch. Under "Brain & Nervous" in the list of research topics are reports about the governmental investigation into the number of ALS cases among Gulf War vets.

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Telethon to Showcase ALS in Profiles

Two men with ALS — Asa Baber of Chicago and Steven Bishop of Arvada, Colo. — will be profiled on the national broadcast of the Jerry Lewis MDA Labor Day Telethon Sept. 1-2.

Asa and Lou

Asa Baber

On June 19, 1936, the day Asa Baber was born, Lou Gehrig celebrated his 33rd birthday. That year the New York Yankees first baseman had one of his best seasons, finishing with a .354 batting average, 49 home runs, 167 runs scored and 152 runs batted in — good enough to be named league Most Valuable Player.

On July 4, 1939, in what has become one of the most famous speeches in American history, Gehrig publicly said farewell to the game he loved. By the time Asa Baber reached his fifth birthday, Lou Gehrig was gone.

Today, Baber, 66, who writes a column called "Men" for Playboy, is battling the same disease that took Gehrig's life. In his column, from which Baber will read excerpts on the Telethon, he told his readers about having Lou Gehrig's disease:

"I am now confronting the many problems ALS presents, and I know that things will become more difficult for me as the disease progresses," he wrote. "How long it will take is beyond my powers of prediction. But I am ready for whatever comes my way."

Steven Bishop and family

Staying Upbeat

Steven Bishop, 36, also has ALS. And while the disease is slowly destroying his body, this husband and father has refused to let it reach his spirit, or his sense of humor.

It's an attitude that he and his wife, Jennifer, try to impart to others, as they coordinate an MDA ALS support group in Denver.

"They see that we're upbeat and still have a great sense of humor about it," he says. "I think all of that is extremely important."

The Bishops find MDA and the Telethon important, too.

"MDA does a lot of things for me," he relates. "Anytime we can be involved with that is very important because we want (people) to understand that they're not just giving to an organization. We want them to know how it's affecting the people that they're giving to."

Watch your local television listings for the Telethon "Love Network" station nearest you, and tune in on Sept. 1-2. You can also see the Telethon on the Internet at www.mda.org.

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ALS Research Roundup

Avicena Wants to Market Creatine as Orphan Drug

The Avicena Group of San Francisco says it has a creatine product that's much purer than what you can now buy over the counter, and that it plans to market the drug as a specific treatment for ALS.

In February, Avicena received permission from the U.S. Food and Drug Administration to designate its creatine product, NEOtine, an "orphan drug." Orphan drugs are those developed to treat diseases affecting fewer than 200,000 people in the United States or those for which there's no reasonable expectation that development costs can be recovered from sales.

NEOtine is being tested in a multicenter clinical trial in ALS. Trial sites include several MDA/ALS centers, and the MDA/ALS Center at Carolinas Medical Center in Charlotte, N.C., is coordinating the study.

For more information about the trial, which remains open, contact Ruth King, research coordinator at the Carolinas Center, at (704) 355-8699 or ruth.king@carolinashealthcare.org.

If the FDA is convinced that NEOtine is safe and effective in ALS and that it's sufficiently different from available creatine products, it could receive approval as an ALS treatment under the FDA's Orphan Products Program.

"Orphan drug designation is the first step toward final drug approval," said Belinda Tsao-Nivaggioli, vice president of Operations at the Avicena Group. "The next step for us is to meet with the FDA in a pre-IND [investigational new drug] meeting and decide the design of the final, phase 3 clinical trial (if one is needed) before applying for a new drug approval (NDA)."

People with ALS probably will be able to get reimbursement through insurance and government programs if the drug is approved for the disease, Tsao-Nivaggioli said. "Doctors can [then] prescribe this like any other prescription drug."

The Orphan Products Program gives pharmaceutical companies various financial incentives, such as marketing rights, tax credits and assistance with testing.

For details about this trial and other ALS clinical trials, see www.mda.org/research/ctrials.aspx. You can also visit Avicena's Web site at www.avicenagroup.com.

Drug for Emotional Instability Shows Promise

An experimental drug called Neurodex, developed by Avanir Pharmaceuticals in San Diego, has shown promise in reducing emotional instability (lability) in people with ALS.

Many people with ALS experience episodes of unwanted laughing or crying, seemingly unrelated to emotion or external events, a phenomenon that neurologists have attributed to a malfunction in communication between upper and lower motor neurons in the brain and brainstem (see "Study of Emotional Changes Still Open," June 2001, and "Avanir Launches Trial," December 2000). The phenomenon is known as pseudobulbar affect.

Avanir reports that a multicenter trial comparing Neurodex to each of its two components (dextromethorphan and quinidine) showed that Neurodex was more effective than either component alone in reducing the severity and frequency of episodes of undesired emotional expression.

"The data from this study are robust and favor Neurodex over the other treatment arms," James E. Berg, Avanir's vice president of Clinical and Regulatory Affairs, says in a June 20 press release.

Berg told MDA that people with ALS can't obtain Neurodex yet, and trials have ended. Avanir will meet with the Food and Drug Administration in August to discuss the possibility of filing a new drug application based on the study, he said.

Riluzole's Benefits Hold Up Under Scrutiny

A new independent analysis of four trials of Riluzole (brand name Rilutek) has confirmed that use of the drug in ALS has modest benefits.

Rilutek, manufactured by Aventis Pharmaceuticals, is the only medication approved by the U.S. Food and Drug Administration specifically for the treatment of ALS. It became available in 1996 amid claims that it prolonged life in ALS by two to three months and had few significant side effects.

This year, the Cochrane Collaboration published electronically a meta-analysis of four clinical trials of riluzole. Two, conducted in Europe and North America, were the basis for the FDA's original approval and involved more than 1,000 participants. The more recent trials were conducted in Japan and France.

A group of expert reviewers found that riluzole taken at 100 milligrams daily is reasonably safe and probably prolongs survival by about two months in ALS. The reviewers expressed caution that more studies are needed, especially to clarify the effect of the drug in patients over age 75 and in those with advanced disease. Benefits for this group were less clear than in younger, less advanced patients.

Neurologist Robert Miller, director of the Forbes Norris MDA/ALS Research Center at California Pacific Medical Center in San Francisco, was one of the reviewers.

"When all of these data are combined, the therapeutic effect of riluzole still shows a clear trend toward slowing the disease process, but the therapeutic benefit is barely significant and quite modest," Miller told MDA.

"On the positive side, the therapeutic effect confirms the observations in animal models and supports emerging evidence suggesting that glutamate neurotoxicity [toxic effects resulting from an excess or abnormal effect of the nervous system chemical glutamate] is an important mechanism of the disease.

"On the negative side, the drug is expensive ($8,000 to $10,000 per year), and the average prolongation of life is as little as two months, when the data for multiple studies are combined."

The Cochrane Collaboration is an international, not-for-profit organization that aims to "help people make well-informed decisions about health care by preparing, maintaining and promoting the accessibility of systematic reviews of the effects of health care interventions." The organization's Web site is www.cochrane.org, and the Rilutek report can be seen at www.cochrane.org/cochrane/revabstr/g410index.htm (search for "riluzole").

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Beier Fights ALS With Words, Actions and Some Wall Street Friends

by Tara Wood

NEW YORK — Seated in his power wheelchair in a stylish Manhattan apartment, Michael P. Beier rattles off statistics about ALS that he hopes will make people squirm in their seats.

The Beiers: Dustin, Theresa, Michael and Carly

"We have a government that funds only $600 a year per patient" on ALS research, he says. "That's not enough to cover even one visit at the emergency room for my ALS."

A native New Yorker from the Long Island town of Massapequa, Beier describes himself as someone who "could talk the ears off a brass monkey," and he uses his gift for gab daily to raise money and awareness about ALS and MDA's ALS Division.

Beier, 39, who received a diagnosis of ALS in December 2000, speaks out passionately today about the disease, knowing that it could soon take away his ability to talk, as it's done for countless others.

"I want to fight this disease the best I can," he said. "I think in the beginning, my choice was not to be a Christopher Reeve-type guy. But then, I began to look for a certain fund-raiser, or a good direction to go."

Wings for a Cause

He found his direction when he received a flier for a New York fund-raising dinner to benefit MDA's ALS research program. The event, called Wings of Hope, was initiated by Toni Diamond, a Massachusetts woman with ALS, and her husband Warren Schiffer, both former flight attendants for United Airlines.

Beier is director of equity trading for Credit Suisse First Boston and has enjoyed a Wall Street career for 18 years. He rallied support for Wings of Hope from his colleagues and associates in the financial and banking world. When it was held in November, the event attracted more than 800 people and raised $700,000.

Beier is chairman of this year's Oct. 3 event, renamed Wings Over Wall Street and slated to be a cocktail reception at the Marriott Marquis Hotel in New York's Times Square. Its aim is to raise $1 million.

"Through my years in the business, I've been fortunate enough to know a lot of people. Some people don't like me, some people do like me, but they know that I have a deadly disease that is incurable," Beier said. "More than anything it's opening up a lot of eyes."

His role as chairman of the event means he's often on the phone with MDA staff members securing details. Although the fund-raiser "has really taken off with the Wall Street community," he said it will be conducted in the spirit of Toni Diamond.

"Even though she can't talk, walk or breathe on her own, she's still very vital and she's still committed to this disease," Beier said.

Time With Family

Credit Suisse First Boston has been supportive of Beier in many ways. It's sponsoring the Wings event, and many of his colleagues have written personal checks — even into the thousands of dollars — for the cause.

Beier goes to work whenever he's able to, and can motor to his office a few blocks away in his wheelchair. But his employer has been more than accommodating of his needs, he said.

Michael Beier (front) is fighting ALS with the help of many Wall Street business associates.

"They told me that the most important thing to them is to spend time with my family," Beier said. He and his wife, Theresa, have two children, Carly, 5, and Dustin, 3.

"My wife is a tower of strength. She does so much, and she can't do everything but she tries," he said. He added that he sometimes goes to work not only because he loves his job, but to "get out of her hair."

His children "both know that Daddy is sick and Daddy is trying to raise money for doctors to try to find a medicine to help Daddy. They know that I'm going to get worse, and they know that I'm going to need their help more and more," Beier said.

Urgent Message

Beier is also a committee member for Ride for Life and in May took part in the event, in which people with ALS rode wheelchairs and scooters the length of Long Island and into Manhattan to raise ALS awareness.

Beier, an MDA national vice president, is the recipient of the 2002 MDA Personal Achievement Award for the New York Metro area. He's also a member of the Board of Governors at the ALS Research Center at Johns Hopkins University in Baltimore, and a member of the Board of the ALS Committee at Columbia University in New York.

In all his activities, Beier's urgent message about arresting ALS is loud and clear.

"I've always been able to solve a problem. Through my life and through my life as businessman, I've been able to either solve it diplomatically or financially, and now I'm kind of stuck because I can't.

"I can't do it by myself," he said.

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Caregivers: Say 'Yes' to Offers of Help

by Christina Medvescek

"If there's anything I can do to help, just let me know."

Most caregivers have heard that open-ended offer at one time or another from family and friends, but few have actually taken them up on it. Why not, when the job of caregiving is so difficult and time-consuming?

There are several reasons why people don't ask for or accept help, say counselors who work with families of ALS patients. The bottom line: Many people simply are uncomfortable getting outside help, especially if they fear their needs will present a burden. And sometimes the ALS experience is so overwhelming that families feel that no one can help anyway.

But to do your best as a caregiver, you need to answer that offer with concrete, practical tasks, says Kim Wilson, MDA health care services coordinator in Denver.

"Burnout absolutely is a problem," Wilson says. "In our monthly support groups, we reiterate all the time that you need to delegate and take help from people."

Use It or Lose It

Caregivers sometimes say they don't need the help "right now" but will ask when they need it. "A lot of people are trying to put these offers in a savings account," says Meghan Nolan, rehabilitation counselor at the MDA/ALS Center at the Carolinas Medical Center in Charlotte, N.C.

Over time, people tend to drift away, small chores become big ones and the job of caregiving becomes harder. Accepting assistance as you go along can help prevent burnout, keep tasks from piling up, and ensure that people remain connected to your family in supportive ways.

Nolan believes the best time to ask for help is "the earliest time possible. You don't form your army the day before the war. Set your support system of ‘soldiers' in place now so you have the strongest team possible if and when you face a tough battle."

If your family or friends haven't offered to help, there's still a cadre of people itching to pitch in, says Connie Bobo, who cared for her husband, Perry, until his death from ALS in 1993. She wrote about their experiences in On Eagle's Wings: Fulfilling the Needs of Your Terminally Ill Loved Ones (Freefall Factory, 1998).

"All churches have lists of congregational members willing to help with meals, sitting with patients, running errands, etc.," she advises. "A simple telephone call asking for help is all that is required."

Bobo saw firsthand how friendly offers of help dissipate over time. "It is human nature for others to return to their normal way of life — without you," she writes. "Since many of the ‘helping hands' will go away in time, use all the hands of others that you can, while you can."

The Lists

You may want to ask a friend or relative to become your "task coordinator" and match people to jobs. You relay your needs to the coordinator, who finds people to fill them. This cuts down on the amount of asking you have to do, and ensures that no offer to help goes unused.

Do you have "When a Loved One Has ALS: A Caregiver's Guide"? Get this comprehensive, book-length guide at your local MDA office.

Your coordinator can match up helpers with such chores as:

Respite care: Wilson strongly recommends asking someone to come over for an hour or two so you can get a haircut or shop or just sit in the park and watch birds. If your family has children, ask for babysitting or for someone to take the kids overnight occasionally.

Home care: There are many concrete tasks in this category: lawn mowing; weeding and trimming; swimming pool care; painting; taking the car to the shop or changing the oil; washing the dog; minor home repairs.

Daily living: These are the chores that keep you going day to day, such as: grocery shopping; banking; housecleaning and laundry; going to the drug store or post office; getting out the bills; chauffeuring.

Useful gifts: People without much time may prefer to give you something else. Helpful gifts include: a book of postage stamps; sending someone to the house to give a massage, manicure or haircut; a takeout meal; a professional housecleaning; a video or book on tape.

Rather than filling jobs one at a time, cut down on the waiting with a "honey do" letter or a workday.

A "honey do" letter is basically a list of jobs and ongoing needs that's sent to everybody who's offered to help. Be sure to include a contact number and times when it's convenient to come over.

A workday lets you get a lot done and socialize at the same time. Send a letter stating a day, time and chores to be done. At the end of the work session, have a meal together to celebrate friendship and hard work.

Too Much Help?

Some people find they have too much of a good thing. When there are constant visits, it becomes difficult to have private family time.

Nolan says one family put a sign on the front door saying, "Thank you for stopping by and showing your concern. We won't be answering the door or phone from 2 to 5 p.m. while the family is resting. We'll talk with you soon. Your support is priceless!"

Helping is a Blessing

Volunteering not only helps the caregiver, but the helper, too.

"It makes people feel good to be able to help, because they feel helpless," says Kristin Blackwell, clinical research coordinator at the University of Colorado MDA/ALS Clinic. "I want caregivers to see that they are almost doing a favor for the people who want to help."

A valuable resource on getting help with caregiving is Share the Care: How to Organize a Group to Care for Someone Who Is Seriously Ill, by Cappy Capossela and Sheila Warnock (Fireside, 1995).

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26th MDA/ALS Center Opens in Irvine

The University of California-Irvine Medical Center in Orange, Calif., has been designated the site of a new MDA/ALS research and clinical center. The center is the 26th facility to receive the designation.

The new center, to be directed by neurologists Tahseen Mozaffar and John Weiss, is located in the UC-Irvine Medical Center at 101 The City Drive South in Orange. Those wishing to obtain more information or to schedule an appointment at the center should call MDA's office in Orange at (714) 550-0161.

The center provides ALS patients with care from physicians, a nurse coordinator, physical therapist, occupational therapist, speech therapist, a genetic counselor and other professionals.

In addition to its clinical services, the team will also conduct ongoing ALS research.

For a complete list of MDA/ALS Centers, see the May issue of this newsletter or go to www.als-mda.org/clinics/alsserv.html.

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