MDA Conference to Explore Clinical Trial Design

Hiroshi Mitsumoto will chair MDA’s ALS Clinical Trials conference in June.

If New York Yankees baseball legend Lou Gehrig were still alive, he’d celebrate his 100th birthday on June 19. But he died in 1941, struck down by ALS when he was just 37 years old and at the top of his game.

Today, as in Gehrig’s day, there’s still no cure for ALS. Although many drug treatments have shown benefits in mice with the disease, only one — riluzole — has passed muster in human trials, and it staves off death by only a few months.

To try to bridge this gap and to mark Gehrig’s 100th birthday, the Eleanor and Lou Gehrig MDA/ALS Center at Columbia University in New York will host ALS Clinical Trials: The Challenge of the Next Century, a scientific conference to be held June 13-15 in nearby Tarrytown. The conference, fully sponsored by MDA, will bring together basic scientists and neurologists who specialize in ALS, as well as officials from the National Institute of Neurological Disorders and Stroke (NINDS).

Hiroshi Mitsumoto, director of the Gehrig center and a member of MDA’s Medical Advisory Committee, will serve as conference chair.

In the past, ALS researchers have considered several possible explanations for the disparate results of mouse studies and clinical trials.

They’ve raised concerns that the mice have a genetic form of ALS, while humans probably have various forms of the disease not suited to a "one treatment fits all" approach. Also, since researchers know that the mice will develop ALS, they often begin treating them before disease onset.

By contrast, people with ALS don’t receive a diagnosis until they show muscle twitching and weakness, signs that the disease has already begun to destroy muscle-controlling nerve cells.

Some researchers speculate that drugs effective in mice might need to be combined in a "cocktail" to work in humans, an idea that’s gained support from a recent study (see "Drug Cocktail," February 2003).

Attendees of the Tarrytown conference will discuss ways to improve clinical research on ALS, including changes in data collection and analysis, identifying early markers of the disease, and testing drug combinations rather than single drugs.

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Cognitive Deficits in ALS Are Usually Subtle

by Margaret Wahl

Benjamin Brooks says it’s important to distinguish between cognitive changes brought about by respiratory abnormalities and those attributable to direct effects of ALS on the brain.

A number of reports in the medical literature, some of which have found their way onto the Internet and into the general press, have suggested that ALS does affect cognitive functioning (thinking) after all. This comes despite more than a century of observation that thinking is well preserved in this disease.

But these findings may have little meaning for people with ALS at this point, says neurologist Hiroshi Mitsumoto, director of the Eleanor and Lou Gehrig MDA/ALS Center at Columbia Presbyterian Medical Center in New York.

"The disease we knew and the disease we know have not changed," Mitsumoto says. "We simply have a greater research armamentarium to detect subtle changes.

"In a strict sense, ALS affects broad areas of the nervous system," he explains. "However, clinically (with respect to experienced symptoms), it is [usually] a pure motor neuron disease."

Mitsumoto says only about 5 percent of people with ALS have significant cognitive difficulties. But when investigators employ highly sophisticated techniques to investigate cognitive and other nervous system functions, they "always find dysfunction in those systems."

And the cognitive deficits in ALS are generally subtle — "not the usual memory deficit that we see in Alzheimer’s disease," he adds.

Minor Changes

Maura Del Bene, an advanced practice nurse and clinical administrator of the Gehrig MDA/ALS Center, agrees with the 5 percent figure for serious thinking impairment in ALS. Most people with ALS who have problems, she says, "have a minor processing change. It’s not an overall memory or decision-making problem."

Following complex, multistep instructions can sometimes pose a challenge, she says. Instructions may have to be broken down into smaller bits.

Neurologist Benjamin Brooks, who directs the MDA/ALS Center at the University of Wisconsin Hospital & Clinics in Madison, says that low blood oxygen levels, especially during sleep, may contribute to the apparent cognitive decline that sometimes occurs in ALS.

The vast majority of people with ALS continue to think and communicate well and often learn to use complex electronic devices if speech muscles weaken.

He says recent studies show that low blood oxygen levels that occur during the night don’t necessarily show up with standard, daytime respiratory testing. Research is needed to discern the difference between cognitive changes due to the disease itself and the "physical changes brought about by the process of ALS," he says.

Because of the recent reports, investigators at Columbia will be among those examining cognitive involvement in ALS. The group will use "a different approach, namely a more physiological, chemical and biological analysis."

In the long run, such studies may lead to better treatment or preventive strategies, Mitsumoto says. In the short run, they may lead to a better appreciation of what families and patients are going through and what, if anything, needs to be altered when professionals and caregivers impart information to patients.

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ALS Online

Chat With the Bishops

In December, the newsletter introduced you to MDA/ALS Division co-chairpersons Steven and Jennifer Bishop of Arvada, Colo.

For the Bishops one of the most challenging aspects of life with ALS (Steven received his diagnosis in March 2001) has been dealing with the implications of the disease for their 4-year-old son, Christopher.

That’s why the Bishops have begun a biweekly chat called PALS With Children. Every other Wednesday, from 12 p.m. to 1 p.m. (EST), you can join Steven ("alsretired") and Jennifer ("alswife") as they discuss the issues related to talking with your children about living with ALS.

The first session of the Bishops’ chat was held Feb. 19. Sessions are scheduled on March 5, March 19, April 2 and April 16.

Time Change for Caregivers Chat

The Caregivers Online weekly chat has been moved to a new time to accommodate the schedules of participants in different time zones. Host "shelia-s" invites caregivers to share everyday successes, frustrations and tips each Tuesday from 7 p.m. to 9 p.m. EST.

For more information and a full schedule of MDA chats, go to www.mda.org/chat/calendar.html.

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ALS Research Roundup

Center Director to Be Part of Large ALS Respiratory Study

Neurologist and neurophysiologist Jeremy Shefner, who directs the MDA/ALS Center at SUNY Upstate Medical University in Syracuse, N.Y., is part of a large study of the respiratory effects of ALS — the most deadly of ALS-related symptoms.

Much of the study will take place at Johns Hopkins Medical Center in Baltimore, to which Shefner will travel at intervals. Hopkins receives MDA funding for ALS research.

Loss of muscle power in the diaphragm leads to serious respiratory impairment, which can be treated with assisted ventilation. Photo courtesy of Respironics

Shefner was selected for the study because he’s among investigators who have developed a technique called MUNE — for "motor unit number estimation" — that counts the number of muscle-controlling nerve cells and the muscle fibers to which they send signals. Each nerve cell and its muscle fibers is one motor unit.

Shefner will apply the MUNE technique as he follows the loss of motor units in the respiratory diaphragms of mice and rats with ALS.

"We’ll record how the diaphragm changes as the animals get ill," Shefner says. "The point of this is to try to identify a marker for respiratory dysfunction that we can use to measure changes."

And the point of that, he says, is to have a way of measuring whether treatments being tested on animals, and eventually, humans, with ALS, negatively or positively influence the respiratory course of the disease.

No human trials are planned for the immediate future, but such trials are the ultimate goal of the research, Shefner says. He notes that safety issues will be worked out in the rodents first.

Minocycline Trial to Change Slightly

A study to test the effects in ALS of minocycline, an antibiotic in the tetracycline family, will begin this summer at 16 centers across the country. Minocycline has shown promise in tests in mice with ALS and in a small study of people with the disease.

Paul Gordon

Neurologist Paul Gordon, who currently directs the MDA/ALS Center at the University of New Mexico Health Sciences Center in Albuquerque, will become associate medical director of the Eleanor and Lou Gehrig MDA/ALS Research Center at Columbia Presbyterian on April 1 and will direct the minocycline study from there.

Neurologist John Chapin will replace Gordon as director of the MDA/ALS Center in Albuquerque.

For information about participating in the minocycline trial, contact Nayra Gad, project coordinator, at Columbia Presbyterian at (212) 305-3985 or ng152@columbia.edu.

This is new contact information, replacing that in the November 2002 issue of The MDA/ALS Newsletter.

Neuronal Stem Cells Found in Blood

Researchers have discovered that human blood contains cells capable of becoming nerve cells (neurons).

The finding is the latest advance in the search for stem cells that might be used to replace or repair neurons lost to diseases like ALS.

Recent studies have shown that adult bone marrow contains stem cells capable of forming neurons and other cell types, raising hopes that bone marrow transplantation could be used to treat ALS and other diseases. But even the harvesting of bone marrow stem cells carries concerns: The procedure involves administration of drugs that can cause significant discomfort to the donor, including muscle pain and joint pain.

In a new study, Eliezer Huberman and his team at Argonne National Laboratory in Argonne, Ill., show that stem cells from circulating blood can be induced to form several cell types, including skin cells and neurons.

Blood could be used as an "easily accessible source" of stem cells for transplantation, they write in the Feb. 26 online edition of the Proceedings of the National Academy of Sciences.

Anti-HIV Drugs Investigated for ALS

In late January, newspapers in Ontario reported that a local woman with ALS saw her symptoms improve dramatically after 18 months on a drug cocktail used to combat HIV, the virus that causes AIDS.

The woman, who is HIV-negative, began taking the cocktail after her neurologist, John Turnbull, read two studies describing AIDS patients who developed an ALS-like syndrome and then recovered from it with similar treatment (see "HIV Link," October 2001).

Turnbull, who directs an ALS clinic at McMaster University Medical Center in Hamilton, Ontario, is now conducting a clinical trial of the drug cocktail, formally known as HAART or highly active antiretroviral therapy, in 15 people with the disease.

MDA has discussed working with Turnbull on future trials of HAART for ALS.

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WHY RUN FOR ALS? IT’S PERSONAL

by Stu Green

It’s cold, it’s raining, it’s late, it’s exhausting, it’s painful. And those are the plusses. And we haven’t even mentioned dogs.

So, why do you do it? Why do you run? And why do you make the calls, make the e-mails, make the letters and make your case for MDA? Why all the work for a group most people probably only think about once a year around Labor Day?

Why?

That’s not a question I can answer for you. Each person supplies his own on this quiz. I can only offer my own answer.

Like many of you, I’ve thought about running the Boston Marathon for a while. And, to be honest about it, getting an official number was a huge incentive to join the Miracle Marathon Team. But it went further than that.

For me, it hit home.

My Reasons

My brother, David, and his wife, Jean, raised their two sons in Rochester, N.Y. It was an existence they loved — complete with a suburban house with a vegetable garden, well-behaved children and plenty of Little League games.

About four years ago, David, then 43, was playing tennis with one of his sons. He was having trouble getting to the ball. He knew something was wrong, and it was. ALS — a three-letter acronym for tragedy and tears.

Stu Green (left) with his brother, David, in 1993

The next three years were horrific for David as he slowly lost his ability to walk, to move at all, to talk, to eat.

It wasn’t a hard decision for me to run Boston in 2001 and 2002. And it wasn’t a hard decision for me to go out and run in the cold, the ice and everything that goes along with New England winters.

After a while, my brother was confined to a wheelchair. Although it wasn’t the place he wanted to be, it was an amazing chair that cost $30,000.

So, when I asked people to donate to MDA, I truly appreciated the donation. They weren’t giving it to some nameless, faceless organization. It was going to help a person. It was going to help my brother.

Many times, on many cold runs on silent, dark streets next to a field or woods, I heard noises behind me. I turned around, and no one was there. I knew, in that moment, they were echoes, echoes of some very good people helping me to keep going, helping me to help my brother.

It was a long battle, but my brother quietly slipped away on July 31 of last year. He was 46.

Your Own Reasons

So, what’s your answer to the question? You probably don’t have one yet. If this is your first, second or 10th Boston, the answer changes, and it changes us. It’s a running commentary, if you will, on our lives.

So, this is my message for this year’s Miracle Marathon team:

There are some amazing people among us. You don’t have to look far.

To an onlooker, a pack of 15,000 can look like that — a pack. But each person has a story to tell, a life to live. A race to run.

The word "hero" has been bandied about so that it’s a hollow image of your former self. Chuck Norris, Arnold, Indiana Jones, the classic heroes? Perhaps. But, really, a hero is one person who makes a difference in one other person’s life. Quietly. Consistently. Always there.

You know who I mean, don’t you?

It’s not that they don’t stumble. They do. That’s not the point. The point is, they get up again. And again. And again if they have to.

They keep going. They get it done.

They’re there.

From my family, thank you all for being there. You do make a difference.

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Benefits of Service Dogs to Be Studied

Diane Collins, occupational therapist and graduate student at the University of Pittsburgh, is conducting a phone and mail survey to determine whether service dogs enhance functional independence, promote psychosocial well-being, or improve socioeconomic status for people with disabilities.

Collins will compare the status of people who have service dogs with that of people who either aren’t seeking a service dog or who are waiting for one.

For more information, contact Collins at dmcst84@pitt.edu or (412) 365-4544. You can also phone Shirley Fitzgerald, assistant professor in the university’s School of Health and Rehabilitation Sciences at (412) 365-4840.

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Missouri Minister Delivers Opening Prayer for U.S. House

by Tara Wood

As leader of the Community Christian Church in Camdenton, Mo., the Rev. Tracy Carroll is accustomed to heeding the call of a higher power.

But in January, a call came from Washington, D.C., that also garnered his attention.

On the phone was the office of the Chaplain of the U.S. House of Representatives, inviting Carroll to give the opening prayer in the House the following week.

It was a once-in-a-lifetime honor for Carroll, who received a diagnosis of ALS in 2001, and serves as co-minister of the church with his wife, Colleen.

Carroll, 44, was selected for the honor after church members Billie Huddleston and Richard Derringer contacted their representative, Ike Skelton, and told the Congressman about the Carrolls’ many contributions to their community.

A Whirlwind Trip

One whirlwind week later, with Colleen’s help, Tracy climbed steps to the podium and delivered a prayer. His words became a recorded part of history as they were included in the day’s Congressional Record, and were taped by C-SPAN.

"Grant assurance of the goodness of people across this great land as we face various concerns in this generation. In gratitude for institutions of democracy, grant courage to stand and to build consensus," Carroll prayed before the legislators.

The trip included more than the average amount of Washington activity and security, as Carroll addressed the House on the morning after the president delivered his State of the Union address.

From left, Rep. Ike Skelton; Rev. Daniel P. Coughlin, chaplain of the U.S. House of Representatives; Rev. Tracy Carroll; and Rev. Colleen Carroll.

In fact, the Carrolls arrived at their hotel two blocks from the Capitol just a half hour before the president’s speech.

They were greeted by "helicopters, jets, police, Secret Service, blockades and checkpoints…. How did they know we were coming?" Tracy joked in his church newsletter.

Other highlights of the trip, for which the Carrolls paid their own expenses, included lunch and conversations with Skelton and other members of Congress, a unique look behind the scenes of Washington and impeccable hospitality along the way. (And, yes, Carroll also noted the irony of the inaccessibility of the House’s podium to congressional staff members with disabilities.)

"I found Congress to be a very hospitable place. That surprised me a bit," he said. "In the hallways I sensed real collegiality and real concern for the nation — across the aisle. It wasn’t just party battling that we see all the time."

Before his presentation, Carroll had to submit the prayer for approval by the Chaplain’s office to be sure it adhered to certain guidelines.

Prayer leaders are guided "to encourage the congressmen and women and also to remember that the nation is under God. They encourage you not to delve into foreign policy or domestic policy," Carroll said, adding that this was challenging since he and his wife have been "rather outspoken" against the prospect of war with Iraq.

"As I prepared the prayer, I felt God gave me the things that I needed to say at a time like this, and I tried to pray faithfully in that direction," he said.

A Congregation Gives Back

The event was one of several ways in which church members have shown their appreciation and empathy to the Carrolls as Tracy battles ALS.

He now wears leg braces and uses a cane when he walks. His hands and arms have been weakened, and his breathing is affected by the disease, he said.

"The wheelchair is coming, I can see it," said Carroll, whose father and grandfather died of ALS.

Just after they returned from Washington, the Carrolls moved into a home that would accommodate a wheelchair since the parsonage wasn’t accessible.

They purchased the home with the help of $50,000 in contributions from members of the church and the community (Camdenton is a small resort town of about 3,000 on the Lake of the Ozarks.)

The community has also donated a voice-activated computer, and funds so the family can take a vacation before he needs to use a wheelchair full time. Friends are putting together a care team for the time when his medical needs become more complex.

"There are men in the church that literally help me get upstairs, and the church has been so wonderful in moving us," Carroll said. At some point Tracy will take disability leave, and Colleen will continue as pastor.

"I’m very humbled by all the honors I’ve received, and I’m overwhelmed by the reciprocal love that I’ve received from the community and the church that we serve here. It’s just a wonderful group of people," Carroll said.

Contribution to Research

Carroll is also committed to doing his part for research seeking a cure for ALS. He participates in an MDA genetic study of ALS at Northwestern University and in a double-blind study of the drug Celebrex at the MDA/ALS Center at Washington University School of Medicine in St. Louis.

Despite a three-hour drive each month to St. Louis, participating in the study helps keep the Carrolls from feeling "detached" because there are few treatment options for ALS, Colleen Carroll said.

"Through the monthly visits because of the study, we still feel very connected and very informed and, in fact, cared for," she said.

Meantime, the Carroll family — which includes Nathaniel, 17, and Tabitha, 13 — is recording a music CD of faith-based songs.

While Tracy Carroll continues to care for his congregation, he’s deeply honored that his congregation is now taking care of him and his family — so much that he doesn’t dwell on having ALS.

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ALS Doesn’t Masquerade As Lyme Disease, Experts Say

Recent items in The ALS Digest, an online publication, have suggested that the tick-borne, bacterial infection known as Lyme disease can mimic ALS and that new tests can tell the difference between these conditions with certainty.

But can this infectious disease actually be confused with ALS? And, if you do get a positive result on a Lyme test, can you be assured you don’t have ALS?

Not likely, experts say.

ALS involves dysfunction of upper motor neurons (the nerve cells that run from the brain to the spinal cord) and lower motor neurons (the nerve cells that go to muscles). This dysfunction is detected by physical exam and electrical testing.

"The selective involvement of upper and lower motor neurons, sparing other nervous system structures, is the hallmark of ALS," says neurologist David Chad, who directs the MDA clinic at the University of Massachusetts in Worcester, in the heart of Lyme disease country. "That’s not typical of the neurological complications of Lyme disease."

A red rash with a clear center, resembling a "bull’s eye," is common with Lyme disease. It has a set of symptoms different from those of ALS.

Lyme, Chad notes, "has the tempo of an infectious disease. Although there are chronic forms, Lyme disease usually presents as an infection, with a rash, followed by fever, headache, limb pain and malaise."

In contrast, he says, ALS, in the vast majority of cases, "is painless, comes on over months, and is not accompanied by a systemic component."

Allen Steere, a rheumatologist at Massachusetts General Hospital in Boston and an expert in Lyme disease, says a new blood test for Lyme, known as the VlsE, isn’t any better than slightly older tests at detecting Lyme disease in someone who is far enough into it to have neurologic symptoms.

There are "false positive" results with Lyme disease tests, Steere says, because they aren’t completely specific for the disease. Newer tests may even show more false positives, he says, than the testing procedure now recommended by the Centers for Disease Control and Prevention.

Only once in his long career has Chad ever found it advisable to treat a patient for Lyme disease when he thought the problem was much more likely to be ALS. That, he says, was a special case, in which the Lyme disease treatment proved essential for the family’s peace of mind.

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Infection Derails Test of ‘Brain Communicator’ in Activist Jayne

by Christina Medvescek

David Jayne, the Georgia man with ALS who spearheaded the fight against the Medicare homebound restriction for people receiving home health care, has been leading a different kind of fight against being locked in by paralysis from ALS.

Jayne, 41, underwent surgery at Gwinnett Medical Center in Duluth, Ga., in October to have an experimental Brain Communicator implanted in his brain. He hoped the device would allow him to control his personal computer via his thoughts.

The revolutionary device, created by Neural Signals of Atlanta, uses implanted neurotrophic electrodes to detect brain activity and translate it into commands that control computer software.

David Jayne, seen here preparing to fly to Washington last year, hopes to try the Brain Communicator again.

Although the electrodes appeared to be transmitting, Jayne never had a chance to learn to use them to operate his computer. His scalp incision refused to heal over the accompanying hardware, putting him at risk for serious infection. The hardware was removed in mid-January, but the electrodes were left in place.

Jayne says he’s regained most of his strength and endurance since the surgery, and still has partial use of two fingers, as well as most of his facial muscles. He’s now using another Neural Signals product, the Muscle Communicator, which allows a user to operate a computer mouse by means of extremely minor muscle movement from any part of the body.

Jayne hopes to have the Brain Communicator hardware reinstalled once his scalp has fully healed.

"What have I got to lose?" he says. "ALS will soon paralyze me totally. I have children to raise and work to do."

Jayne’s surgery was paid for by the National Institutes of Health because of its experimental nature. Neural Signals is developing its technology in partnership with several entities, including the National Institute of Neurological Disorders and Stroke, five universities and the Veterans Administration. The company can be reached via www.neuralsignals.com or (404) 872-5757.

Jayne, who heads the National Coalition to Amend the Medicare Homebound Restriction (www.amendhomeboundpolicy.homestead.com), invites people to contact him about the new devices at djayne23@ aol.com.

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Foundation Offers Free Computers

The Beaumont Foundation of America will be giving computer equipment to low-income people with disabilities over the next five years.

BFA will provide $350 million worth of Toshiba brand equipment with Internet capability.

The foundation will give away almost 2,000 technology packages this year to people living in the District of Columbia and these 21 states (Group A):

Alabama, Alaska, California, Colorado, Hawaii, Idaho, Illinois, Kansas, Mississippi, Montana, Nebraska, New Mexico, New York, North Dakota, Oregon, South Dakota, Texas, Virginia, Washington, West Virginia and Wyoming.

Applications from people in Group A will be accepted until March 31.

In 2004, people living in the remaining 29 states (Group B) will be eligible to apply.

Anyone interested in applying for a grant can call the foundation at (866) 505-2667, or register online at www.bmtfoundation.com.

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