Evidence Mounts for Minocycline in ALS, With Caution
by Margaret Wahl
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Paul Gordon |
Two laboratory studies of minocycline, an antibiotic in the tetracycline family, have strengthened the case for its possible use as a treatment for ALS. Large human trials are planned.
The drug has already been studied in two small clinical trials in ALS, one at the MDA/ALS Center at the University of New Mexico Health Sciences Center in Albuquerque and another at the Forbes Norris MDA/ALS Research Center at the California Pacific Medical Center in San Francisco.
Paul Gordon, director of the New Mexico center, said he and Robert Miller, director of the San Francisco center, are planning a larger trial to begin late this year or early next year. (Watch this newsletter and the clinical trials part of the MDA Web site at www.mda.org/research/ctrials.aspx for updated information.)
Preliminary results from the two pilot studies, each of which included 20 people with ALS, showed that the drug was, in general, well tolerated. However, some adverse events may have been connected to the drug, including liver dysfunction and a stroke, leading Gordon to caution patients against taking minocycline outside a supervised study.
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| Serge Przedborski |
Clues From Mouse Studies
The laboratory studies were conducted in the United States and Canada, both in mice with ALS.
In the U.S. study, neurosurgeon Robert Friedlander at Harvard Medical School and Brigham and Women's Hospital in Boston, led a team that showed that minocycline helped mice with a genetic (SOD1-linked) form of ALS to live longer and lose function later than did untreated mice.
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| Robert Friedlander |
The team's findings, published in the May 2 issue of Nature, suggest that minocycline works by blocking a key step in the "cell death pathway," a form of cell "suicide" long thought to play a role in ALS development and persistence.
Serge Przedborski, a neurologist and neuroscientist at Columbia Presbyterian Medical Center in New York, was also part of the study team. He and Friedlander have each received MDA funding to study the cell death pathway, also known as the apoptosis pathway, in ALS.
The team found that minocycline blocks the release of the protein cytochrome c from the mitochondria into the cell's main compartment, the cytoplasm. The mitochondria are energy-producing compartments inside cells. Until recently, their crucial role in cell death wasn't fully appreciated.
"This study accomplishes two main things," Friedlander said. "First, it confirms the efficacy in a mouse model of a compound that's approved by the Food and Drug Administration, providing further support for evaluating minocycline in a human trial. Second, understanding how minocycline works will assist in the development of even more effective compounds for ALS."
A parallel Canadian study, conducted at the McGill University Health Centre Research Institute in Montreal, found that minocycline delayed the onset of nerve cell loss and prolonged life in mice with the disease.
That study, conducted by Jean-Pierre Julien and colleagues and published in the June issue of Neurobiology of Disease, emphasizes the anti-inflammatory properties of minocycline rather than its role in slowing the cell death process.
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New Study Explores Connection Between Athletics and ALS
by Dan Stimson
Compared to people with other neurological diseases, people with ALS are more likely to have a history of being athletic and slim, according to a new study from Columbia Presbyterian Medical Center in New York.
The study, presented in April at the American Academy of Neurology annual meeting in Denver, could hold clues to what causes ALS. But it doesn't mean that physical fitness increases the risk of ALS, say the study's main authors, neurologists Lewis Rowland and Nikolaos Scarmeas.
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| Lou Gehrig |
"It doesn't mean that people in general should not exercise or that people with ALS should not exercise," emphasizes Rowland, who served as director of the Eleanor and Lou Gehrig MDA/ALS Center at Columbia from 1987 to 2000.
The real message, Rowland and Scarmeas say, is that future studies should take a closer look at the connection between athletics and ALS, which kills the motor neurons in the spinal cord.
Baseball, Boxing, Football, Soccer …
Hints of the connection have been floating around for years. Boxer Ezzard Charles, baseball player Catfish Hunter and, of course, baseball icon Lou Gehrig all died of ALS.
Three players from the San Francisco 49ers had the disease in the 1980s, and Glenn Montgomery of the Seattle Seahawks lost his life to ALS in 1998. In the last year, the Italian Olympic Committee began investigating an apparent spike in the disease among Italian soccer players.
Rowland says his own ALS patients, many of whom had been athletes or always had been slim, also inspired him to do the study.
He and Scarmeas asked 279 people with ALS or other motor neuron diseases to report their athletic involvement, body type, height and weight prior to their first symptoms. Compared to 152 people with other neurological diseases, people in the ALS group were:
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| Catfish Hunter |
• 1.7 times more likely to have once been varsity athletes
• more than twice as likely to report always having been slim
• 2.5 times more likely to score 25 or below on the body mass index (a measure of slimness) before their symptoms began.
There are several possible explanations for those findings, says Scarmeas, who primarily studies Alzheimer's disease. Athletes might be exposed to more toxins, such as performance-enhancing drugs or the fertilizers used on playing fields, or they could suffer repeated injuries to their motorneurons.
Alternatively, "there could be a [genetic] factor that gives people athletic abilities when they are young and a higher risk for ALS when they grow older," he says.
For now, he cautions, "All of this is hypothetical. The study just provides observations that hopefully will stimulate further research."
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Botulinum Toxin, Radiotherapy Show Promise in Controlling Saliva
Two small studies, one of botulinum toxin (a brand name is Botox) and one of radiotherapy (radiation treatments), have shown some promise in controlling saliva production and drooling in ALS.
ALS-associated drooling occurs often. As the muscles controlling the lips, tongue and swallowing mechanism weaken, saliva pools in the mouth instead of going down the throat (see "Managing Saliva in ALS," October 2001). The usual treatment is medication to dry up the saliva.
The botulinum toxin study included 10 people with ALS and disabling sialorrhea (the technical term for drooling) who had failed to respond to other medications.
Participants received injections of botulinum toxin into both parotids, the saliva-producing glands located on each side of the face near the jaw (see illustration).
Of the eight people who completed the study, seven showed benefit from the treatment.
At two to four weeks after the injections, five people had a "moderate" treatment response, and two had a "marked" response. Responses were measured by the number of tissue papers needed to collect the saliva, subjective reports of function and a quality-of-life scale that sought to assess social disability from drooling. No worsening of swallowing function was noted.
Neurologist Ashok Verma, who sees patients at the Kessenich Family MDA/ALS Center at the University of Miami, was on the study team, which presented its findings at the meeting of the American Academy of Neurology in Denver in April.
The study "showed objectively that this therapy improves excess saliva and drooling and, by doing so, improves the quality of life in this group of patients," Verma said.
The radiotherapy study involved 19 people with ALS who were studied between March 1995 and January 1999 in the Netherlands. Fourteen had complete or partial improvement of drooling within two to three weeks, as reported by the participant, after initial treatment irradiation of both parotid glands.
Ten people reported no side effects. Six had pain in the area of the parotid glands, and four had dryness of the mouth. These effects lasted up to several days.
This study, conducted by Lukas Stalpers and colleagues at the University of Amsterdam, is published in the April 23 issue of Neurology.
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Study to Evaluate Speech Synthesis System Needs Participants With ALS
The Speech Research Laboratory at the Alfred I. duPont Hospital for Children in Wilmington, Del., is seeking people with ALS and their clinicians across the country to participate in a study to evaluate a personalized synthetic speech system for users of augmentative communications devices.
The system comprises software for voice recording called InvTool, software for automatically constructing a speech synthesis database from the recorded utterances, and a text-to-speech synthesis program called ModelTalker. The latter program uses the recorded speech database to produce unrestricted synthetic speech in the user's voice.
The study needs people with ALS who still have the ability to speak and who have personal computers. Under supervision of their clinicians, subjects will download the experimental software, then evaluate the voice-creation process using Web-based surveys.
There's no payment but participants may keep and use the ModelTalker software and synthetic voice they create.
The study organizers are also looking for physicians and speech-language pathologists to collaborate in the study. More information is available by visiting www.asel.udel.edu/speech/clinicians.html or e-mailing tts@asel.udel.edu.
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ALS Marker Study Under Way in New York
Investigators at the Eleanor and Lou Gehrig MDA/ALS Center at Columbia Presbyterian Medical Center in New York have started recruitment for a study of 70 people with ALS and related disorders.
The study seeks to identify disease "markers" — physiologic and structural changes in the nervous system — that can improve the specificity and speed of diagnosis and provide objective criteria with which to measure treatment effects in future clinical trials.
The study, which will involve 50 people with ALS, 10 with the related disorder primary lateral sclerosis (PLS) and 10 with progressive muscular atrophy (PMA), is designed to develop new imaging techniques and physiologic tests. These new examinations will, the investigators hope, provide measurements of changes in the function of muscle-controlling nerve cells (motor neurons) during the course of a neurodegenerative disease.
ALS affects the upper motor neurons, located in the brain, and the lower motor neurons, located in the brainstem and spinal cord. PLS affects only the upper motor neurons, and PMA only the lower motor neurons. These disorders can be hard to distinguish from each other, especially early in the disease course.
Prospective participants will need to be evaluated by neurologist Hiroshi Mitsumoto, center director, or one of his associates.
Participants with ALS will be required to visit the center every three months for 15 months, while those with PLS and PMA will make only one visit. Each participant will receive $50 for each visit.
For further information, contact Maura Del Bene, nurse practitioner and clinic administrator at the center, at (212) 305-5105 or alscenter@columbia.edu.
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Parenthood and ALS — Love Wins Out Over Doubts
by Bill Greenberg
Most parents never forget the first time they held their newborn children. The flood of emotions experienced in that moment ranges from indescribable joy to absolute terror as the reality of parental responsibility sinks in.
While many of those affected by ALS are over 45 at the time of diagnosis and have already had children, a significant percentage of new ALS patients are in their 30s or younger. They may still be undecided about parenthood.
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| Jeff Lester and Daughter Kesley in 1997 |
In February 2001, Kristin Sauer made the journey from her home in Waupun, Wis., to the world-renowned Mayo Clinic in Rochester, Minn. Six months earlier, she'd begun to experience pain and a loss of dexterity in her right hand. She was only 24.
At the Mayo Clinic, Kristin underwent numerous tests to determine the cause of her chronic problem — and to find out why the medicines she was taking for symptom relief were making her nauseated.
That day, doctors dropped a double bombshell on Sauer — not only confirming that she had ALS, but that she was pregnant as well.
Sauer and her husband, Tim, tried to figure out what to do next.
"At first we considered putting the baby up for adoption," Sauer recalls. "Tim didn't know how he could take care of both a wife with ALS and a baby. It was overwhelming."
In October, a healthy Clay Sauer was born.
For his first four months, Clay lived with Kristin's brother and his wife, with the possibility that they'd eventually adopt him. But Kristin and Tim soon realized that she needed Clay — almost as much as her son needed her.
"At first they didn't think it was possible to have him at home," explains Mary Westra, Kristin's mother. "Eventually they realized that they just had to have him in their life — at home and not someplace else."
Love, Life and ALS
Because most people with ALS eventually become quadriplegic, a common misconception exists that someone with ALS is incapable of enjoying an active sex life.
Jeff Lester of Ellisville, Mo., begs to differ.
Lester, 35, received a diagnosis of ALS in October 1993. At first, he struggled with the issue of what to tell his then-girlfriend, Lisa.
"It was one thing for me to decide to fight this disease," Lester explains. "But it was a whole different thing to bring someone you love into that fight."
In the end, he simply told her the truth and let her make up her own mind. They were married in October 1994.
"I cannot imagine battling ALS without my partner, wife and best friend," he says today.
From the beginning, the couple was determined to create a life that was as "normal" as possible. That included talk of having children.
"We were told not to make any long-range plans, and that Lisa wouldn't be able to care for me for very long," Lester recalls. "That was more than eight years ago and we're still fighting ALS together."
As a testament to the Lesters' love for each other, their daughter Kelsey was born in the summer of 1995.
What ALS Doesn't Affect
ALS attacks the motor neurons and primarily affects the voluntary muscles of the body, those that we can move at will.
So while a person with ALS may lose control of all or most voluntary muscle functions, a different part of the nervous system — called the autonomic nervous system — is largely unaffected.
The ability to enjoy sexual relations is among the functions of the autonomic nervous system.
"The reaction of our family and friends at first was excitement followed by the delicate question ‘How?'" Lester recalls.
Today, Lester continues his pursuit of a "normal" life, even though in 1997 he began using a ventilator for respiration.
"I continue to have an active love life," he says.
And the Lesters' second daughter, Emily, is due at the end of July.
More Than Changing Diapers
Kristin Sauer isn't able to change 8-month-old Clay's diapers, though she actively supervises her son's care.
"She holds him and he sits with her and drinks his bottle," Grandma Westra reports. "He's been a real joy."
And while Jeff Lester is physically unable to hug or play with his 7-year-old daughter, it doesn't stop him from being Daddy.
"I have gotten the opportunity to influence her morals and values, and take part in her education," he says proudly. "And we've found our own ways to play together — including me becoming a makeup and hairstyling doll. Our decision to have a child has never been questioned in our minds."
Lester also reports that fatherhood has sparked an interest in genealogy.
"I have been able to trace several family lines back to the 1600s and 1700s because of the Internet and today's computer technology," Lester explains. "I really believe that I will be able to leave the future generations of my family a great gift of their family history."
What Children Need
Becoming a parent isn't a decision to be taken lightly, whether you have a disability or not.
There's no doubt about it: Being a parent is both the most difficult job a person can undertake, and the most rewarding.
In many respects, taking care of a child is a lot like taking care of someone affected by ALS. If you can face each day as a series of logistical challenges, and you have a committed family, it can be done.
But the most important thing a child needs from his or her parents is an almost inexhaustible supply of love.
And love, like sex, is a part of the human experience that ALS can't touch.
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Art Exhibit Travels to Boston
Following the stunning success of its New York engagement,the MDA/ALS exhibit "Transcending Barriers to Creativity: Featuring Artists With ALS" moves to the MDA/ALS Center at Massachusetts General Hospital in Boston this month.
As reported in April, 15 works of art from the MDA Art Collection —all created by artists affected by ALS — are spending the summer touring MDA/ALS centers throughout the Northeast.
The Boston exhibit kicks off with an opening reception from 5 to 7 p.m. June 6 at the hospital's Center for Aging, Genetics and Neurodegeneration, located in the heart of Boston's Charlestown Navy Yard. Guests will have the opportunity to meet Rockport, Mass., artist Fred Siwak, who creates linoleum block prints.
Following the reception, the exhibit will be on display at Massachusetts General Hospital's Wang Ambulatory Care Center from June 7 through June 21.
This powerful exhibit is expected to appear in at least three more MDA/ALS centers before returning to its Tucson, Ariz., home in September.
Another artist with a piece in the exhibit is Erin Brady Worsham of Nashville, Tenn. Four new pieces by Worsham are featured in the June issue of MDA's magazine, Quest, illustrating a group of stories about staying healthy with a chronic disease.
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ALS Prayer Chain Offers Caregivers a Way to Fight
by Christina Medvescek
Many caregivers of people with ALS feel caught in a desperate contradiction. Although they're kept busy with the physical care of their loved ones, they realize there's very little they actually can do against the disease. Slowly and inexorably, despite their best efforts, ALS marches on.
Louise Palumbo of Charleston,W. Va., felt that desperation strongly when her husband, Mario, received an ALS diagnosis in 1993. Mario, then attorney general of West Virginia, was running for governor when his speech started slurring. After the usual run of misdiagnoses, the Palumbos were given a label, a dismal prognosis and little else.
"Many of us [caregivers] have had to become advocates and do research on our own," Louise says. "This is a tough disease to be hopeful about. We need to know that there is something going on, something is happening — whether it ends up in a cure or not — we need to know that there is an effort out there."
Although Mario is immobilized and unable to communicate, Louise hasn't given up her hope for a cure. It's not an easy hope to sustain. To keep it alive for herself and other families coping with ALS, she started a weekly prayer chain to pray for a cure and to pray for ALS patients.
A Powerful Ally
Louise got the idea for a prayer chain after reading about research being done on the healing effects of remote prayer (healing that occurs as a result of being prayed for by others). She felt that prayer — in conjunction with meditation, visualization and conventional medicine — had been a powerful ally in her successful battle against stomach cancer three years ago. So in a small e-mail posting on an ALS Internet message board several months ago, she suggested that people pray each month for a cure.
Response to that single e-mail was small, but like a seed on fertile ground, it steadily grew. First, 10 people in the United States contacted her about joining the chain. Then her minister made the ALS prayer part of his regular Wednesday prayer service, prompting her to switch from once-a-month to once-a-week prayer.
Then an international group, the Self-Realization Fellowship Worldwide Prayer Circle, heard about her idea and added the ALS concern to its weekly prayer circle, which encompasses people in 19 countries.
A Source of Hope
Louise is encouraged by the scope of research into ALS, and she sees prayer as another effort in the fight against the disease — "something that is happening that gives hope."
She admits that at times her hope is small, but it never disappears. The prayer chain "gives me a sense that I am doing something for my husband and something for myself," she says, quoting a philosophy she heard at the MDA/ALS Center at Carolinas Medical Center in Charlotte, N.C.: "I believe in people living with ALS, not dying with ALS."
Louise wants the prayer chain to continue to grow.
"I hope when people read this article, they will join us in prayer every Wednesday, praying for a cure and for people with ALS," she says.
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Jayne Hopes Washington Crusade Will Slay Homebound Restriction
Last month, David Jayne blatantly broke the rules in an effort to change them.
Jayne, who has ALS and receives Medicare home health care benefits, is only allowed to leave his Atlanta home for "infrequent and short" periods, or risk losing his benefits. But the founder of the National Coalition to Amend the Medicare Homebound Restriction (NCAHB) traveled to Washington for almost a week in May to speak at a joint House-Senate press conference and to lobby legislators to support bills that would eliminate that restriction.
"We have some momentum building on the Hill now," enthused Jayne, who was able to meet with a number of key House and Senate aides, policy advisers and members of Congress. He also was interviewed by CNN, National Public Radio and the Washington CBS affiliate television station.
Jayne, who uses a ventilator and can move only three fingers, gave presentations and answered questions using his computerized voice synthesizer.
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| Former Sen. Bob Dole and David Jayne of Atlanta spoke in favor
of eliminating the Medicare homebound restriction during a press conference in May. |
The May 16 press conference also featured Rep. Ed Markey, D-Mass., who sponsored House Bill 1490 to amend the Homebound Restriction; former Sen. Robert Dole (honorary chairman of NCAHB); Henry Claypool, co-chair of Advancing Independence Modernizing Medicare and Medicaid (AIMMM); and Sen. Max Cleland, D-Ga., who co-sponsored Senate Bill 2085 amending the restriction.
About 50 people attended the press conference, including Jayne's two children and Annie Kennedy, MDA's health care services coordinator for the Greater Washington area.
Medicare funding is a hot issue in Congress, and legislators are leery of anything that might increase the budget. Jayne emphasized that removing the restriction wouldn't increase costs, just quality of life.
"Thirty-two years ago when the Homebound Restriction went into effect, the technology for me to be in this room and speaking with you today did not exist," he said at the press conference. "I am not advocating the expansion of the Medicare system. I am only asking that the Homebound Restriction follow in the spirit of the ADA [Americans with Disabilities Act], the Olmstead decision, Ticket to Work and President Bush's New Freedom Initiative."
Jayne founded NCAHB after his home health care benefits were terminated because he traveled to a college football game. They were reinstated when the press took up his cause, and he's gambling on retaining them despite his well-publicized trip to Washington.
"Public awareness and action are crucial to make the Homebound Restriction a thing of the past," he urged.
More information can be found at www.amendhomeboundpolicy.homestead.com.
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Lange to Lead Online Chat
The MDA ALS Division's next clinical-research online chat will feature Dale Lange, co-director of the MDA/ALS Center at New York's Mount Sinai Hospital and Medical Center.
On June 25, from 5:30 to 6:30 p.m. EDT, Lange will cover a variety of ALS-related topics from therapeutic trials and clinical care, to alternative treatments as part of a comprehensive wellness program.
The ALS Division has introduced a new monthly chat for caregivers. Hosted by "cheryl-s," the ALS Caregivers' Chat is held every third Thursday, from 10 to 11 p.m. (EDT).
These and other ALS chats and transcripts can
be found at www.mda.org/chat/calendar.html.
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Mingus Biography Released
Tonight at Noon: A Love Story, by Sue Graham Mingus, 2002, 304 pages, $24. Pantheon Books, www.randomhouse.com/pantheon.
This powerful biography of jazz bassist and composer Charles Mingus serves two purposes for readers with ALS. It's an intimate portrait of the brilliant and difficult Mingus, with insight into how he viewed and created music. The second half of the book details his battle with ALS, which began in 1977 when he was 55 and ended in January 1979.
Written by his widow, the book presents Mingus as initially accepting his diagnosis with good humor. He hated most that it robbed him of the use of his hands and thus his ability to play.
He continued to compose and supervise recordings for some months while his wife, son and many friends pursued every hope for a cure — including injections of unborn lamb and a six-month regimen of herbs and purported surgery by a Mexican healer. He considered suicide; the family discussed mercy killing; in the end his death occurred naturally.
The book candidly depicts the intense relationship between the Minguses and vividly portrays the decline into immobility of a man who "overdid things intentionally. He understood the value of going too far."
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Letters
Profiles Inspire
I wish to thank you for your very informative and inspirational MDA/ALS Newsletter. Knowing that there is so much work and research to find a cure provides the hope for those who have ALS and for their family and friends.
Most of all I enjoy the stories about such people as Dan Beacome, Bill Ross and others. These people set an example for us, that we should keep on with our lives and continue to do things that make us happy and feel worthwhile.
I was diagnosed with ALS in December 2000. I was a middle-school language arts teacher and, because my speech was really bad, I decided to take early retirement. I felt I wasn't being fair to my students if I couldn't talk.
Seeing stories like the ones in your newsletter gave me inspiration to do one thing that I had always wanted to do, but never had the time to do.
Now I spend several hours writing each day. I do it because it gives me purpose and makes me happy. I have written a novel for middle-school kids and several stories, including a picture book. I am busy and content. There is purpose in my life.
June-Gayle Miralles
Miami
Support Stem Cell Research
Within our bodies there is a Taliban attacking our motor nervous system. ALS is our Al Qaeda waging war in a microscopic battlefield. Like our country we need to throw everything we have at our internal enemy or just sit here and wait to die.
That's not what Americans do! When we are backed into a corner, we come out swinging! Like being in a war, we know there will be casualties.
Better an egg that gets destroyed [in stem cell research] that otherwise would end up in the trash anyway than having our lives taken away by this horrible disease. Stem cells are the stealth bombers in our battle.
Robert Kimmel
Confluence, Pa.
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MDA Adds Coverage of Communication Devices
MDA has added to its services program for people with neuromuscular diseases a $2,000 allowance toward purchase of an augmentative communication device.
MDA President & CEO Robert Ross said in mid-May, "We're pleased to be able to provide this important assistance which will enhance the quality of life of those we serve, particularly people with ALS.
"I'm especially pleased to announce this policy during ALS Awareness Month," Ross added.
MDA already provides up to $2,000 in assistance for purchase of a wheelchair or set of leg braces, and allows up to $500 in repair of the equipment.
Those interested in the communication device assistance should contact MDA health care services coordinators in their local offices to find out details of the program. When a device is no longer being used, MDA requests that it be returned to the local office for inclusion in its equipment loan closet.
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