ALS RESEARCH ROUNDUP
Gulf War Report Available Online
The Research Advisory Committee on Gulf War Veterans’ Illnesses has published online its full report, originally released in September.
You can read it at www1.va.gov/rac-gwvi/docs/ReportandRecommendations_2004.pdf as a pdf file, requiring Adobe Acrobat software.
The report includes 152 pages of analysis and recommendations concerning symptoms experienced by U.S. military personnel deployed during Operation Desert Storm in 1990 and 1991.
Some of the findings follow.
Many who served in the Gulf War were exposed to a variety of potentially toxic substances during their deployment. Among these were several neurotoxins — chemical nerve agents, medications taken to protect troops from anticipated effects of poison nerve agents, and several types of pesticides. All these belong to a class of compounds known to adversely affect the nervous system.
All or most of the chemical agents to which the soldiers were exposed counteract the enzyme acetylcholinesterase, which normally breaks down the chemical acetylcholine. Acetylcholine carries signals in the nervous system and from nerve to muscle cells. Prolonged and excessive acetylcholine signaling is proposed as a possible source of nervous system damage in Gulf War participants.
Gulf War veterans differ from a healthy control (comparison) group on measures of neurological pathology and impairment. Gulf War veterans have developed ALS at twice the rate of their nondeployed counterparts.
Contrary to previous assumptions, exposure to nerve agents at levels too low to produce acute symptoms can result in chronic adverse effects on the nervous and immune systems.
Congress should allocate at least $45 million for research on Gulf War illnesses, to be divided among the Departments of Veterans Affairs, Defense, and Health and Human Services.
"We need to study more specifically these agents that were used," says Hiroshi Mitsumoto, co-director of the Eleanor and Lou Gehrig MDA/ALS Center at Columbia University in New York. "There are a number of questions we need to answer."
Report Shows Tamoxifen Safe, Maybe Beneficial
An interim analysis of an ongoing trial of the breast cancer drug tamoxifen (Nolvadex) in 60 people with ALS demonstrates that the drug appears to be safe and may even improve survival in the disease.
Benjamin Brooks, a neurologist who directs the MDA/ALS Center at the University of Wisconsin at Madison, received funding from MDA and the National Institutes of Health to test tamoxifen, after a patient of his who had both ALS and breast cancer, for which she received tamoxifen, maintained muscle strength for more than four years.
Participants in three groups who took high-dose tamoxifen combined with the ALS drug riluzole (Rilutek) showed a four- to six-month survival advantage compared to the two groups who took a low dose of tamoxifen plus riluzole. The low-dose groups showed survival similar to that seen in people treated with a placebo (inert substance) in other ALS studies.
There were no significant side effects.
Brooks reported these preliminary findings in Philadelphia last month at the 15th International Symposium on ALS/MND, organized by the Motor Neurone Disease Association. The study hasn’t yet been completed.
High-Dose CoQ10 Looks Safe in Long-Term Study
MDA research grantee Merit Cudkowicz, at Massachusetts General Hospital in Boston, announced at last month’s ALS symposium in Philadelphia that her study of 31 people with ALS who took a high dose — up to 3,000 milligrams — of coenzyme Q10 for eight months tolerated the drug well. The only side effects were gastrointestinal and were considered mild.
The dietary supplement is thought to improve the function of the mitochondria, the energy-producing units inside cells.
In August, researchers at Columbia University Medical Center in New York reported similar results in their study of the safety and tolerability of coQ10 in ALS, but that study was shorter and used lower doses.
The National Institute of Neurological Disorders and Stroke of the National Institutes of Health has approved funding for a multicenter study of coQ10 in ALS that will include MDA/ALS centers at Columbia and Massachusetts General.
For information about this study, which is just getting under way, contact Alexandra Barsdorf (212) 342-3026 or aib2104@columbia.edu.
VEGF Protein Infusion Helps Rats With ALS
Vascular endothelial growth factor (VEGF), a protein that appears to promote blood vessel growth and protect nerve cells, continues to show promise in laboratory experiments in rodents.
A Belgian and Dutch scientific team found that delivering the VEGF protein (for which the VEGF gene provides instructions) into the brains of rats with ALS showed significant benefit. The team was led by MDA research grantee Peter Carmeliet, of the University of Leuven and the Flanders Interuniversity Institute for Biotechnology, both in Belgium.
Such a strategy might provide a shorter route from laboratory to clinic than would a gene-based therapy, which has to go through more regulatory steps.
The investigators, who published their findings online Nov. 28 in Nature Neuroscience, found that injecting the VEGF protein into a fluid-filled space (ventricle) in the rats’ brains delayed paralysis and prolonged survival.
In rats genetically destined to develop ALS, paralysis appeared 17 days (16 percent) later in rats who received VEGF at two months of age than in those treated with fluid alone.
Both groups of rats developed the disease, but the treated rats lived 22 days (18 percent) longer.
Rats that received VEGF treatment at nearly three months, after symptoms had already appeared, lived 10 days (8 percent) longer than their untreated counterparts.
"In summary," the authors write, "our data indicate that VEGF may assist in slowing down [nerve cell] degeneration and warrant further studies to clarify the relevance of VEGF delivery for the ALS community."
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MORE WORK TO BE DONE
Rices Begin 2nd Term as Co-Chairs
by Alyssa Quintero
"As long as we have no cure, there is more work to be done."
With that in mind, Christopher and Reda Rice of Houston have accepted an invitation to serve a second term as co-chairpersons of MDA’s ALS Division.
The couple’s mission remains clear — to communicate to the public the urgent need to find a cure for ALS, and to urge donations to support MDA’s worldwide, scientific effort to eradicate the disease.
"If we can help raise awareness about ALS, give hope to those with ALS and raise money for research, we will be a step closer," Reda said.
"The expectations and goals remain unchanged," Chris Rice said. "Bringing awareness to this disease will in turn help raise money. Raising money will aid in the research and development of drugs and therapies, which will bring a cure."
Promoting Awareness
In 2004, the Rices appeared on the national broadcast of the Jerry Lewis MDA Telethon, and they were featured in MDA’s national ALS public service announcement campaign (video and print). They gave several newspaper and television interviews, and participated in many MDA events.
The Rices, who have three children, Tori, 8, Mason, 6, and Shelby, 5, also wrote a frequent column for the MDA/ALS Newsmagazine.
Last year, Reda and Chris met countless people, and based on those experiences, they agree that their family is no different from most others who deal with ALS.
"We find we have to balance the reality of this disease without losing hope, and I feel most others who are living this life do the same thing," Reda said. "It is truly amazing to meet one family after another who continues to move on with a positive attitude and hopeful outlook on life."
Life in the Spotlight
Chris, 39, received a diagnosis of ALS in October 2001. The neuromuscular disease has slurred his speech and affected his strength and mobility. Chris continues to work for Lincoln Property Co., a Houston management firm.
"For all that is being done for me to find a cure, I feel that it [serving as co-chair] is the least I can do to help," Chris said.
While it’s been difficult getting used to life in the national spotlight, the Rices are up to the challenge in 2005.
"It is worth the lack of privacy to know that we are doing something to help make a difference, by raising awareness and money so ALS will eventually never have to be a part of people’s lives," Reda said.
Searching for Information on ALS and Caregiving?
When cruising for ALS information online, check out these Internet sites for caregiver information, resources and support:
Support Programs and Services
Caregiving Across the States (www.caregiver.org ; check "What’s New") allows you to search for information about caregiver support programs and services in each of the 50 states, including links to relevant state agencies and programs. It’s the result of a two-year "State of the States" study by the National Center on Caregiving at the Family Caregiver Alliance, in collaboration with the National Conference of State Legislatures.
The full report (also available at the site) examines government-funded caregiver support programs since the passage of the National Family Caregiver Support Program in 2000.
MDA Information
Articles from the MDA/ALS Newsmagazine,
transcripts from chats with ALS experts
and answers to "Ask the Experts"
questions are available online at www.als-mda.org.
Enter your search topic in the "Search Our Site" box for links to MDA information on such topics as leg swelling, falling, Lyme disease, clinical trials, research, caregiver assistance, constipation, government benefits and much more.
The MDA/ALS site also offers other MDA publications on ALS. When a Loved One Has ALS: A Caregiver’s Guide covers such topics as the stages of ALS, hygiene and skin care, nutrition and swallowing, exercise, respiratory care, communication, and meeting psychological and emotional needs. Print copies of the guide are available through MDA offices.
Connections
"Living with ALS," a chat for people with ALS and their caregivers, is held every Monday at 4 p.m. Eastern time, hosted by Jeff "ragingbear" and Geoff "geoff." Go to www.mda.org/chat/calendar.html.
Suggestion Box
Have you learned a good trick for turning over in bed? Found a creative way to deal with excess saliva? Is there a topic you’d like to see addressed?
Contact the MDA/ALS Newsmagazine with tips you’d like to pass along to others, at publications@mdausa.org. And continue to watch this newsmagazine for important information for those caring for loved ones with ALS.
FACE-OFF ON MULTIDRUG TRIALS
To Do or Not to Do?
by Margaret Wahl
Two highly respected neurologists, both of whom direct MDA/ALS centers, can disagree — and they’ve done so in back-to-back opinion pieces in the November issue of Muscle & Nerve. The controversy is over whether or not to use drug "cocktails," combinations of pharmaceuticals, each of which hasn’t necessarily proven itself alone, in ALS clinical trials.
Jeffrey Rosenfeld, who directs the MDA/ALS Center at Carolinas Medical Center in Charlotte, N.C., is conducting such a multidrug trial. (It’s now closed to enrollment, with results expected this year.)
In his study, participants take eight drugs from five drug classes. There’s no placebo (inactive substance) group, but patients take the drugs using different delivery systems, such as from separate bottles or partitioned boxes.
The study’s purpose is to look at safety and the feasibility of giving people 32 pills a day, either by mouth or via a gastrostomy tube, Rosenfeld said, and not to measure efficacy.
No Straight Lines
Rosenfeld says multidrug combination trials are needed in ALS because the pathways that lead to the death of muscle-controlling nerve cells (motor neurons) are "very complex and not necessarily in straight lines."
He adds, "There’s more than one way for motor neurons to degenerate. If several mechanisms leading to cell death are in place concurrently, if you were to interrupt any one pathway, it’s still likely that there are other, parallel pathways by which cells could continue to die."
In addition, Rosenfeld notes, ALS is "perhaps not just one disease. We worry a lot about the fact that patients with different types of motor neuron disease may have different underlying physiology."
Aiming at multiple targets, he says, is necessary when you know there’s more than one involved and you don’t know which one is the most important in each patient.
"It’s reasonable to say that the chance of hitting meaningful targets certainly is greater when you intervene at multiple levels," he says. "It would be incredibly optimistic to think that any one drug would have a specific enough, potent enough benefit to create the kinds of treatment effects that we look for in available drug trials."
On the Other Hand…
On the other side of the drug cocktail question is Jeremy M. Shefner, director of the MDA/ALS Center at State University of New York Upstate Medical University in Syracuse.
"Scientifically it has no merit," Shefner says of current drug cocktail studies in ALS. Scientists can’t tell which drug was responsible for any benefit detected in such a study, although he admits that may not matter to everyone. Still, he says, "Patients want to know what works; they don’t generally want to take a zillion things."
Shefner says the question of whether ALS will ultimately be treated with combinations of drugs is entirely different from whether combinations of unproven drugs should be tested now.
"If you’re asking if it’s very likely that ALS will be treated by drug combinations, yes, of course, I’m a proponent of that," he says. "But if the question is whether people should take a bunch of things that show no efficacy in human beings" his answer is different. "You don’t just combine them," he says.
Shefner says that, although a justification for multiple drugs in ALS has sometimes been that such combinations are used in cancer treatment, he thinks this comparison has no meaning for the current state of affairs in ALS.
"We do treat cancer with multiple agents that have synergistic effects," he says, "and I suspect that we will be treating ALS with synergistic agents. But the way cancer drugs have evolved has never been to put drugs with unknown effects together. Individual drug activity has been demonstrated and then added to a previous treatment."
Unknown Risks
In his editorial, Shefner notes that combinations of drugs can expose patients to increased risks of side effects, the possibility that drugs will counteract and nullify each other’s effects, and increased costs for treatment.
For Rosenfeld, the possible benefits outweigh the risks. "It’s a little bit counterintuitive, the premise that underlies multidrug therapy, but it’s that drugs that individually do not show benefit might show benefit when you put them together."
Given the many disappointments in ALS clinical trials, it’s time, he says, to "think out of the box.
Equipment Corner
Get Time on Your Side When Obtaining Major Equipment
by Tara Wood
People who receive a daunting diagnosis of ALS often also find themselves weathering a blizzard of information and paperwork concerning vital choices they have to make about coping with the disease.
Add in a mountain of details about pricey equipment that you may or may not need someday, and it doesn’t take much to get overwhelmed.
But foresight and realistic planning can make time your ally and stave off frustration when it comes to obtaining items that can greatly affect your quality of life.
This article offers a realistic timeline for obtaining three major pieces of equipment you’ll likely need during the course of ALS. This information should help you to avoid hassles.
Note that experts consulted echoed each other on one clear point: It’s never too early to start the process of obtaining these items. They also advise working with qualified experts who are familiar with ALS and have experience working with Medicare and other insurance providers.
Another tip: Persistence pays, said Debbie King, a health care services coordinator for MDA’s ALS Division in St. Louis. King advises MDA clients not to be shy about routinely calling a dealer to inquire about the status of an order, and to be assertive.
Power Wheelchairs
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Companies like Permobil offer a range of power wheelchair styles.
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Price: $8,000 - $35,000
Time Line: The average time between ordering a power wheelchair and starting to use it is three months, according to King, who surveyed several MDA clients with ALS.
That time usually isn’t spent at the manufacturer’s end, says one major wheelchair company.
"On average, our wheelchairs can be put together in multiple configurations normally within two days," said Anjali Weber, clinical education specialist with Permobil.
Custom or out-of-stock items may take a few days more, she said.
Most of the time is taken up by obtaining prior authorization from Medicare, insurance companies or other funding sources.
Holdups & Hurdles: Paperwork, paperwork and paperwork.
To get insurance coverage for a power wheelchair, doctors and equipment dealers must fill out forms with appropriate codes, and answer very specific questions to show the device’s "medical necessity." Dealers aren’t allowed to coach doctors on how to answer questions, Weber said.
"If the CMN [certificate of medical necessity] is not filled out or not correctly filled out then a chair will be denied," she said, and the paperwork process has to be repeated.
A previous purchase of a manual wheelchair or scooter through your insurance company may also hinder the later purchase of a power chair, Weber said.
While such equipment may have value to your lifestyle, keep in mind that medical necessity has to be justified for each item, as will why one type of equipment no longer meets your needs.
"That’s why it’s so important not to use the insurance money for the less expensive equipment," Weber said.
Advice: Some equipment dealers will proceed with a sale before prior authorization is determined, and that can save time.
Also, investigate MDA loan closets as a way to try out various chairs before you buy, or as a means to tide you over while you wait for your own equipment to arrive.
Keep long-term needs in mind and select a chair with as many features as possible that will benefit your health. Plus, always make sure that the chair you select will fit into your home or other places where you intend to use it, Weber said.
Communication Device
Price: $2,500 - $10,000
Time Line: It can take from three to six months to obtain an augmentative, alternative communication device, King said, depending on the type of device and your insurance carrier. Fortunately, Medicare and other insurance companies have begun paying for these devices in recent years.
You also may need additional time to learn how to use the device, as many are computerized and use advanced technology.
Holdups & Hurdles: Again, it’s the paperwork. As with wheelchairs, every feature on a communication device has to be medically justified, King said.
According to the Web site for DynaVox Systems, a major manufacturer of communication devices, most funding sources require a speech evaluation, doctor’s prescription and letter of medical necessity.
Advice: Work with experts, such as speech-language pathologists, who are familiar with ALS.
Several manufacturers have funding departments dedicated to securing payment for their products, and will file your claims for you. The DynaVox Web site states that its funding coordinators are "aware of the coding and authorization guidelines that most insurers use."
Again, MDA loan closets can let you try out this equipment, and don’t forget that MDA will pay $2,000 toward the one-time purchase of a communication device.
Accessible Vans
Price: $20,000 - $50,000, depending on features
Time Line: Anywhere from one day to a month and a half.
Lowered-floor minivans are growing especially popular and are often readily available on many mobility dealers’ lots.
If you know exactly what type of van will fit your wheelchair, parking area and lifestyle, "it is possible to have a van delivered in a day’s time," said Marcus Smith, owner of Access Vans in Grosse Tete, La.
A more customized van may require a month or more, said Smith, a member of the National Mobility Equipment Dealers Association.
However, more time should be spent doing research about the type of vehicle that will meet your needs now and in the future, MDA’s King said. There are numerous choices and features to consider. They’re outlined in "When Your Plan Is a Van" in MDA’s magazine Quest, March-April 2004.
Holdups & Hurdles: A major problem in the adapted vehicle industry occurs when customers go to ordinary car dealerships first. Too often, a customer who hasn’t done enough research will unknowingly purchase a van that can’t be adapted with assistive gear such as ramps or lifts.
"That salesman is going to tell them anything to sell them a car on their lot," Smith said. "Then we [mobility dealers] have to tell them the bad news that we can’t do anything with that vehicle."
A mobility dealer will look at the wheelchair user’s size, abilities, the number of people they usually travel with, and more to find the right vehicle to fit an individual’s needs, Smith said.
Price can be a big challenge for individuals with ALS who have a limited income. However, some mobility dealers offer 10-year financing packages, and have ideas for finding funding help.
Some dealers have a consignment policy that will help you resell a converted van down the road, Smith said.
Advice: Smith stresses that van shoppers should involve a mobility dealer from the start, whether you intend to drive the vehicle and need an evaluation, or are purchasing a vehicle elsewhere to be adapted.
Again, keep an eye on the future: One van may fit a smaller manual chair or scooter, but be sure it will accommodate a bigger power wheelchair down the road, Smith said.
Equipment Corner, a new regular feature of the MDA/ALS Newsmagazine, will highlight assistive equipment and new technology of relevance to people with ALS. If you have a topic, item or question about any type of equipment or device that you’d like to see addressed, please let us know at publications@mdausa.org.
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New Book Covers Anatomy to Insurance
Amyotrophic Lateral Sclerosis, by Robert G. Miller, M.D.; Deborah Gelinas, M.D.; and Patricia O’Connor, R.N.; 246 pages, 2005, $22.95. American Academy of Neurology Press and Demos Medical Publishing, www.demosmedpub.com.
Want to know the anatomy and physiology underlying ALS? How the disease is diagnosed? What tests need to be done and what they mean? What clinical trials are all about? How to treat symptoms and live better? How to negotiate the insurance maze?
You’ll find answers to all these questions and more in this highly readable book by Robert Miller, who directs the Forbes Norris MDA/ALS Center in San Francisco; Deborah Gelinas, clinical director at the center; and Patricia O’Connor, the center’s nurse manager.
It’s part of the American Academy of Neurology Press’s Quality of Life Guide series, and is addressed to people with ALS and their families.
MDA Research Administration Director Ronald Schenkenberger has also contributed a chapter, describing MDA’s long history in ALS research and patient care. Registered dietician Alycia Chu, clinical psychologist Susan Levine, and speech therapist Amy Roman are among the other expert contributors.
The book contains a thorough index and a list of products and information sources of interest to people facing ALS.
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