ALS Research Roundup
Study suggests Gulf War-associated increase in ALS is time-limited and correlated with location

by Margaret Wahl

Military personnel who spent significant time in Saudi Arabia near the Kuwaiti border in 1990-1991 had the highest estimated risk of developing ALS.

U.S. veterans of the first Gulf War don’t have a permanently increased chance of developing ALS, according to a study supported by the Department of Veterans Affairs and the Department of Defense and published online June 6 in Neuroepidemiology.

“Basically, the outbreak has run its course,” said Ronnie Horner, a professor at the Institute for the Study of Health at the University of Cincinnati and an author on the study. “The excess risk appears to have dissipated.”

Horner, with colleagues at other universities and at Veterans Affairs Medical Centers, compared the incidence of new ALS cases that occurred between 1991 and 2001 in two groups: 700,000 military personnel deployed to the Persian Gulf region in 1990-1991, in whom 48 cases occurred; and 1.8 million people who were in the military during that period but weren’t sent to the Gulf, in whom 76 cases occurred.

They found those who didn’t go to the Persian Gulf region in 1990-1991 had a low incidence of ALS compared to the average risk for men in western Washington state during this entire period; but that those who served in the Gulf region showed a consistently higher incidence of ALS compared to average Washington state men and to the non-Gulf-deployed military population during some of those years.

The incidence of new ALS cases steadily increased among Gulf-deployed personnel between 1994 and 1996, about four to six years after deployment, peaking in 1996, after which it declined. By 2001, their risk was the same as for the non-deployed military personnel and below the risk for the male Washington state population in general.

The data suggest there were specific exposures or other events associated with the first Gulf War that, perhaps in combination with genetic susceptibility factors, led to a temporary rise in ALS cases.

“We have to keep a very open and creative mind here,” Horner said. “It may not be any single exposure or single factor. It may be multiple exposures to multiple agents.”

In another study, published online in Neurotoxicology June 20, Marie Lynn Miranda at Duke University, and colleagues, analyzed troop movements in the Gulf region during the war to see if they could determine whether being in a particular location influenced a soldier’s chance of incurring an elevated ALS risk.

They determined that military personnel who spent significant time in Saudi Arabia near the Kuwaiti border had the highest chance of an elevated ALS risk. A soldier who spent 126 days (about four months) in this area would have twice the average risk of developing ALS, the investigators concluded. (Even an elevated risk still yields small numbers of ALS cases. On average, about two people out of every 100,000 will develop ALS in a given year. Twice that would mean four people.)

In March 1991, U.S. Army units destroyed munitions depots in Khamisiyah, located in southeastern Iraq near the Kuwaiti and Saudi Arabian borders. Later, when these bunkers and warehouses were found to contain chemical weapons, the Department of Defense determined some 100,000 soldiers may have been exposed to low levels of nervous-system toxins.

The study team, which included Ronnie Horner, who was also part of the Neuroepidemiology study analyzing the duration of elevated ALS risk, emphasizes that no particular toxic exposures have yet been linked to the development of ALS in Gulf War veterans and that this latest study only suggests a geographic correlation.

However, they say, exposure to the munitions depots in Khamisiyah and to smoke from oil-well fires are candidate risk factors that are consistent with the location data. They note that further studies should attempt to correlate troop locations with exposures and other candidate risk factors.

“The next step is to see whether there is a time dimension to the risk associated with specific geographic locations; that is, is a specific geographic location at a specific time associated with an elevated risk of ALS?” Horner said. “For example, we need to know whether the troops who developed ALS were in the same location at the same time that the oil-well fire smoke plumes or the low-level nerve- agent plume were present.”

ALS TDI finds lithium ineffective, apocynin ambiguous in ALS mice

The ALS Therapy Development Institute (ALS TDI), an MDA-supported laboratory in Cambridge, Mass., announced results of mouse studies of lithium and apocynin July 11.

ALS TDI scientists found no benefit from lithium in ALS mice. However, investigators caution that a negative result in the mouse doesn’t necessarily predict one in humans.

The ALS TDI’s independent study of lithium indicated no observable survival or functional benefit in the ALS mouse.

John McCarty, treatment investigator at the ALS TDI, said he was confident of the mouse results but that "the value of using the mouse model tool is not necessarily to conclude a therapeutic can't work in humans; such a determination can really only be made with proper clinical trials."

The ALS TDI team also conducted two ALS mouse studies of apocynin, a molecule that interferes with damaging byproducts of cellular metabolism.

The ALS TDI scientists compared disease progression in ALS mice that received apocynin starting at day 50 (late start) and then at day 30 (early start) to progression in control (untreated) ALS mice.

The scientists didn’t see indications of strong efficacy in the mouse model, but they did see a weak trend toward extension of survival in female mice that started on apocynin at age 30 days. The trend didn’t reach statistical significance, but the Institute plans to repeat the early-start study.

VA broadens ALS care coverage, while studies of veterans continue

On July 14, James Peake, Secretary of Veterans’ Affairs at the U.S. Department of Veterans Affairs, announced the Department will broaden its coverage of ALS as a service-connected disability for all veterans, not just those who served in the 1990-1991 Gulf War. Peake informed lawmakers of his decision on a conference call.

The U.S. Veterans’ Affairs Department recently announced that ALS will be covered as a service-connected disability for all veterans, not just those who served in the Gulf War.

A study of all veterans with ALS is now under way, utilizing data from the National Registry of Veterans with ALS, established in 2003 by the U.S. Department of Veterans Affairs. (The Registry closed in September 2007.)

The new study, Genes and Environmental Exposures in Veterans with ALS (GENEVA), will compare records and DNA samples from veterans with ALS to data from veterans without the disease to evaluate the contributions of genetic susceptibilities and environmental exposures to the risk of developing ALS.

Silke Schmidt of Duke University Medical Center in Durham, N.C., with colleagues from Duke, the National Institutes of Health, and other institutions, described the study’s methodology online April 18 in Neuroepidemiology.

MDA-supported lithium study now open at 10 sites

An MDA-funded, 100-person study of lithium carbonate in ALS is now open at 10 U.S. centers. The new study will be open label, meaning there will be no placebo (inert substance) group. Trial sites are in San Francisco, Los Angeles, St. Louis, Philadelphia, Houston, Salt Lake City, Scottsdale (Ariz.), Orange (Calif.), Kansas City (Kan.) and Portland (Ore.). For details and contact information, see the clinical trials section of the MDA Web site.

Umbilical-cord blood cells may have therapeutic potential in ALS

An intravenous infusion of human umbilical-cord blood cells significantly extended the life span of SOD1 mice, which have an ALS-like disease, as well as prolonged their motor function and decreased biochemical evidence of inflammation.

Svitlana Garbuzova-Davis, at the University of South Florida in Tampa, with colleagues there and at Saneron CCEL Therapeutics in Tampa, tested three different dosage levels of human cord-blood cells in the mice and then compared these mice to SOD1 mice receiving no treatment or treatment with cyclosporine, an immunosuppressant drug.

Mice receiving the moderate dose of cord-blood cells showed a 15 percent decrease in disease progression in terms of measured motor function at certain time points, and they lived more than 20 percent longer than either untreated or cyclosporine-treated mice.

Mice treated with this most effective dose of cells also showed significantly less evidence of inflammation in the central nervous system, as measured by biochemical and cellular tests, than untreated or cyclosporine-treated mice.

Results from mice receiving the other two doses of human umbilical-cord blood cells weren’t much different from those of the untreated or cyclosporine-treated mice on most of the tests.

The investigators, who published their findings in the June issue of PLoS One, say they believe their results demonstrate that treatment of ALS with human umbilical-cord blood cells at the right dose might have a protective effect on degenerating neurons (nerve cells) by dampening harmful inflammatory and immune-system responses in ALS.

“Developing an effective treatment for ALS is complicated by the diffuse nature of motor neuron death,” said Garbuzova-Davis, referring to the large areas of muscle-controlling nerve cells affected in this disease. “However, cell therapy may offer a promising new treatment.”

Garbuzova-Davis has MDA funding to study barriers between the bloodstream and nervous system in ALS.

FDA approves diaphragm pacing system to treat people with spinal cord injuries

The U.S. Food and Drug Administration (FDA) has approved the NeuRX Diaphragm Pacing System for patients with spinal cord injuries who lack voluntary control of the respiratory diaphragm, opening the door to greater future availability of this device for people with ALS.

The NeuRX system provides paced electrical stimulation to the diaphragm muscle and the nerve fibers that run through it. When stimulated by surgically implanted electrodes, the diaphragm contracts, mimicking natural breathing by allowing air to flow into the lungs. The system is designed to partially substitute for or replace a positive-pressure ventilation device, which forces air into the lungs through a mouthpiece or other interface.

The NeuRX diaphragm pacing system stimulates the diaphragm to contract and descend, allowing air to flow into the lungs.

NeuRx’s manufacturer, Cleveland-based Synapse Biomedical (see www.synapsebiomedical.com), announced the FDA’s approval June 17, noting the agency’s decision was based on studies of the system in 50 patients with spinal cord injuries since 2000.

A study of the pacing system in ALS is being conducted in Cleveland, Baltimore and Stanford, Calif. (See “Diaphragm Conditioning with Motor Point Stimulation” under Clinical Trials on www.mda.org.)

If you’re in the study, the device itself is free, but the associated surgery and care are not. These costs are about $5,000, which in some cases may be covered by private insurance. These costs are also eligible for coverage under Medicare Part B. See the Synapse Web site’s ALS Reimbursement section, or contact the company at (440) 774-4043, for details.

MDA/ALS Center directors produce collection of articles about ALS

Greg Carter and Michael Weiss, co-directors of the MDA/ALS Center at the University of Washington Medical Center in Seattle, are the editors of the August issue of Physical Medicine and Rehabilitation, which is devoted largely to ALS. The articles, many of which are written by MDA/ALS Center directors, cover a wide range of topics, such as genetics, quality of life and pulmonary support. The issue is available through the publisher’s Web site at www.us.elsevierhealth.com for $99 or by calling (800) 654-2452.

Lights! Camera! Roll 'em!

by Kathy Wechsler

Scott Lew, left, directing a “Bickford” scene on location with actors Patrick Fugit and Olivia Wilde.

During his Hollywood career, Scott D. Lew of Van Nuys, Calif., has been a writer, producer, director, actor and star of the 2007 documentary, “Living with Lew.”

Lew, 39, has worked on films such as “Spy Game,” “Air Force One” and “Bring It On.” He produced and directed documentaries including “Fan Club” and the award-winning “Welcome Sinners! The Velvet Hammer Story.”

In addition, last season he wrote for USA Network’s show, “The Dead Zone.”

Take 2

In 2002, just as Lew was getting the finances cleared to begin directing his first feature film, “Bickford Shmeckler’s Cool Ideas,” the twitching in his arms and chest muscles was diagnosed as ALS.

Soon after, he began having trouble using his hands and walking, falling frequently. About a month before his crew began filming “Bickford Schmeckler,” Lew began using a wheelchair full time.

“I just embraced the idea of becoming a ‘wheelchair dude,’” says Lew. “I do think it helped me, in a strange way, as a director. When someone is in a wheelchair, you need to bend down and focus on what they’re saying — perfect for a director who wants people’s attention.”

Filmmaker Scott Lew

Movie sets aren’t designed to be navigated by wheelchairs, but Lew says his crew was very helpful moving obstacles and clearing pathways. To deal with the Hollywood summer heat and long, grueling hours, Lew had an assistant to help him drink, take restroom breaks and lie down to use his BiPAP machine.

Because it was his dream to direct “Bickford Schmeckler,” for which he’d written the script four years earlier, Lew says quitting was not an option. He’d worked too hard climbing the Hollywood ladder to let ALS stop him from fulfilling this dream, and so dedicated himself to working long hours despite his ALS progression.

“I was nervous that the people who were financing the film wouldn’t want me to direct it given my rapidly deteriorating condition,” he says. “Luckily for me, they embraced the idea, and after some legal maneuvering to ensure there would be a director in place just in case I couldn’t complete the film, we went full steam ahead.”

Take 3

Before filming began, Lew was approached by Adam Bardach, a friend with whom he worked on “Welcome Sinners: The Velvet Hammer Story.” Bardach asked Lew about making a documentary about his life with ALS.

“I remember him saying, ‘A guy like you, in your condition, making a movie, is a great subject for a movie in itself,’” recalls Lew. “I’m a big ham, so any time someone says they want to follow me around with their camera, I’m powerless to deny them.”

Produced by Bardach, “Living with Lew” follows Lew as he directs, copes with ALS with the loving support of friends and family, and learns to adjust to breathing machines, feeding tubes and transfer lifts.

Lew’s unique personality and self-confidence bring an uplifting spirit to the documentary that surprises many viewers, says Bardach.

“The point that ‘Living with Lew’ is trying to make is that you have a choice to deal with adversity in a positive way or in a negative way, and I think Scott was such an incredible example of dealing with it in a positive way,” says Bardach, who hopes the documentary will help raise ALS awareness.

Take 4

Lew hasn’t slowed down one bit since the making of “Living with Lew.” He played the “Wheelchair Guy” in a 2008 episode of “Reno 911” on Comedy Central and was a guest speaker at the Southern California MDA/ALS Awareness Month seminar in May, where he had the opportunity to introduce “Living with Lew” to attendees.

Currently, Lew is working on a documentary about Lou Gehrig and writing a memoir about his “crazy Hollywood journey” called “Scott Lew’s Hollywood, Deadly.” And he’s doing all that while trying to sell a television show, a thriller with comic overtones.

“As I progress and lose abilities, I’ve got ‘Living with Lew’ and ‘Bickford Shmeckler’s Cool Ideas,’ to remind myself to look on the bright side,” says Lew, whose speech has deteriorated since the making of the documentary.

“It’s not impossible to have fun with ALS, you just need to choose to do it.”

To learn more about “Living with Lew,” visit www.livingwithlew.com.

Low-tech, Low-cost Assistance for Daily Living

by Bill Norman

Some of the living costs associated with ALS have big price tags (power wheelchairs being a prime example), but many low-cost aids are available to make daily around-the-home activities easier for both caregivers and people with ALS.

Ingress and egress

Two big challenges for people in wheelchairs are fitting through doorways and traversing abrupt changes in elevation, like thresholds and curbs.

For the first situation, a doorway width of 36 inches usually is sufficient for wheelchair traffic. However, an open door may infringe on doorway space because of the way it’s hinged to the doorframe. Up to 2 inches of doorway width can be gained by replacing standard hinges with offset door hinges. They’re available at hardware stores, medical supply houses and online for about $12 per pair.

Make thresholds wheelchair-navigable with threshold ramps made of lightweight aluminum or rubber. Ramps start out at about $40 for models that can handle a 1-inch threshold, and go all the way to versions able to accommodate a 6-inch rise (about $200).

Transfers, such as from a wheelchair to bed or toilet, require less exertion with some form of transfer device. One low-tech version is a pivot disk (about $50), which essentially is a “lazy Susan” capable of holding 300 pounds. Caregivers place the disk under the seated person’s feet, raise the person to his or her feet onto the disk, then pivot the person and lower to the new location. Check medical supply stores and online.

Let there be light

A touch lamp converter (about $25) modifies lamps so they turn on or off by a mere touch to any metal part of the lamp. The device is particularly helpful for those who have difficulty gripping and turning a switch. Converters attach easily to existing lamps, and also make regular bulbs function as three-way bulbs. Available at local hardware and home improvement stores, as well as online.

In most homes, wall light switches are out of reach for people in wheelchairs, especially if arm mobility is compromised. One way to overcome the reach challenge is with a wall light switch extension handle (about $8 for a package of two).

Handles are slender lengths of clear plastic that attach to standard toggle switches and extend downward 12 inches. Screws and bushings for installation are included. Check hardware and home improvement stores, and online.

TV remote controls

Extra-large-button universal remotes (around $25) are easier to manipulate than standard remotes with small, tightly-clustered buttons. Some models light up for easy visibility. Check the electronics departments of local stores, as well as online.

Sartorial assistance

Trying to button clothing — shirt, blouse, trousers or what have you — can be exasperating. To avoid tangling with those contrary little contraptions, consider using Velcro button aids (about $20 for a package of 10). They look like regular buttons, but hold garments closed with just a small amount of pressure on the hook-and-loop fabric. Check sewing departments of local stores or online.

Rub-a-dub scrub

If muscles don’t feel like cooperating, getting clean can be a chore. Long-handled bath products, available at local bath stores, bath departments and online, can help wash backs, feet, hair and other hard-to-reach places. Prices usually run under $20. If rigid-handled bath sponges don’t give adequate performance, try a sponge with a bendable handle that can be custom molded by hand (usually after warming it up).

Mobile storage

One capability that most wheelchairs lack is storage space for the user’s belongings. Packs that attach to the wheelchair back often are hard to reach. Get around the problem with a wheelchair armrest pouch (around $25). Available in a variety of materials including fleece, these handy pouches keep necessities close at hand. Check medical supply stores as well as online.

Controlling cuisine

Food sometimes has a habit of escaping the plate if the diner’s hand control is uncertain. Plate guards are a good way to avoid that problem. Available either in plastic (about $10) or stainless steel (about $13), these semi-circular guards attach to the edge of a regular plate and provide help loading up a spoon or fork with food. Plate guards — and adapted plates that already include a guard — may be found in baby supply or medical supply stores, and online.

Getting some altitude

Bed risers (from $10 to $40 for a package of four) are plastic or wood cones that come in heights from 2 to 5 inches. They’re useful for raising the head of a bed for people with respiratory difficulties, or the entire bed to save a caregiver’s back. Short risers placed under the back legs of an easy chair shift people’s weight forward over their feet to assist in rising. They also can be used to raise the height of desks and tables to accommodate wheelchairs. Some risers come with assorted adapters and can support up to 3,000 pounds. Check local discount department stores, home improvement and hardware stores, and online.

Live from Las Vegas: Battle Against ALS Takes Center Stage

by Alyssa Quintero

For more than 40 years, Jerry Lewis has orchestrated a great American tradition — the MDA Labor Day Telethon — dedicated to bringing help and hope to people coping with progressive muscle diseases. The 21½-hour show will shine a bright light on the battle against ALS.

The 43rd Telethon — MDA’s largest annual fundraiser for its research, services and information programs — will reach some 40 million viewers nationwide and many more worldwide via streaming video on the Internet (mda.org).

MDA ALS Division Co-Chairpersons Augie and Lynne Nieto of Corona del Mar, Calif., return this year for their third consecutive appearance on the national show. Fitness pioneer and entrepreneur Augie Nieto, 50, learned he has ALS in March 2005. He and Lynne are the driving force behind Augie’s Quest, MDA’s aggressive ALS research initiative.

The Nietos work year-round raising public awareness of ALS.

Jerry Lewis with Lynne and Augie Nieto

Rounding out the show is a top-notch lineup of entertainment and celebrity co-hosts, including Telethon anchor Ed McMahon, Tom Bergeron (“Dancing with the Stars”), Jann Carl (“Entertainment Tonight”), Alison Sweeney (“Days of Our Lives” and “The Biggest Loser”), comedian Norm Crosby, and award-winning vocalists Billy Gilman and Ace Young. Also co-hosting is Nancy O’Dell (“Access Hollywood”), whose mother died of ALS earlier this year.

In addition to the national broadcast, people with ALS also will be profiled each hour on local Telethon segments, bringing home the message that ALS can strike anyone, anywhere.

The national Telethon broadcast begins at 9 p.m. EDT, Sunday, Aug. 31. To find your local Telethon station, visit www.als-mda.org, and click on “Telethon.”

Soaring to New Heights for a Cure

by Alyssa Quintero

MDA’s eighth annual Wings Over Wall Street event will be held Sept. 25 at the New York Marriott Marquis in the heart of Times Square.

Supported by celebrities and New York financial leaders, the gala raises awareness and funds to support MDA’s ALS research program, including the research teams of Hiroshi Mitsumoto, co-director of the Eleanor and Lou Gehrig MDA/ALS Research Center at Columbia University in New York City, and Jeffrey Rothstein, director of the MDA/ALS Center at Johns Hopkins University in Baltimore.

Since 2001, Wings has raised some $7 million for MDA ALS research.

Presented by sponsor RBC Capital Markets, the event will honor three outstanding leaders in the fight against ALS.

Neuroscientist Christopher E. Henderson, professor of pathology and cell biology in neurology and neuroscience at Columbia University, New York, will receive the Diamond Award, named for the event’s co-founder, Toni Diamond, who died of ALS in November 2004. Henderson also is co-director of Columbia’s Center for Motor Neuron Biology and Disease.

Philip Carlo and his wife, Laura, of New York City will receive the Spirit Award for their steadfast commitment to raising funds for ALS research and other services. Carlo, 59, received a diagnosis of ALS in October 2005. The New York Times best-selling author, known for his true crime novels, recently was featured in MDA’s ALS Awareness Month online feature “ALS: Anyone’s Life Story” (www.als-mda.org/anyone/2008series/May_2.html).

Mary McDermott-Holland of Boston will receive the Michael P. Beier Award. Named for the former Wings chairman who lost his battle with ALS in April 2003, the award honors those who motivate others to help find a cure for ALS. McDermott-Holland, senior vice president of trading at Franklin Portfolio Associates, served as a Wings event co-chair in 2005 and 2006.

For more information, visit www.wingsoverwallstreet.org; call (212) 689-9040; or e-mail specialeventwings@mdausa.org.

First Person Singular: Getting Accountability in Long Term Care

by Belinda Douglas

My mother has ALS and is a resident of a long term care (LTC) facility in Poplar Bluff, Mo. I’m a registered nurse who works in nursing homes, and yet I still can find myself struggling with the system over my mother’s care.

My mother, Amelda Dees, age 84, depends completely on others for her care. Family members make unannounced visits to her LTC facility at different times and on different days to see if her quality of care changes based on shifts or days of the week. We don’t always like what we find.

For example, when visited mid-week, my mother was found disheveled, fingernails unkempt, dirty hands and malodorous. This was not the first time she was found in such a state. Her hands have started to contract, creating a painful new situation for her. The nursing home explained that my mother refused to wear the hand splints. Their solution was to have a rehabilitation aide do daily massage to her hands. This obviously was not being done because her hands were dirty and her nails long. To make matters worse, floors in the bathroom and room also were soiled. She has started having difficulty drinking fluids, but no attempt or suggestion was made to add thickener to her liquids. MDA has provided her a communication device, but the device was in a drawer in the speech therapy room.

An attempt was made to resolve the issues with the home’s direct care staff and administration, but I felt more needed to be done. My mother deserves proper care, and to ensure her rights, her ombudsman was located online and a phone call was made. Her ombudsman called me back in a short period of time and told me the volunteer assigned to check on residents in our area was a retired registered nurse. This volunteer did respond and help. She will continue to visit my mother two to four times a month, helping ensure some accountability by the LTC facility and peace of mind for us.

Another voice for ALS care

If a care issue hasn’t been resolved even after speaking with the LTC facility (any care facility including private care homes), do not hesitate to make a phone call to the ombudsman in your area.

An ombudsman is a voice for those who cannot speak. Each ombudsman has volunteers who have been trained to go into facilities and address problems.

For example, if a resident wants to sleep in the morning but the staff makes sure the resident is at the breakfast table anyway, an ombudsman can help. Issues regarding inadequate hygiene, privacy, wound care management, pressure ulcers prevention, lack of equipment and lack of staff education regarding individual needs also are worthy of a call to your ombudsman.

Residents have the right to be restraint free, pain free, and allowed to do what they would normally do if they were in their own homes. For example, if they’d like to have a pet, or a visit from a pet, arrangements can be made to accommodate them — often creatively, depending on the pet.

People with ALS have very specific needs that must be addressed with LTC facilities, such as:

• careful range of motion exercises for comfort and mobility;
• proper toileting schedules to maintain regularity;
• communication devices that are available at all times;
• thickener for fluids when swallowing is a problem.

The list goes on, but the main point is to speak up if your particular need has not been met. After discussions/consultation with the long term care staff, are they attempting to accommodate your wishes or needs? If the answer is no, then it may be time to call the ombudsman.

Finding one

The ombudsman program operates in each state, and is funded by the U.S. Administration on Aging.

Online, the National Long Term Care Ombudsman Resource Center at www.ltcombudsman.org can direct you to your state ombudsman. By phone, call the national center at (202) 332-2275, or check local listings for your Area Agency on Aging.

Another way to find the phone number for your ombudsman is to check within the LTC facility. The facility is obligated to place the ombudsman phone number in a public area.

My advice is to not hesitate to call your ombudsman. They can be additional eyes, ears, and especially voice to the ALS patient who can no longer speak for themselves.