ALS RESEARCH ROUNDUP

by Margaret Wahl

Embryonic Stem Cells Can Become Motor Neurons

Researchers at the University of Wisconsin-Madison announced online on Jan. 30, in Nature Biotechnology, that they’ve developed a chemical recipe to coax human embryonic stem cells to develop into motor neurons, the muscle-controlling nerve cells that are lost in ALS.

Xue-Jun Li and colleagues used two federally approved lines of stem cells and exposed them to retinoic acid early and to several other compounds later on.

Vassilis Koliatsos, an MDA-supported neuropathologist studying stem cells at Johns Hopkins University in Baltimore, says the Wisconsin researchers’ recipe works well in laboratory containers, but that putting them into animals will likely “hold many surprises.”

Koliatsos said it’s unclear whether the new motor neurons would survive in the face of an overwhelming degenerative process like that seen in ALS. And, he notes, even if they did survive, getting them to “talk to” muscle cells is another unmet challenge.

In ALS and other neurodegenerative diseases, Koliatsos says, every neuron lost increases the chance that more neurons will be lost. “It’s theoretically possible that we can put in the right number of cells such that the neurodegenerative process can be delayed significantly,” Koliatsos said, adding that not much else can yet be predicted.

Vitamin E, Military Service May Affect ALS Risk

Data collected from nearly a million people who participated in a questionnaire-based study beginning in 1982 and ending in 1998 have been used to determine what, if any, links exist between diet and other lifestyle factors and causes of death.

When the data were analyzed with respect to ALS, investigators found that taking vitamin E supplements may help prevent the disease, and that service in the military may add to the risk of developing it.

Those who reported taking vitamin E supplements for at least 15 days a month for 10 years or longer had 38 percent as great a chance of developing ALS as those who never used vitamin E. For those taking vitamin E for fewer than 10 years, the risk was 59 percent of the risk for non-vitamin E users.

Albert Ascherio, an associate professor at the Harvard School of Public Health and an author on both studies, cautions that no one should use vitamin E on the basis of these results, which need confirmation. The vitamin E study is in the January Annals of Neurology.

Data on military service were collected on approximately 400,000 men who filled out the questionnaire. All military service took place before the Gulf War. Of the 280 ALS-related deaths recorded, 217 were among the 281,874 men who had served in the military, implying an ALS death rate of about 0.08 percent among the ex-military; and 63 were among the 126,414 who had never served, making an ALS death rate of about 0.05 percent in that group.

Men who had served in the military had an ALS-related death rate that was 1.53 times the rate for men who had never served.

In their Jan. 11 paper in Neurology, the authors say the results suggest that exposures associated with military service but not unique to the Gulf War should be investigated.

ALS Epidemiology Study Under Way

Hiroshi Mitsumoto

An MDA-funded study of ALS “epidemiology” (disease patterns) is under way at Columbia University Medical Center in New York, headed by Hiroshi Mitsumoto, co-director of the MDA/ALS Center at that institution.

The study will use interviews, questionnaires and blood samples to investigate what, if any, relationship exists among factors in a person’s residential, employment, medical, military and lifestyle history; his or her DNA; and the development of ALS.

The researchers prefer residents of the New York area, at least for the present. The study is scheduled to remain open until January 2007.

For more information, contact Ani Sara Thankachan in New York at (212) 305-4746.

Minocycline Trial Seeks Participants

There are openings for participants in a large, multicenter trial of minocycline, an antibiotic in the tetracycline family, in ALS. Minocycline appears to have anti-inflammatory and neuroprotective properties and penetrates the central nervous system.

At sites across the United States, minocycline is being tested against a placebo (inert substance) in 400 adults with ALS who have fairly good respiratory function. Patients taking riluzole can participate if the riluzole dose is stable.

For more information, contact Carolyn Doorish, project coordinator, at (212) 305-2027 or cd2141@columbia.edu; and see the clinical trials database at www.mda.org/research/ctrials.aspx.

New CoQ10 Study Opens in 19 Centers

A trial of high doses of coenzyme Q10 (coQ10) in 185 people with ALS is now open for recruitment across the United States. Investigators will compare coQ10 with a placebo (inactive substance) to see whether it slows the course of the disease.

CoQ10 is a natural compound that acts inside the mitochondria, the “powerhouses” of the cell. It supports the cell’s energy metabolism and helps to neutralize free radicals, molecules that carry an electrical charge and can damage other cellular components.

The compound has been found to be safe and relatively well tolerated in people with ALS, even when taken at high doses.

Adults with ALS who aren’t ventilator-dependent or who use part-time noninvasive ventilation, have had ALS for less than five years, and who meet other study criteria, are eligible.

For information, contact Alexandra Barsdorf, clinical coordinator, at Columbia University Medical Center in New York, at (212) 342-3026 or aib2104@columbia.edu; and see the clinical trials database at www.mda.org/research/ctrials.aspx.

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Travel Tips From People on the Go

by Kathy Wechsler

Retired nurse Jan Sluiter, of Cedar Falls, Iowa, received a diagnosis of ALS in 1988 and uses a power wheelchair. Sluiter, 55, and her husband, Jim, travel twice a year by van to Ontario, Canada, to see family. They’ve also flown to the Bahamas, Hawaii, Arizona, Florida and Washington and don’t plan to slow down.

Jan and Jim Sluiter enjoy Hanauma Bay on the island of Oahu, Hawaii, in November 2003. Jan Sluiter relaxes in a rented beach wheelchair.

Here’s some advice from Sluiter that’s helped make her travels more enjoyable:

• Always travel with your living will, for emergencies.
  
• Never book flights online or through a travel agency. Sluiter reserves through the airline’s headquarters (usually Northwest Airlines) to ensure they understand her needs. Before the flight, she calls the airline to confirm she’s coming.
  
• Choose flights that use jetways to avoid steps to the airplane. If there won’t be a jetway, Sluiter ensures there will be a forklift with a platform and a forklift operator to raise her in the chair up to the plane door.
  
• Arrange for an aisle seat near the front. If Sluiter can’t get a seat toward the front, airline employees are trained to take her down the aisle in a straightback wheelchair or aisle chair.
  
• Never take your power chair when traveling by air, to avoid damaging it. Sluiter checks her manual wheelchair at the gate instead of curbside or sending it through with the luggage. Somebody will bring her chair right to the front of the plane when it’s time to exit the aircraft.
  
• Allow at least an hour between connecting flights for gate changes. Wheelchair users are the last passengers off the plane.
  
• Call ahead to the rental car company to make sure the shuttle is wheelchair accessible. (Hertz has accessible shuttles.)
  
• Always reserve the hotel room in advance. Sluiter specifies her exact requirements. Of course, the bathroom has to be large enough and have a raised toilet seat and grab bars, but she also spells out that she wants a roll-in shower. She’s been happy with the Sheraton, Marriott, Holiday Inn Express, AmeriHost, AmericInn and Homestead Suites. Before leaving home, she calls again to double-check that her needs will be met.

Steve and Helene Nichols of Clifton, Va., drive all over the East Coast, and they’ve cruised Alaska, Bermuda, Russia, some Caribbean islands, the Panama Canal and the Hudson River. A retired computer network specialist, Steve, 54, has had ALS for 10 years and uses a power chair that he operates with a knee switch. He also has a tracheostomy and a feeding tube and uses a communication system to speak. Steve’s the 2005 MDA Personal Achievement Award recipient for the state of Virginia.

Steve and Helene Nichols set sail for Bermuda from New York City in August 2004.

Here are some helpful travel tips from Steve and Helene:

• Organization’s the key. Helene makes supply lists for all equipment needed for Steve’s care. The lists include everything from portable lifts to Steve’s eye-tracking communication device.
  
• Once the Nicholses are on a ship, all their supplies are easily available. There’s no need to haul them around because the hotel travels with them.
  
• Do your homework. The couple ask for specific accommodations such as a roll-in shower. Larger ships, they say, tend to be more accessible, with larger cabins and larger bathrooms, wheelchair-accessible entertainment and medical facilities. Steve and Helene ensure the ship docks in a port because transport boats to the ship are generally too small for the power chair. They’ve found Holland America and Royal Caribbean to be very accessible.
  
• Call ahead and make sure that there are vans with wheelchair tie-downs for any land travel.
  
• Don’t go on trips in the winter because of the risk of exposure to the flu.
  
• Get some help. A friend often travels with them, so that if Helene wants to do her own thing, their friend makes sure Steve is safe.
  
• When traveling in the United States, always carry the phone number of your MDA clinic doctor. When driving, the Nicholses carry a list of dealers that can help with their accessible van.
  
• Carry travel insurance at all times. The Nicholses are always prepared to evacuate the ship by medical transport and know ahead of time how to get off the ship in a medical emergency; travel insurance would help pay for it. The couple also carries extra health insurance forms.
  
• Don’t put it off. The Nicholses wish that they’d flown to Australia and other faraway destinations while Steve had greater mobility. They advise you to go to the distant places before your needs expand.

You can e-mail Jan Sluiter at jjsluiter@cfu.net and Steve and Helene Nichols at slohcinjs@hotmail.com. For more information on airport security, see “Leaving on a Jet Plane…,” in MDA’s magazine Quest, March/April 2003. To find out more about airplane travel in general, see “How to Fly Through the Air With the Greatest of Ease,” in Quest, April 2000. Quest’s regular column “To Boldly Go” explores accessible travel destinations.

Face-off Draws Fire I enjoyed reading the two opposing positions on the multidrug trials (“Face-off on Multidrug Trials,” January) and felt compelled to address a few of the comments made by Jeremy Shefner (director of the MDA/ALS center in Syracuse, N.Y.). I submit that a clinical trial that conforms with medically and scientifically accepted practices has merit. Even if the trial fails, it provides data to expand the knowledge base for understanding motor neuron diseases. “Patients want to know what works” as an argument to diminish the value of the trials is not valid. I would be delighted to take a concoction if it meant I could walk again. Alternatively, “you don’t just combine them” is correct unless the experimenter has a valid hypothesis for selecting the components. Each ingredient has a perfectly good reason for inclusion in the “cocktail.” Indeed, Jeffrey Rosenfeld (director of the MDA/ALS center in Charolette, N.C.) states his purpose is to determine the safety and feasibility of simply taking the pills and not the efficacy. I would much prefer Shefner to offer constructive criticism that would strengthen the trials instead of dismissing them out of hand. Finally, I am grateful that Dr. Rosenfeld is being proactive and treating the symptoms of motor neuron disease. The alternative is a life without hope. Angelo Sciulli Lancaster, S.C.

Denise Figlewicz, Ph.D.: Turning the ALS Kaleidoscope

by Margaret Wahl

Denise Figlewicz, an associate professor and research scientist in the Department of Neurology at the University of Michigan, says she’s wanted to be in science ever since she was a child, growing up in Chicago. One of four children, and an identical twin, Figlewicz learned the chemical formulas for things like water and sugar from her pharmacist mother, who taught her that “chemistry was just a language.” She learned about astronomy, geology and biology from her engineer father, who frequently told his children, “Open your peepers and look at the world.”

Denise and her twin sister Dianne, now a neuroscientist at the Veterans Affairs Medical Center and University of Washington in Seattle, graduated from high school at 15 and entered Loyola University, from which they both graduated at 19.

Neuroscientist Denise Figlewicz

Denise went on to complete her doctoral degree in biochemistry at Loyola and then to study at the National Institutes of Health and National Naval Medical Research Institute, both in Bethesda, Md.

Opportunity Knocks

In 1984, Figlewicz was a young biochemist at Harvard, studying myelination, the process by which an insulating sheath is wrapped around nerve fibers.

There, she met neurologist Robert Brown, who told her of an opportunity in Switzerland involving the study of motor neurons, the nerve cells in the spinal cord and brain that control muscle activity and that are mysteriously lost in ALS.

Denise Figlewicz and her twin sister, neuroscientist Diane Figlewicz Lattemann. "You wouldn't believe how many things are programmed genetically," Denise says.

“I thought, ‘This is a chance to go live in Europe,’” Figlewicz remembers. “No one will offer this again.” It meant adjusting her goals a little, but it was still neuroscience, and it intrigued her. “So I switched to motor neuron diseases,” she says, “and I’ve stayed in that field ever since.”

Once in Lausanne, Figlewicz began tackling the wobbler mouse, a model of motor neuron disease commonly used in the 1980s. Figlewicz’s role was to compare the proteins in spinal cords of the wobbler mice with proteins from non-wobbler spinal cords. It was rough going.

“These mice went downhill very quickly,” she says. “By the time you noticed the symptoms and took the spinal cord out for study, the motor neurons were gone. I thought, ‘I’m wasting my time. This mouse has a mutant gene that’s causing this trait. If we could find the gene, we’d have the answer.’”

But molecular genetics was a young science, opportunities to study mouse genes were scarce, and in 1987, Figlewicz returned home to Harvard.

A Payoff

The timing was fortuitous. Brown was getting together with other investigators to form what would later be known as the Familial ALS Consortium, to identify an ALS-causing gene in patients.

Teepu Siddique and Allen Roses, both then at Duke University, and Guy Rouleau at Montreal General Hospital, were part of the new, MDA-supported project. “MDA paid for us to meet once or twice a year and talk about our work,” Figlewicz recalls. “Everybody else said this was a long shot, but MDA said, ‘If you get together and share your results, we’ll fund you.’”

Mutations in the SOD1 (superoxide dismutase 1) gene were already under suspicion, because in some of the families in which the disease appeared to be inherited (familial), all the affected members had unusual DNA sequences in the same area of chromosome 21 — SOD1’s neighborhood.

The long shot paid off. In 1993, the FALS Consortium scientists published a paper showing unequivocally that mutations in the SOD1 gene could cause a familial form of ALS.

The following year, MDA grantee Mark Gurney at Northwestern University developed an animal model of ALS by breeding mice with an SOD1 mutation known as G93A, a model used by the majority of ALS researchers today.

Beyond SOD1

But Figlewicz speculated that, even in those few families where the disease was clearly caused by mutated SOD1, there had to be other factors involved.

“In a given family where the mutation turned out to be SOD1, we still saw tremendous variation in the age of onset and in the nature and course of the disease. You could have two closely related people with the exact same mutation, and the clinical phenotype [observable traits] could be different.”

Figlewicz thought about differences in environmental exposures, and still does. But she also felt certain there were differences in genes besides SOD1 that modified the illness. Finding them might, she reasoned, allow for more accurate predictions of risk in ALS patients’ relatives. Moreover, it could open the door to understanding more biochemical factors that can enhance or minimize the death of motor neurons.

Figlewicz’s group has MDA funding to test the effects of the G93A mutation in SOD1 in up to six strains of mice and has started with three.

So far, she’s found that the severity of the SOD1-caused ALS is “very different” depending on the mouse genetic background (strain), even when the mice live in the same environment.

“You wouldn’t believe how many things are programmed genetically,” she says, joking that she’s a “genetic clone” herself and relating tales of how she and Dianne not only have pursued similar careers, but share the same preferences in art, music, movies and nail polish, and buy people the same Christmas presents.

“Science is like a kaleidoscope,” she says. “There are facts and studies that you’ve looked at and made a mental note of, and then you turn the kaleidoscope a little and you see a new picture emerge.”

ALS Online Meals for Easy Swallowing, no longer in print, is now available in its entirety on the MDA Web site. The 125-page book comprises a collection of recipes for foods for people who have swallowing difficulties. The easy-access, online version provides recipes for meats and other protein-containing foods, fruits or fruit drinks, vegetables, and breads, as well as suggestions on food preparation and service. Selections of beverages, desserts and sauces also are provided. The online guide also contains swallowing tips and techniques. The book was published by the MDA/ALS center at Baylor College of Medicine in Houston.

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A Qualified Income Trust: Keep Your Medicaid Eligibility

by Kathy Weschler

One of the principal responsibilities of Medicaid is to pay for nursing home care for those who qualify for this federal health care assistance program.

If you’re going into a nursing home and your state disqualifies you from receiving benefits because your income exceeds the Medicaid limit, you may feel as if you’re swimming against a strong current: You can’t qualify for nursing home Medicaid benefits because your monthly income exceeds the income cap, but you don’t receive enough monthly income to pay for your nursing home without help from Medicaid. What to do?

Used in states that have income caps on those who qualify for Medicaid benefits for institutionalized care, the Qualified Income Trust (QIT, also known as a Miller Trust) is a legal way around the income limit, says K. Gabriel Heiser, an elder-law attorney in Boulder, Colo.

WHAT’S A QIT?

A QIT is an account in which you deposit enough of your income — earned, pension, Social Security, etc. — to reduce your qualifying income for Medicaid coverage of your nursing home care. In most states, the income cap is $1,737 per month, or three times the current Supplemental Security Income [SSI] benefit.

Placing funds into a QIT lets you qualify for Medicaid eligibility for benefits such as long-term care programs, according to a Florida Department of Children & Families (FDCF) official. For other restrictions on the QIT, see “Medicaid and Your Money.”

When creating a QIT, make sure you’re dealing with someone experienced in the Medicaid arena, such as an elder-law attorney who’s familiar with QIT accounts and how they work, advises Charles Robinson, an elder-law attorney in Clearwater, Fla. To find such an expert in your area, visit the National Academy of Elder Law Attorneys Web site at www.naela.org.

Both Heiser and Robinson recommend appointing a QIT trustee; one isn’t required but is helpful.

It’s important to note that you don’t set up a QIT in advance, but rather in the first month that you’re in the nursing home and seeking Medicaid benefits, Heiser says. Your attorney will help you set up a special bank account (usually a checking account) to be used specifically for the QIT.

The account then pays you a monthly personal needs allowance (which varies from state to state; e.g., it’s $35 in Florida and $50 in Colorado).

If you’re married, the QIT may also pay your spouse living at home an income allowance, if his or her income doesn’t meet your state’s allowance level.

The amount remaining in the QIT after the two allowances are paid, along with your Medicaid qualifying income, is paid to the nursing home. Medicaid then covers the difference between what you’ve paid and the nursing home’s actual charges. The QIT’s resources and your income will then be entirely exhausted.

When you die, the state receives all money remaining in the trust up to the amount that Medicaid has paid on your behalf.

QIT Example:
$ 1,900	monthly income	$ 6,000	nursing home cost
$-1,737	income cap	$-1,737	paid by client
$ 163	to QIT	$ 4,263
$ -50	personal needs allowance	$ - 113	paid by QIT
$ 113		$ 4,150	paid by Medicaid

A SIMPLE EXAMPLE

“Bob,” who’s 41 and lives in Colorado, received a diagnosis of ALS three years ago and is now looking for a good long-term care facility in the area.

Bob’s assets are below $2,000, but he isn’t eligible to receive Medicaid benefits because his monthly income, from Social Security benefits and his pension, is $1,900, which is $163 over the income limit of $1,737. Without help from Medicaid, there’s no way he can pay the $6,000 monthly bill from the nursing home.

That’s where the QIT comes in. Because he wants his Medicaid benefits to start in February when he moves into the facility, Bob and his sister Sue visit Richard Jones, a local elder-law attorney in February. Sue is named Bob’s trustee, and Jones establishes a separate bank account in her name for the QIT.

Each month, Bob’s excess income ($163) is transferred to the QIT, and Bob pays the nursing home $1,737. Then, Bob’s monthly personal needs allowance of $50 is paid out of the QIT by Sue. Sue then pays the nursing home the remaining $113 and the trust balance goes to zero. Medicaid pays the facility the balance of $4,150.

QIT BENEFITS OUTSIDE A NURSING HOME

Can you use a QIT to qualify for Medicaid benefits if you’re not going into a nursing home? The answer varies from state to state.

Some states, such as Florida, have nursing home diversion Medicaid waiver programs, which allow for care at home. Depending on the state, Medicaid might pay for an assisted living facility. To use a QIT, you need to be going into a long-term care program, not just looking for Medicaid assistance with prescriptions or physician visits.

The contents of this article are intended to be general information and shouldn’t be construed as legal, tax or financial advice.

Medicaid and Your Money Medicaid is a federal program, but it’s administered by the individual states. That means the guidelines and regulations on QIT and other Medicaid programs vary from state to state. To find out whether you’re eligible for Medicaid assistance, check with the Medicaid office in your state. Each state establishes its own eligibility requirements based on three criteria: your care needs, your income and your assets. Earned wages, Social Security, disability insurance, retirement, pension and alimony all count toward the income cap for Medicaid eligibility. There’s also an asset limit imposed on Medicaid recipients: $2,000 for an individual seeking institutional care and $3,000 if both spouses need institutional care. Assets consist of bank accounts, brokerage accounts, stocks and bonds, loans, annuities, and any resource of value owned jointly by you and your spouse. In most states you’re allowed to retain one home and one vehicle outside the asset limit, but things like your boat and your private airplane count against you. Once you’re eligible for Medicaid, most states also cover physician, psychologist, rehabilitation, chiropractic, dental, laboratory and X-ray services, hospital visits, prescription drugs and prosthetic devices. To learn the rules of your state’s Medicaid program, visit www.cms.hhs.gov/medicaid/statemap.asp, and click on your state; and call your Medicaid agency. You also can call Centers for Medicare & Medicaid Services at (877) 267-2323.

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