ALS Research: Where Are We Headed?

by Margaret Wahl

Drug trials are of great interest to the ALS community, and several are taking place at MDA’s ALS centers and clinics. Most of these result from years of laboratory experiments to determine what biochemical leads to follow and then to demonstrate a compound’s safety and expectation of benefit in cellular and animal disease models. Here are some lead compounds now being tested.

In addition to drug trials, which represent the end of the research pipeline, MDA researchers are loading the beginning of the pipeline with new ideas about biochemical pathways that lead to nerve cell death, so that more potentially therapeutic compounds can be developed. They’re on the trail of genetic and environmental factors that are different between ALS-affected and non-ALS-affected groups, while also seeking to identify factors that improve quality of life with ALS.

In the April issue of MDA/ALS Newsmagazine, we reported on a gene study of people with and without ALS by TGen (“Gene ‘Flavor’ Differences”). We’ve since learned that the study coordinator for Methodist Neurological Institute in Houston is Peggy Allred, who may be reached at (713) 441-5191 or at pallred@tmh.tmc.edu.

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ALS RESEARCH ROUNDUP

by Margaret Wahl

FDA Will Allow Ceftriaxone Study

After more than a year’s delay during which the Food and Drug Administration received additional data showing the drug was safe to give intravenously to ALS patients for several months, a trial of the antibiotic ceftriaxone is slated to begin this summer.

Ceftriaxone, used to treat neurologic infections, may have benefit in ALS by enhancing a chemical recycling process in the nervous system. It will be tested at some 40 centers, according to neurologist Merit Cudkowicz, an MDA research grantee at Massachusetts General Hospital in Boston.

Watch this publication and www.als-mda.org for more news.

NIV Improves Quality of Life, Longevity

A multiyear study of the effects of noninvasive ventilation (NIV) shows that it improves both survival and quality of life in people with moderate or no mouth and throat (bulbar) weakness, and that it improves quality of life even in those with severe bulbar weakness.

Stephen Bourke and colleagues at the University of Newcastle upon Tyne (UK) and Newcastle Hospitals Trust, who published their findings in the February issue of The Lancet Neurology, studied 22 people with ALS who were randomly assigned to standard care plus NIV, and 19 assigned to standard care alone. Quality of life was measured by a battery of questionnaires.

The NIV group survived 48 days (28 percent) longer on average than the non-NIV group.
When the results from patients with good bulbar function were segregated from the total, there was a dramatic difference, with NIV users surviving an average of 216 days (more than seven months) and non-NIV users surviving an average of 11 days.

Participants with poor bulbar function showed no survival benefit, and the investigators speculate that these patients may have been unable to use NIV effectively.

The investigators emphasize that quality-of-life measurements showed improvements for all NIV users and that, while more investigation of NIV in people with bulbar weakness should be undertaken, NIV shouldn’t be withheld from them in the meantime.

Mice With ALS Benefit From Thalidomide

M. Flint Beal

Mice with genetic ALS treated with oral thalidomide or the closely related drug lenalidomide survived slightly longer than untreated mice, report Mahmoud Kiaei at Weill Medical College of Cornell University in New York, and colleagues. MDA grantee M. Flint Beal, at the same institution, was on the study team.

Thalidomide appears to reduce levels of TNF-alpha, an inflammation-associated protein. The treated mice had less TNF-alpha in their spinal cords than did untreated mice.

Mice receiving thalidomide lived between 15 days (12 percent) and 21 days (16 percent) longer than untreated mice, and those treated with lenalidomide lived slightly longer still.

Thalidomide is available as a drug, but it causes severe birth defects if taken during pregnancy and must be used with meticulous contraception.

New Compound Boosts Glutamate Transport

Jeffrey Rothstein

A compound dubbed GPI-1046, developed with MDA support in the laboratory of Jeffrey Rothstein at Johns Hopkins University in Baltimore, shows promise in increasing removal and recycling of the central nervous system chemical glutamate by boosting production of a glutamate transporter protein.

Rothstein, who directs the MDA/ALS Center at Hopkins, and colleagues, published their findings in the February issue of Neurobiology of Disease.

GPI-1046, like ceftriaxone (see “FDA Will Allow”), improves the transport of glutamate away from nerve cells, where it can be toxic, and into surrounding cells, where it can be recycled. Mice treated with it lived 12 percent longer than an untreated group.

 

Cognitive Impairment Found in 12 of 40 With ALS

A study of 40 ALS patients conducted through the Eleanor and Lou Gehrig MDA/ALS Center at Columbia University in New York found cognitive impairment in 12 (30 percent). Of the 12, nine people (23 percent of the total) met the criteria for dementia (severe loss of intellectual functioning).

The investigators, who published their findings in the March issue of Archives of Neurology, found no correlation between cognitive deficits and the part of the body first affected by ALS, or between cognitive impairment and survival time.

In an accompanying editorial, Michael Strong, an MDA research grantee at the University of Western Ontario, notes that the cognitive changes are usually too subtle to be picked up with cursory examinations, but that understanding them fully would be helpful for patients and caregivers.

ALS With Dementia Linked to Chromosome 9

Neurologist Robert Brown, who heads the MDA/ALS Center at Massachusetts General Hospital in Boston, was among the investigators who studied a 50-member Scandinavian family in which five people carried a diagnosis of ALS and nine a diagnosis of frontotemporal dementia (FTD), a disorder characterized by behavioral disturbance and personality change.

Although there were no family members who had ALS and FTD, the researchers, who published their findings online Jan. 18 in Neurology, say they think a single cause, arising from a gene on chromosome 9, probably underlies both conditions, with additional factors determining whether the result is ALS or FTD.

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MDA ALS Division —

Research, Services, Information

The Muscular Dystrophy Association’s ALS Division assists people with Lou Gehrig’s disease and their families through the most comprehensive program of any voluntary health agency in the country. Research to uncover cures and better treatments; services, including medical care; and information needed to manage daily life with ALS are the elements of MDA’s program of assistance.

This year MDA is spending $17 million on its ALS program. For more than 50 years, MDA has led the world in ALS research and services, investing nearly $190 million.

RESEARCH

MDA’s ALS Division funds top researchers worldwide seeking causes of, and treatments and cures for, ALS. MDA supports projects ranging from basic microbiological research on the causes of the disease to clinical trials of potential treatments. Information about participating in a clinical trial can be found at www.mda.org/research/ctrials.aspx or in “Research Roundup” in this newsmagazine.

MEDICAL CARE

A doctor who suspects someone has ALS can refer the person to a local MDA office to make an appointment at one of MDA’s 240 hospital-affiliated clinics or 36 designated MDA/ALS centers. There, a multidisciplinary team of experts will conduct a diagnostic examination. People who have ALS and who register with MDA can receive follow-up care by health care professionals, throughout the course of the disease.

OTHER SERVICES

Through its local offices, MDA offers support groups for those with ALS and their caregivers.
People with ALS can borrow devices to help with day-to-day living from MDA’s equipment loan closets. MDA also assists with the cost of wheelchairs, leg braces and communication devices, as well as wheelchair repair.

To find your nearest local MDA office, go to www.mda.org.

INFORMATION

MDA is the nation’s best source of news about ALS research developments. Its publications also provide thorough information on coping with medical, financial, practical, emotional, and other challenges presented by the disease.

The starting point for this information is MDA’s ALS Web site, at www.als-mda.org, or your local MDA office.

At the Web site, in addition to news, you’ll find regular chats for those dealing with ALS and for their caregivers.

To sign up for chats, go to www.mda.org/chat/chatroomlogin.aspx. You can see transcripts of past chats at www.mda.org/chat/transcripts.html.

PUBLICATIONS

Several ALS-specific publications are available at your local MDA office or from MDA National Headquarters. Many of these MDA publications also can be found on the MDA/ALS Web site.

Everyday Life With ALS: A Practical Guide: A 150-page illustrated book providing basic information on saving energy, home modification, respiratory and speech equipment, mobility equipment, exercise and more.

Facts About Amyotrophic Lateral Sclerosis: An introductory pamphlet for those with new diagnoses.

Los Hechos Acerca de la Esclerosis Lateral Amiotrófica: The Spanish translation of “Facts About ALS.”

MDA/ALS Newsmagazine: A monthly publication featuring news on ALS research, profiles of people with ALS, and insightful articles on health care and caregiving.

Meals for Easy Swallowing: A book of recipes and feeding tips. No longer in print, but available online.

Quest: MDA’s bimonthly national newsmagazine, reporting on many issues of living with neuromuscular diseases and on helpful products.

When a Loved One Has ALS: A Caregiver’s Guide: A comprehensive manual filled with practical advice.

VIDEOS

Videos available from local MDA offices offer helpful guidance on setting up an ALS support group; ventilation options; and ALS research findings.

Breathe Easy: A Respiratory Guide for People Living With Neuromuscular Diseases: This educational video explores options for assisted breathing devices and techniques.

Breath of Life: This version of “Breathe Easy” is geared for use by physicians and other medical professionals.

Support Groups: The MDA Support Group and You; Your MDA/ALS Support Group: Getting Started; and ALS: Maintaining a Positive Perspective: These three videos may interest new and ongoing support groups.

With Strength and Courage — Understanding and Living With ALS: This video provides an introduction to ALS by Dr. Stanley Appel, a leading ALS researcher and director of the MDA/ALS Center at the Methodist Hospital in Houston. It’s available on loan from your local MDA office.

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The Private Battle of Robert Borsellino

by Stephen M. Delgado

One can hardly watch a newscast without hearing about some battle being fought in some part of the world, but there’s also another kind of battle being fought by more than 30,000 Americans who have ALS.

A journalist in Des Moines, Iowa, is engaged in such a battle. Meet Robert Borsellino, a columnist for the Des Moines Register. Although his body has been weakened by the disease, his pen still has the might of a howitzer.

Borsellino grew up in a tough Bronx, N.Y., neighborhood in the 1950s and 60s. He graduated from Bronx Community College and the State University of New York at New Paltz.

Borsellino, 56, is married to Rekha Basu, who is also a columnist for the Des Moines Register. They have two sons, Raj, 19, and Romen, 16.

Borsellino has a resume rich in newspaper background, peppered with some years in radio and television. His newspaper experience includes stints with Newsday, the Albany Times Union, the Kingston Daily Freeman, the South Florida Sun-Sentinel and the Des Moines Register.

The Register hired Borsellino in 1994 as the metro editor, and he became a columnist in 1998. He’s written scores of articles about everything from homeless youth to his meeting with Ronald Reagan.

No matter what or whom he writes about, his common denominator is putting a human face on his subject and taking the reader inside the person. Borsellino is currently working part-time for the Register.

Declaration of War

In the autumn of 2004, Borsellino’s world completely changed, when a dreaded disease declared war on his body. A few months later an article he wrote would become profoundly personal. He’d take the reader inside Rob Borsellino.

The article was titled, “I Can Kick the Denial, Not the Disease.” It ran in the Des Moines Register Feb. 23, 2005, and is one of the collection of articles penned by Borsellino in his recent book So I’m Talking to This Guy… (Des Moines Register).

“I was slurring my words; I was tired, and I felt weak,” Borsellino wrote. “Finally, I went to see a doctor,” he recalled. “But, the doctor ran some tests and was spooked by what he saw. He sent me to a second doctor — a nerve specialist.

“That guy ran more tests and at the end of the session, he’s telling me I have some fatal, incurable, exotic-sounding disease called amyotrophic lateral sclerosis (ALS), also called Lou Gehrig’s disease. Then he told me that most people only live a few years with this disease.”

What’s more, Borsellino recounts seeing several other doctors around the country and being told the same thing. He said that each time he heard it, he was in denial. The recurring thoughts that he wouldn’t be there for his sons’ weddings, and that he wouldn’t see his grandchildren, kept haunting him.

Fighting Back

Twelve-step programs such as Alcoholics Anonymous stress to their members the idea of living “one day at a time.” When a person’s future is in a precarious position because of a disease, one day at a time may be the best way to cope.

If a good attitude is vital in coping with a catastrophic disease, Borsellino has one. He isn’t going to quit or do a gloomy Gus act. His tough upbringing tempered his psyche.

“It has been tough, but my attitude is to keep having fun as long as we can.”

Borsellino is still walking, but not talking. He is attending MDA clinic, is receiving assistance from the MDA loan closet, and a network of friends helps every day with various tasks, such as “helping me to dress and make breakfast. My son, Raj, has taken the semester off from college to be at home to help me, too.”

In all, Borsellino’s gift of empathy is matched by his sense of humor. In light of what he’s going through, he found something to smile about and to bring a smile to us when he was trying to think of a positive angle.

“I’m toying with the name. At least it’s called Lou Gehrig’s disease and not Steinbrenner Syndrome or Dizzy Dean Disorder.”

For a Yankee fan who grew up in the Bronx, it’s an ironic connection to one of the greatest Yankee players ever.

Rob Borsellino has agreed to contribute an article to a future issue of the MDA/ALS Newsmagazine. Borsellino has been named the recipient MDA’s 2006 Personal Achievement Award for Iowa.

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