FIRST PERSON SINGULAR
Talking To Your Kids About ALS

by Aimee Chamernik

As we huddle on the couch, munching popcorn and engrossed in our movie, the kids and I are startled by a sharp knock at the door. Before I can shift forward to start the painstaking process of standing up, our neighbors burst into our house.

“Are you OK?!” Beth asks breathlessly.

“Yes, we’re fine,” I answer sheepishly, as it dawns on me that I never called my husband back after Nick left a message for him telling him I’d fallen. I’d been so preoccupied with reassuring Nick (9), Emily (7) and Zachary (3) that I was OK — and responding to Zachary’s persistent demands for popcorn — I’d forgotten to follow up on Nick’s frantic call. “I’m so sorry!”

“Oh, we’re just glad you’re OK!” they say in unison. “Jim called because your phone is off the hook, and he was worried.”

I dig the phone out of the couch cushions and click “end.”

“Oops! No, we’re fine. I’ll call Jim right away.”

The kids, at first too stunned to speak, start spouting a hundred questions at once.

“What are you doing here?” “Did you think our mom was hurt?” “How did you know she fell?”

After a few moments of small talk — apologies and profuse thanks on my side, gracious reassurances on theirs — they pull the door shut behind them.

“Well,” I say, turning to the kids, “I feel terrible that we made everyone worry, but that was kind of good practice for an emergency.”

“Like a tornado drill at school,” Emily nods.

“At least we know we can count on our neighbors for help!” Nick pipes up.

And those words make this embarrassing incident worthwhile. I’m glad he feels reassured.

Since ALS has invaded our lives, the toughest challenge has been embroiling our innocent children in this losing battle. While we were tempted to try to shield them from ALS for as long as possible, we’ve ended up taking the opposite approach.

After two-plus years, do we have all the answers? Hardly. But we‘re finding that a straightforward approach helps to draw our family closer together through this experience.
Here are some of the tenets we try to live by:

Be Honest

We talk honestly about ALS with our kids, answering questions in an age-appropriate way. We’ve promised that we will always tell them the truth, and if we don’t know an answer we will try to find one.

Our conversations have ranged from matter-of-fact to heart-wrenching, but the unifying characteristic is that after all of them the kids feel better. By discussing their questions or fears openly, we can help them deal with their feelings.

Don’t Dwell on ALS

As my balance and coordination began to fail, we slipped into the habit of telling the kids to pick up their toys “or Mom could fall.” We quickly realized that we were wrongly shifting the focus to ALS. If ALS weren’t part of our lives, we would still teach our children to pick up their toys.

While ALS is unavoidable at times, we try to steer clear of needlessly emphasizing the disease that already commands so much attention.

Keep Persevering

You know how kids have that uncanny knack for never hearing “please put your dirty clothes in the hamper” but always hearing what you’d hoped slipped past them? In the back of my mind is the knowledge that my children are watching and learning from me every moment of every day.

I try to let that knowledge guide my behavior on the days when I want to hide under the covers and never come out. Is that how I want them to remember me dealing with adversity? Or how I want them to face adversity in their lives?

No, I want to teach them to dig deep and find the inner strength to live each moment to the fullest. And I don’t hesitate to talk about that choice.

“This is one of those times when I just want to give up,” I’ll say. “But I will not let ALS win!”

Let the Kids Help

This one’s tough. I’m struck by how topsy-turvy our lives have become; my kids now tie my shoes instead of having me tie theirs. I struggle with becoming a burden, but they are happy to help. Whether they are fetching things I’ve dropped, carrying my purse, or shielding me in public places, they’re glad to be my arms and legs.

“When I keep people from bumping into you, I feel like your knight in shining armor!” Emily grins proudly.

Furthermore, they’re learning patience, kindness, and sensitivity to the needs of others. This isn’t how anyone would choose to instill those traits, but I can’t help but be grateful for that positive.

Take Control Where We Can

Jim and I often lament our lack of control, with ALS constantly lurking and snatching more from our family. We can only imagine how much stronger that feeling is for the kids.

One way we can take back a measure of control is by trying to make a difference in the fight against ALS. The kids are eager to join fund-raising efforts, participate in events to raise awareness, and write or draw about their experiences with ALS.

We also establish some control by staying a few steps ahead of my disease. Whether we’re installing grab bars, removing household hazards, or enlisting neighbors to check on me, we keep the kids involved in our safety measures and plans.

When our neighbors burst in on us that night, the kids talked about it for weeks. They are comforted by the fact we have people who care about us and are ready to help out at a moment’s notice.

And while we’d rather shield the kids from ALS entirely, we all find comfort in facing it together.

Amy Chamernik received a diagnosis of ALS in 2004.

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by Margaret Wahl

NIH Group Finds No Clear DNA Clues to ALS

No significant genetic differences were found in a recent study of 276 people with sporadic (nonfamilial) ALS and 271 without the disease, says a report issued in February by a large group of U.S., British and Italian researchers.

Jennifer Schymick at the Neurogenetics Laboratory of the National Institutes of Health (NIH) in Bethesda, Md., and colleagues, who published their findings online Feb. 20 in Lancet Neurology, initially identified 34 DNA differences in their ALS- affected versus unaffected blood samples, all of which came from white, non-Hispanic U.S. residents with no family history of ALS. The study was funded by NIH, the Packard Center at Johns Hopkins University in Baltimore, and private organizations.

Among the identified differences were several in genes associated with the cytoskeleton, which is the scaffolding of cells, and genes that influence transport of compounds inside nerve fibers.

The investigators feared, however, that they might have identified “false positives,” meaning differences that appeared to be significant between the two groups actually weren’t. They therefore applied an extremely conservative mathematical procedure to their data analysis, after which none of the differences reached significance.

The MDA-supported Translational Genomics Research Institute (TGen) in Phoenix announced in November at an international ALS meeting in Yokohama, Japan, that it had identified significant genetic differences in the DNA of ALS-affected compared to unaffected study participants. (See “Genome-Wide Search Hits Pay Dirt,” January.) The TGEN group expects to publish a paper in the near future.

That study, which compared the genomes (all genes) of 1,200 people with and 2,000 people without sporadic ALS, identified some 50 genetic differences in the two groups. Several are related to so-called adhesion proteins, which form molecular glue that holds cells in place.

“I think the two studies can’t be directly compared at this point,” said Sharon Hesterlee, MDA Vice President of Translational Research. “The TGen study, which has not yet been published, used somewhat different statistical methods and larger sample sizes. Ultimately, both studies will probably need to be confirmed independently before hard and fast conclusions can be drawn.”

Do Neurons Have a Unique Stress Response?

Heather Durham

Motor neurons, the nerve cells that die in ALS, as well as other neurons, seem to have a particularly high threshold for activating a stress response that non-neuronal cells activate more easily, according to findings from the laboratory of MDA grantee Heather Durham at Montreal Neurological Institute at McGill University. That problem, if it could be remedied, might become a therapeutic avenue in ALS, the researchers say.

Building on work in the Durham lab and by Ian Brown at the University of Toronto at Scarborough, graduate student David Taylor and colleagues set out to decipher why the usual pathways for turning on protective stress responses are difficult to activate in motor neurons, whether or not they’re affected by ALS.

They found that neuronal cells don’t start production of protective compounds called heat shock proteins in response to the usual signals that activate these proteins in other cells.

The team, which published its findings in the January issue of Molecular and Cellular Neuroscience, identified a new pathway for turning on heat shock protein production in neurons, one that didn’t trigger this response in non-neuronal cells.

“These are clues pointing to alternative mechanisms of activating stress responses in neurons compared to other cells, and we’re continuing to try to identify these pathways,” Durham said.

Canadian Group Makes Nerve Cells From Skin

Francois Berthod at Laval University in Quebec City and colleagues say they’ve isolated cells that can become mature human neurons (nerve cells) from human skin cells, with implications for both research and treatment.

The investigators, who published their findings in the February issue of the Journal of Cellular Physiology, say they obtained skin cells from patients who had undergone breast reduction surgeries, grew them in plastic lab dishes in an environment that favors neuron development, and monitored them for seven weeks.

During that time, the cells went through the normal nerve cell developmental stages, producing proteins characteristic of each stage. They also began to form connections with each other, as nerve cells normally do.

In the near term, Berthod notes, the ability to produce human neurons from human skin cells could have a positive impact on research, because the inability of mature human neurons to divide makes these cells a scarce resource and forces most investigators to use animal nerve cells.

In the long term, Berthod says, it’s possible that replacement neurons could be produced from a patient’s own skin, thus eliminating the problem of rejection by the immune system.

“We are now trying to push the differentiation [maturation] of these neurons into a motor neuron fate,” says Berthod, who has MDA support for ALS research. (Motor neurons are the cells affected in ALS.) “That would be of great interest for the study of motor neuron diseases.”

Avanir Meets With FDA on Zenvia

Avanir Pharmaceuticals (www.avanir.com) of Aliso Viejo, Calif., announced on Feb. 28 that it has met with the U.S. Food and Drug Administration to respond to the agency’s concerns about Zenvia (formerly called Neurodex), the company’s product for “involuntary emotional expression disorder” (IEED, also known as pseudobulbar affect).

Zenvia is a combination of quinidine and dextromethorphan and was developed to help patients regain control of unwanted episodes of laughing or crying that can occur in some neurological disorders, including ALS. In October, the FDA raised concerns about the safety of Zenvia and declined to approve it.

In its press release, Avanir said it will conduct another clinical trial with a new formulation of Zenvia that reduces the amount of quinidine per dose from 30 milligrams to 10 milligrams. The company says it believes the drug will still be effective.

Check MDA’s Web site at www.als-mda.org and Avanir’s Web site for details as they become available.

by Margaret Wahl

Steven Perrin, recently named chief scientific officer of the ALS Therapy Development Institute (ALS TDI) in Cambridge, Mass., didn’t start out to be a scientist, although his interest in science goes back a long way. (MDA and the TDI recently formed a partnership to support a three-year, $36 million project to identify biochemical targets in ALS. Read story here.)

Steve Perrin

By the time Perrin, now 42, graduated from Bishop Guertin High School in Nashua, N.H., in 1983, he already knew where his strengths lay — in math, biology and chemistry. Not surprisingly, he decided to become a doctor, entering the premed program at Boston College in 1983.

But four years later, with a bachelor’s degree in biology, Perrin decided to work in a laboratory instead of going straight to medical school. He took a job as a research technician at Boston’s Brigham and Women’s Hospital, extracting DNA from patients’ tissue samples.

The program also involved some clinical training. “We started doing clinical rotations in oncology [cancer] clinics,” he recalls. “I was working with kids and young adults with hematologic malignancies, and I felt it wasn’t the career direction in which I wanted to go.”

Moving away from medicine, he entered graduate school at Boston University in 1991, earning a doctorate in biochemistry four years later.

New Technology

At the time, he remembers, analyzing the activity (“expression”) of 10 genes at a time was considered high throughput. “If someone had asked me to survey a whole genome [all genes],” he says, “I would have laughed.”

The technology that would make such feats possible, however, was on the horizon. In 1995, just as Perrin was finishing his doctoral program, scientists at Stanford (Calif.) University published a paper describing “a high-capacity system to monitor the expression of many genes in parallel.”

This system, known as microarray technology, ushered in a new age, in which thousands of genes would eventually be examined simultaneously, at first for their levels of expression; and later on, for their composition.

About that time, the pharmaceutical company Hoechst Marion Roussel opened one of the first pharmaceutical genomics centers, in Cambridge, Mass. “At the time my academic lab was doing gene analysis the old-fashioned way,” Perrin says. “Hoechst Marion Roussel wanted to set up high throughput technology.”

Perrin was hired to get the job done. In those days, he says, “there were no commercial software programs for computational analysis. We hired mathematicians and statisticians to develop custom software to analyze gene expression data.”

Eventually, Hoechst Marion Roussel merged with other companies and ended up employing 90,000 people at 27 sites around the world, and Perrin was spending a great deal of time traveling. At the same time, he felt his career was becoming too focused on technology alone, and he wanted to get back to integrating it with biology.

In 2000, he left and joined Biogen, another Cambridge, Mass., firm. “They had only 3,000 people, all in Cambridge. They didn’t yet have gene expression profiling in 2000, so I had to set it up from scratch. But by this time the technologies were more mature, and we did it much more quickly.”

A Three-Pronged Approach

At the TDI, Perrin plans to use genetics, the analysis of genetic variance; genomics, the analysis of gene expression; and proteomics, the analysis of protein levels and functions, to sort out the ALS disease process.

His team will examine tissue samples from ALS patients and multiple mouse models of neurodegeneration, moving beyond the commonly studied SOD1 G93A mouse, which has a specific ALS-causing mutation in the SOD1 gene. A very small percentage of human patients have this familial form of ALS.

A Unified ALS Hypothesis

Perrin says he has a hypothesis about ALS that originates with the SOD1 mutant mouse model but that he believes doesn’t end there.

“I think mutant SOD1 ends up being a sticky protein that gloms onto structures in the cell, such as mitochondria, the endoplasmic reticulum and the axonal transport machinery,” he says, referring to parts of nerve cells that produce energy and move compounds from one point to another.

“My hypothesis is that it’s the same for sporadic [nonfamilial] ALS. A sticky protein makes cells unhappy; the cell doesn’t know what to do; microglia [cells of the immune system] get activated; and motor neurons die.

The question is, for sporadic ALS, what’s the protein? And, do you have to understand the mutated proteins, or is there a strategy to help motor neurons deal with sticky or misfolded proteins by regulating some other pathway?”

Perrin, of course, hopes there is.

“This is the first time that we’re taking an unbiased, comprehensive approach to ALS disease biology,” he says. “We’ll tackle it on a scale that hasn’t been described for ALS, or for any disease.”

ALS Awareness Month Preview

The month of May again heralds ALS Awareness Month throughout America, and both MDA and those affected by ALS will be getting out the word to heighten public understanding of ALS and what’s being done to battle it.

Pamela Rayer

Following are a variety of programs that MDA will launch in May to highlight ALS:

•  Expanded ALS Web site. The Web site www.als-mda.org is being expanded to provide new information resources for people with ALS and others affected by it, such as family members and caregivers.

•  ALS Media Kits. These will be used in conjunction with the “ALS: Anyone’s Life Story” series. MDA’s Public Relations Department will send press releases to news media in cities where people profiled in the series live. Media then can follow up with their own expanded stories about these ALS movers and shakers.

•  Public Service Announcements. Public Relations will send advisories to news media reminding them that supporting print and video public service announcements — all ready for immediate use — will be available on MDA’s Web site (www.als-mda.org/media/).

Publications also play an important role next month.  A new ALS Division brochure that lists MDA services and research programs will roll off the press. Another new publication will provide a timeline of ALS research history.

MDA offices will have stocks of information about ALS for public distribution, complemented by eye-catching displays of banners and posters.

For all who have a stake in the fight against ALS this is the opportunity to make friends, business associates and elected officials aware of our determination and the need for their help in finding treatments and cures for a terrible disease.          

Be sure to check the May issue of the MDA/ALS Newsmagazine for a list of special events connected with ALS Awareness Month nationwide as well as detailed information about MDA’s ALS program.

‘ALS: Anyone’s Life Story’ Series

As another way to commemorate the 16th annual ALS Awareness Month, MDA is planning to launch a series called “ALS: Anyone’s Life Story” during the month of May. The series will feature the stories of individuals affected by ALS.

Eric Barb	Lisa Shelley

MDA’s ALS Division Web site (www.als-mda.org) will feature the short profiles and photos of 31 people (one for each day). Inspired by MDA ALS Division Co-Chairperson Augie Nieto, the series will highlight how receiving a diagnosis of ALS has brought a new significance and perspective to each individual’s life.

Here are three of those featured in the series:

Pamela Rayer of Goddard, Kan., is an artist who owns a stained glass business with her husband, Randy. After she was found to have ALS in May 2001, Rayer, 46, learned that the little things aren’t as important as she once thought.

Living with his wife, Lisa, and two daughters, Ashley and Megan, in Olathe, Kan., Eric Barb, 36, received a diagnosis of ALS in May 2000. His goals in life shifted from working and earning things of material value to spending quality time with his family.

Lisa Shelley lives with her husband, Ken, in High Point, N.C., and her diagnosis of ALS in February 2006 has made her realize the importance of each day. Shelley, 45, tries to make a difference each day with her program called Friends Like Mine.

Living With ALS

Daniel Dandignac

With all the plans for ALS Awareness Month, don’t forget that MDA has four weekly Living with ALS chats that allow people with ALS and their caregivers to share friendship, information and support.

Daniel Dandignac (dannyd) of Leander, Texas, is one of nine Living with ALS co-hosts. Dandignac, 48, who received a diagnosis of ALS in 2000, says he began co-hosting the chat in 2004 as a way to reach out to people with ALS around the world.

“Our purpose has always been to be a place where folks could come and talk to people who understand the issues they’re going through,” says Dandignac, a retired paramedic. “We offer moral support, solutions to difficulties they may be facing or just chitchat about whatever comes up that day.”

Dandignac, who’s ambulatory with a walker and uses a power wheelchair for long distance, says the chat also offers resources and helpful information about Medicare, durable medical equipment, feeding tubes and other topics of interest to people affected by ALS.

Check out the Living with ALS chats on Mondays from 3 to 6 p.m., and 9 to 11 p.m.; Wednesdays from 7 to 10 p.m.; and Sundays from 3 to 6 p.m., all EDT.

EQUIPMENT CORNER
Microsoft Windows Vista
Speech-Recognition Feature Enhances Windows Experience

by Alyssa Quintero

Microsoft’s new Windows Vista operating system hit the market in late January, offering a renewed focus on functionality and convenience for users, including people with physical disabilities, according to the company.

In addition to the standard accessibility features like on-screen keyboards, sticky keys and text-to-speech capabilities, Vista has incorporated a new integrated speech-recognition system.

Depending upon whether you’re upgrading from Windows XP, or you’re loading the full version, you could spend anywhere from $100 to $400 on Vista.

Accessibility & Functionality

Windows Vista’s Ease of Access Center features many of the same accessibility features offered in Windows XP; however, Vista has made it easier for people to locate the features in a one-stop-shop location.

The center, which replaces the accessibility wizard, accessibility control panel and utility manager in previous versions, provides a single location where users can quickly get to accessibility settings and tools. To try an accessibility tutorial, visit www.microsoft.com/enable/training/windowsvista.

The center also includes a new, optional questionnaire, and on the basis of your answers, Vista provides a personalized list of recommended accessibility settings and programs. The questions relate to eyesight, dexterity, hearing, speech and so on. The questionnaire helps remove from Vista the guesswork in selecting settings associated with Windows XP, Microsoft says.

“Based on your daily experiences, Windows can provide some options for improving accessibility,” explained Rob Sinclair, Microsoft’s director for the Accessible Technology Group (ATG).

Listen to My Voice

Vista’s new integrated speech-recognition technology provides a hands-free computing experience, especially beneficial to people with ALS who are experiencing severe hand and arm weakness but can still speak. You can dictate documents and e-mails, navigate the Internet, and command applications and the operating system by simply “saying what you see.”

“Most of the accessibility features already exist in some capacity on Windows XP, so that’s not a compelling reason to upgrade, but the speech-recognition feature definitely is a fantastic reason to upgrade,” explained Sinclair, who used the speech-recognition program when he returned to work following shoulder surgery.

For example, you can control applications and complete tasks, such as formatting and saving documents; opening and switching between applications; and opening, copying and deleting files. You also can browse the Internet by speaking the names of links.

Sinclair suggests using a headset with a microphone to reduce interference and increase effectiveness. He also said that Vista’s state-of-the-art voice recognition accuracy is designed to improve as people use it, adapting to their speaking styles and vocabularies.

A five-minute speech recognition demonstration is at www.microsoft.com/enable/demos/windowsvista/speech.aspx.

Innovatively, Vista uses the words people speak as they work through the interactive tutorial to “train” the system; it “listens” to your voice while it teaches you how to use the system. The speech recognition tutorial is located at www.microsoft.com/enable/training/windowsvista/srtutorial.aspx.

While some people think that voice recognition software isn’t perfect and often makes mistakes, the designers of Vista believe they’ve found a better solution.

To correct mistakes, the system will fix incorrectly recognized words or phrases by prompting the user to select from a list of alternate words or phrases.

For example, if Vista recognizes your statement “Park the car over there” as “Park the dog over there,” you’d say “correct ‘dog.’” Then, you’d select from a list of the 10 likeliest alternate words. Once you say the number corresponding to the correct word and OK, the system inserts the word into the document.

“One of the most powerful features of the Vista speech- recognition system is its ability to correct in a very natural way,” Sinclair said.

“It keeps track of all your contexts, so when it displays a list of alternate options for words or phrases, it’s very accurate. And, you can do everything without ever using the mouse or keyboard.”

You also can give voice commands to the system when you’re not dictating text. For instance, if you’re playing a game like Solitaire, you can speak to select a card and tell the computer where to move it.

Is Your PC Vista-Ready?

Sinclair suggests that if you’re thinking about upgrading from Windows XP to Vista, the best place to start is the Windows Vista Upgrade Advisor (www.microsoft.com/windows/ products/windowsvista/buyorupgrade/upgradeadvisor.mspx). You can download the free Upgrade Advisor software, and it scans your computer to see if it will run Vista.

Before you run the Upgrade Advisor, be sure to plug in any USB devices or other devices such as printers, external hard drives or scanners that you regularly use.

And, if you’re planning to buy a new PC with Vista, Sinclair recommends that you “try before you buy” and visit a Microsoft Accessibility Resource Center. To find a location near you, visit www.microsoft.com/enable/centers/default.aspx.

If you’ve purchased a PC in the last two years, Microsoft says, chances are good that you can run Vista. Here’s what you’ll minimally need: an 800 MHz processor, 512 MB of RAM and a 20 GB hard drive with 15 GB of free space.

And, if you use your AAC device in conjunction with your Windows-based computer or Windows software, Sinclair advises that you contact the AT vendor to verify whether your device’s software is compatible with Vista. Microsoft also has a link on its Web site listing the AT vendors that offer Vista-compatible products.

“It’s important to check,” Sinclair said. “My understanding is that nearly all of those products are transitioning to Vista without any trouble at all. In general, the kind of features that AAC devices use in Windows weren’t radically altered in a way that would cause compatibility problems.”

For more information, visit www.microsoft.com/windowsvista.