ALS Research Roundup

by Margaret Wahl

Investigators in the laboratory of Jean-Pierre Julien at Laval University in Quebec have developed a new way to block abnormal SOD1 protein molecules, which cause SOD1-related ALS. (Researchers elsewhere will soon block erroneous genetic instructions for SOD1.)

Although ALS resulting from a mutation in the SOD1 gene accounts for only about 1 percent to 3 percent of all ALS cases, it’s by far the best understood form of the disease, and the one on which most ALS mouse models are based.

In a paper published online Feb. 2 in Proceedings of the National Academy of Sciences, the scientists describe how they developed and tested vaccines against two types of SOD1 abnormalities.

First, they immunized a group of mice carrying a mutation known as G37R in their SOD1 genes by injecting them with abnormal SOD1 protein molecules along with a substance that stimulates the immune system.

Treated mice received three of these injections a few weeks apart, while a comparison (control) group received a salt solution with the immune system stimulant. The mice that received the SOD1 protein molecules lived an average of a month longer than those that got the salt injections.

However, when the scientists tried the same approach, but with a different type of abnormal SOD1 (the G93A mutation), in mice with extremely high levels of mutated SOD1 protein, the benefit was negligible.

They decided that, with this type of ALS-affected mouse, instead of trying “active” immunization, in which animals mount their own immune response, they would try a “passive” immunization approach, giving the mice ready-made immune system weapons known as antibodies, designed specifically to attack abnormal SOD1. They put the antibodies directly into the nervous system, rather than injecting them under the skin.

The second approach prolonged the lives of the treated G93A mice by a week compared to a control group, and it significantly delayed the usual loss of body weight and impairment of leg function.

The researchers say the vaccination approach, especially a passive immunization based on specific antibody administration, “merits consideration” in people with SOD1-related ALS. They note that such patients have much lower levels of mutated SOD1 protein than do the G93A mice used in these experiments.

Large Trial Will Test Diaphragm Stimulation Strategy

A new, 100-person trial to test the effects on respiratory function of electrically stimulating the ALS-affected diaphragm is now under way at several centers.

Raymond Onders at Case Western Reserve University in Cleveland and colleagues say they’ve now implanted electrodes in the diaphragm muscles of 14 people with ALS and found the strategy slows the decline of respiratory function and delays the need for tracheostomy.

For the new study, Onders and colleagues are seeking 100 people with ALS who have a forced vital capacity (respiratory test) of 50 to 85 percent of normal at the time of screening, don’t have impaired decision-making ability, aren’t markedly overweight, and meet other criteria.

For more information, contact Mary Jo Elmo at Case Western, at (216) 844-8594 or maryjo.elmo@uhhs.com; and/or go to www.mda.org and click on Clinical Trials from the home page.

CytRx to Determine Maximum Safe Dose of Arimoclomol

CytRx (www.cytrx.com), a Los Angeles biopharmaceutical company, announced in a Feb. 6 press release its intention to determine the maximum dose of its experimental drug arimoclomol that can be safely administered. The company then plans, if the U.S. Food and Drug Administration approves, to test the effectiveness of that dosage in people with ALS.

Arimoclomol is designed to stimulate production of molecular chaperones, which repair damaged proteins or tag them for disposal. Chaperone proteins are critical for survival of stressed cells.

In September, arimoclomol was found to be safe and well tolerated in a trial that wasn’t designed to test efficacy.

If the data from the maximum dose study (conducted in healthy volunteers) support moving arimoclomol into an efficacy trial in ALS, the company will ask for FDA approval to begin this type of testing.

Arimoclomol stimulates production of chaperone proteins, which attempt to maintain quality control by repairing damaged protein molecules; or, if they can’t, tag them for a cellular disposal system. Heather Durham at Montreal Neurological Institute, a longtime MDA research grantee and member of the Association’s Medical Advisory Committee, has conducted much of the fundamental research on protein quality control mechanisms and ALS.

Italians With ALS Have Access to New IGF1-Based Compound

In January, the Italian Ministry of Health asked Insmed (www.insmed.com), a Richmond, Va., biopharmaceutical company, to make its drug Iplex available to ALS patients in Italy. The request has been granted.

Iplex is a combination of insulinlike growth factor 1 (IGF1) and IGF binding protein 3. It’s approved by the U.S. Food and Drug Administration to treat certain types of growth failure in children, and it’s also being tested in people with myotonic muscular dystrophy

Almost all IGF1 that circulates in the bloodstream is attached to IGF binding protein 3, so the combination may be a better mimic of human physiology than IGF1 alone.

IGF1 is being tested alone in a large-scale, multicenter trial in ALS, for which data analysis is scheduled to begin this summer. That compound, known as Myotrophin, failed to meet criteria for FDA approval in two earlier trials.

Some 50 people with ALS in Italy are receiving Iplex through Insmed’s “expanded access” program. “We hope data collected from the Italian patients who are participating in this expanded access program will be useful for further clinical development of Iplex and/or IGF1 for this indication,” said Geoffrey Allan, president and CEO of Insmed.

Back to top

by Kathy Wechsler

An avid traveler who fell in love with England and Ireland, Robert “Bob” Bussey of Bath, Maine, runs a British goods store called Bridgham and Cook Ltd.

A Change of Plans

Bussey, 62, who received a diagnosis of ALS in September 2000, worked in the Freeport store from its opening in 1987 until 2003, when he began using a wheelchair and could no longer get into the congested store. From that point on, he’s run his store from home with his laptop computer, while Anne, his wife of 18 years, and a devoted staff of nine, hold down the shop.

Bob Bussey’s store, Bridgham and Cook Ltd., specializes in goods from Britain and Ireland.

Now paralyzed except for the good range-of-motion of his head, Bussey still uses his laptop from his bed to choose which products to sell, order products, and do inventory control for the store. He runs the store, checks his e-mail and reads the newspaper with a hands-free program that allows him to control the cursor by moving his head.

Because his speech is difficult to understand, Bussey’s computer is programmed with communication software that activates a voice with a British accent.

Determined to Succeed

Today, Bridgham and Cook Ltd., opened by Bussey and his brother, Bill, carries groceries, clothing, toiletries, pub gear and gifts popular in England and Ireland and has a steady flow of local customers and visitors from across the country.

Customers also shop and order online at www. britishgoods.com. The store has thousands of online regulars from the United States and Canada as well as the occasional shopper from another continent. Many online regulars are British or Irish customers who live in the United States and miss the food and specialty items they grew accustomed to in their native countries. 

From the success of Bridgham and Cook Ltd., you’d never guess that an electrical fire in September damaged all of the store’s merchandise and the building itself. A new location was found two days later. Anne took digital photographs of the new space and showed them to Bussey, who used them to redesign his store on his laptop.

It turned out that the new store location was larger and easy to spot from the street, whereas the old store was tucked around a corner and hard to find.  The new one is right on Main Street. 

“This new edition of the store is so beautiful and successful that everyone associated with it, most especially Anne and me, is feeling rejuvenated, as if it’s a totally new enterprise,” says Bussey. “I feel a great deal of satisfaction in its rebuilding, even though I am motionless in bed. 

“It would be wonderful if every ALS patient could continue to feel such feelings, however that may happen.”

by Phyllis Silver

In the February issue Stan Silver wrote “In the Beginning,” his coming to an understanding of ALS and how he would live with it. This month his wife, Phyllis, writes of confronting the emergence of her role as Stan’s caregiver.

Phyllis and Stan Silver

Stan is an even-tempered person with an easy smile and dry humor.  He’s a creature of habit and isn’t comfortable with change.   But gradually his body altered and bent over.  His hands and legs weakened, yet we were stymied by what was happening.  It was so hard to fight the unknown, and then his diagnosis of progressive muscular atrophy (PMA), of ALS, was made.

Stan surprised us all with his ability to cope with and adapt to monthly, weekly and sometimes even daily changes, and maintain a positive attitude. In the meantime, I dealt with everything in my own way — with chocolate and humor — as I discovered time wasn’t my own but belonged to caring for Stan in every way.

I was ready to rejoin the work force, or so I thought, as I waited for Stan’s condition to improve or level off.  My reality check came the day I walked into the bedroom and saw Stan using his teeth to pull up the sheet. I was crying on the inside but remained calm on the outside, realizing his frustration and how upsetting this was for both of us. And he still was only at the beginning of this journey with ALS.

Was I resentful? No, I was just disheartened to witness what was happening to my husband while sometimes feeling overwhelmed and helpless.  I once taught time management, yet now I feel that time is controlling me, and I can’t seem to develop a routine because of the constant evolution of Stan’s need for care.

I’ve learned I can’t be a caregiver alone, and I don’t need to be. The MDA support group has been very beneficial to both of us.  The other caregivers share experiences, ideas, laughter and tears. One caregiver gave me special silverware that she thought would be easier for Stan to hold, but the progression of the disease allowed him only a short time to use the utensils. The MDA representative at the support group, MDA Health Care Service Coordinator Jackie Puerta, is warm, helpful, and genuinely concerned for all of the people with ALS and their caregivers. Our relatives and friends have also been very supportive, with many of them visiting from out of town as well as calling frequently.

Right before the New Year holiday weekend, Stan’s new power chair just stopped working.  I called the MDA office, and Health Care Service Coordinator Sarah Lindenmoth arranged for a manual chair to be delivered so Stan, who was stuck in bed, could join our company for dinner.  The next day MDA delivered a loaner power chair for him to use until his own chair was fixed. 

To me MDA stands for Many Deeds Accomplished.

Stan and Phyllis Silver live in New York. Phyllis has taught kindergarten and second grade and worked in college administration and corporate training. Her new career is full-time caregiving.

by Kathy Wechsler

Losing the ability to speak is a harsh reality for people with ALS. It happens at different times for different people, depending on where the ALS symptoms appear and how fast the disease is progressing.

It’s also important to realize that preparing for loss of the ability to speak is psychologically and emotionally challenging, says Erika Sauer, a speech-language pathologist (SLP) of five years who participates in the Kessenich Family MDA/ALS Center clinic held at St. Catherine’s Rehabilitation Hospital in Miami.

The First Step

When to see an SLP depends on your type of ALS onset. Sauer recommends that you see an SLP right away if you have bulbar-onset ALS, because the components of speech production — respiration, phonation [the process of uttering sound] and articulation — are usually affected first. Your breath support is “the battery that runs your voice” and controls the volume of your voice, while the motor production component of speech influences how you articulate.

Colin Portnuff uses AAC devices to compensate for the loss of his voice.

Colin Portnuff of Tualatin, Ore., started working with an SLP soon after he was found to have bulbar-onset ALS in 2004. Portnuff, 55, who has two children, Cory, 24, and Lindsay, 18, with his wife, Laurie Farquhar, experienced speech difficulty as his first ALS symptom.

While reading up on speech production, he came across an article in the 2002 Journal of Medical Speech Language Pathology about how to use a person’s speaking rate as a warning sign for when to begin working with an SLP. According to the article, normal speaking rate is 190 words per minute; when your speaking rate slows to 125 words per minute, it’s time to see an SLP.

If your ALS starts in your extremities, it will probably take longer to affect your voice, and deciding when to see an SLP isn’t so straightforward. In that case, Sauer suggests seeing an SLP when your speech begins to “slow down/slur” and/or you’re having trouble being heard by others. The longer you wait, the more difficult it may become to communicate about your needs and desires. You also want to be able to continue to communicate effectively and efficiently in a variety of environments.

Your SLP will guide you through the rest of the steps to maintaining your communicative ability while your speech declines.

AAC Devices

Although it’s not possible to reverse speech degeneration, your SLP can provide compensatory techniques to make your speech better understood.

“When we speak naturally in connected speech we combine and omit sounds,” Sauer says. “When motor production and breath support decline a patient can improve their speech intelligibility by slowing down their rate of speech production; speaking in small phrases with replenishing breaths instead of long sentences; and concentrating on accurately articulating all the sounds in a word.”

When degeneration of muscle coordination and strength make compensatory strategies ineffective, it’s time to start looking into augmentative and alternative communication (AAC) devices.

AAC devices flood the market. They range from low-tech options  like communication boards and books to high-tech devices like the text-to-speech LightWRITER from Toby Churchill and the complex eye-tracking interface Eyegaze System from LC Technologies. Prices for AAC devices range from the hundreds to the thousands of dollars.

“A therapist who’s trained and knowledgeable in AAC devices is going to recommend a device that is going to grow with the patient,” Sauer says. “When you’re dealing with a progressive disease, you wouldn’t recommend a device that uses just typing and has no switch capability.  What if they can’t use their hands anymore?”

Admitting the need for an AAC device is difficult, but Sauer warns you not to put it off. Getting an AAC device can be a challenge.

“There’s an evaluation process, ordering the equipment, programming and setting up the equipment, and that doesn’t necessarily take place within a week’s time,” she says. “So if you wait until you are moderately affected, and then you have to wait two or three months, you could possibly be severely affected and still not have your device.”

Portnuff began researching the various types of AAC devices in late 2005 and has since addressed symposia as well as published articles about AAC. He now uses a Toshiba Tecra M4 with two speech-generating applications, NextUp Talker and TextAloud.

“If you have bulbar-onset ALS, alternative access methods (other than typing) may not come into play for some time, but keep your options open, because it is hard to predict your eventual needs,” says Portnuff. “If you have limb-onset ALS, you may not be focused on speech issues, but do try to plan ahead.”

Recording Speech

Advances in AAC technology allow some programs to use your prerecorded voice so that you can have your own voice playing on the speech-generating device.

Make sure that you’re ready for such a long and involved process. This can be an emotional task, says Sauer.

“I recently spoke with a patient who wanted to record her voice, but every time she sat down to do it or to write down those things that she wanted to say, it choked her up and disturbed her and she couldn’t do it,” she says.

Nietos to Host MDA/ALS Bash

Augie and Lynne Nieto, co-chairpersons of MDA’s ALS Division, are hosting the Black & Blue Bash for Augie’s Quest to raise funds for MDA’s ALS research program on March 30 at the San Francisco Marriott. Two-time Olympic gold medallist swimmer Summer Sanders will serve as the event’s emcee.  Best-selling author Mitch Albom (Tuesdays with Morrie, The Five People You Meet in Heaven and For One More Day) is the keynote speaker, and Grammy-nominated singer/songwriter John Ondrasik of Five for Fighting will perform. The inaugural Bash in 2006 raised $2.8 million for MDA’s ALS research program — a record amount for any event aimed at fighting ALS. For more information, or to purchase tickets, visit www.augiesquest.org, or call MDA at (714) 550-0161.

WHERE THERE'S A WILL, THERE'S A WAY
Ron and Linda Edwards found a way to help both themselves and others

Ron Edwards of Pryor, Okla., never expected to be the co-owner of a home business with his wife, Linda. With a 38-year career in banking, Ron, 59, was content to be a bank president.

Linda and Ron Edwards

In the fall of 2005, Ron began experiencing muscle weakness in his shoulders and arms, and after rotator cuff surgery in one shoulder, he continued to lose strength rapidly in both arms. In May 2006, he received a diagnosis of ALS.

“At that time, I was still working, and I had a very frustrating day,” Ron said. “I had taken a very important client out to dinner, and I got food all over myself. I got so worn out trying to eat.”

Humiliated and frustrated, Ron told Linda the next morning, “I can’t do this anymore.” Linda promised to find a way to help Ron feed himself.

After an exhaustive Internet search, Linda couldn’t find anything that would work. She and Ron also spoke with some occupational therapists, but they didn’t have a solution. In mid-May, Linda, an avid do-it-yourselfer, went to her workshop to build one.

The Birth of the Arm Thing

Ron recalls that Linda would pop into the house every few hours to see what he thought about her invention, and at the end of the day, she’d developed a working prototype.

Ron Edwards uses the Arm Thing for tasks requiring support for weakened hands and arms.

“Within 24 hours, he had a complete attitude change,” Linda said. “He could feed himself again and not be embarrassed.”

The Arm Thing supports the forearm with an armrest sized to fit the user. The forearm support rests on an aluminum channel and slide, which adjusts the vertical height of the forearm. The armpiece is connected to the aluminum base with a ball-and-socket connection, allowing a 360-degree rotation.

Linda and Ron got a lot of positive feedback from others with ALS who’d tried the device. And after some encouragement from Stanley H. Appel, director of the MDA/ALS Center at the Methodist Neurological Institute in Houston, and Anne Swisher, Houston’s MDA health care service coordinator, they decided to manufacture the device.

“It’s changed Ron’s life, and I want to be able to help others with ALS,” Linda said.

The Edwardses came up with a few professional names, but “nobody liked them, and everybody kept calling it the arm thing.”

Ron said, “It allows me to go out and be with my friends and family. Somebody has to put my arm in the device, but everybody’s used to it. It’s about having a life and maintaining my dignity.”

Making Things Easier

In August, Linda and Ron founded their new home business called MTE (Making Things Easier) Devices, with the goal of helping people with ALS and other physical disabilities “enjoy a better quality of life.”

To make the device more versatile, Linda measured everyone’s arm at her church and took the average size as the basis for each size category. She also tested the device on a wide variety of tables and took the average height of several tables.

Linda then met with an attorney and filed the patent once the lawyer determined that Linda was right — “there was nothing like it on the market even though it’s such a simple idea.”

Ron explained, “I’ve been impressed by Linda’s dogged determination in creating a product that not only will work for me, but will work for many other people.”

Patent Pending

The current model of the Arm Thing, which is washable and easy to clean, separates into two pieces — the armpiece and the aluminum base with a nonskid surface — that are connected using a Teflon ball-and-socket. The armpiece, made of high-density plastic, has a glide to adjust the angle for different table heights. You secure the user’s arm to the device using two nylon straps with hook-and-loop attachments.

Hand-molded by Linda, the armpiece is available in five sizes (XS, S, M, L, XL), and the standard armpiece ($449) extends from the elbow to the wrist. As Ron became weaker, he needed more wrist support, so Linda designed an extended-wrist armpiece ($479) that reaches the palm of the hand. To order, you need to provide Linda with three measurements: forearm diameter, wrist diameter and forearm length.

“We’ve worked to improve the original model as Ron’s become weaker,” Linda said. “With the progression of ALS, we’ve learned that we have to keep adapting the product to make it work for everyone. If there’s a specific need, I’ll work to improve it and adapt it to help a person deal with a particular problem.”

Ron and Linda, who’ll celebrate their 39th wedding anniversary this year, agree that the device “has changed our lives.” And while a patent approval can take anywhere from one to five years, Linda and Ron decided to manufacture the device “because in five years there will be a lot of people that could have used it.”

Linda added tearfully, “I don’t want to wait five years. I don’t know if I’m going to have Ron in five years, and I want him to see that he helped someone else. I want Ron to know that he didn’t go through all of this for nothing.”

Note: With MTE Devices’ Web site still under construction at press time, you can contact Linda Edwards at (918) 825-3363 or lindamte@sbcglobal.net for more information about the Arm Thing.

EQUIPMENT CORNER
Sleep Aids: Low-Tech Strategies for Improving Sleep Comfort

by Alyssa Quintero

For people with ALS, finding innovative ways to ensure better sleep comfort benefits everyone in the household. Proper bed positioning is vital because it helps improve circulation, minimizes the swelling associated with severe weakness and muscle inactivity, and helps prevent skin breakdown (pressure sores). Adequate gentle support and stability also contribute to sleep comfort.

While there isn’t one perfect solution to sleep difficulties, trial and error can produce useful measures that promote effective rest.

Here are some examples of people with ALS who have found low-to-medium tech solutions to the challenges to their sleep that have made a world of difference in their lives.

Thank You, Mattress Genie

Marcie Gibson of Arlington, Texas, is determined to stay in her standard twin bed. Gibson, 36, who uses a 4-inch thick memory foam mattress overlay on top of her regular mattress, has also been using the Mattress Genie for two years and says, “It’s wonderful because it allows me to continue using my bed instead of replacing it with a hospital bed.”

Available through Contour Living (www.contourliving.com), the device is used to lift the head of a mattress up to 40 degrees. It’s available in four sizes ($90-$150), works on most standard mattresses and can lift up to 500 pounds. You can raise or lower the device with the push of a button.

Linda Gibson, Marcie’s mother and caregiver, explained that the bed lift is the best way to elevate Marcie’s head without using several pillows and wedges that may shift during the night. Linda repositions Marcie every two hours during the night, and when Marcie needs to lie on her side, she uses a wedge to support her back, a squishy pillow under her right shoulder and a pillow between her knees.

While the motor on the Mattress Genie sounds like a vacuum cleaner, Linda said you get used to it, especially since it’s enabled Marcie to maintain some control over her environment.

Mattress Overlay Saves the Day

Ron Harrison of Lake St. Louis, Mo., used an alternating pressure mattress and a Tempur-Pedic mattress before finding relief with a gel mattress overlay. The overlay sits on Harrison’s hospital bed; he has the head of the bed raised at a 45-degree angle to help with his breathing and saliva control. 

“My sitting up while sleeping creates a depression (a bowl with a firm rim) in the mattress, which after a while can become very uncomfortable,” Harrison, 71, said. “The gel mattress has worked best to reduce the problem, and I’m able to experience quality sleep time.”

For enhanced head and neck support, Harrison also uses a dual-valve Sleepmatterzzz Cair pillow with Roho shape-fitting technology (www.shapefitting.com) that allows you to adjust the flow of air in the aircells of the pillow. He uses a neck roll on the left side of the pillow to cradle his head, preventing it from falling sideways.

Harrison also uses a Cair pillow to support his feet and a knee-support memory foam pad under the lower leg above the ankles to lift his heels off the bed. He uses a board in front of the pillow for sheet tenting.

Memory Foam Is a ‘Godsend’

Glen Houston of St. Charles, Mo., has been using a memory foam pad in addition to his adjustable, electric hospital bed for more than two years, and “it’s been a godsend.”

“So far, it’s been perfect,” Houston, 66, said. “There’s no pain, and it conforms to your body and supports your whole body.”

In addition to his hospital bed and memory foam pad, Houston’s used several do-it-yourself strategies to find comfort. For example, he and a friend constructed a board with wooden legs that sits under the foot of the mattress. Fully adjustable, the legs are connected to the mattress frame and can raise the mattress an additional six to eight inches.

Glen Houston has arrived at do-it-yourself solutions to sleep problems, such as a foam-lined box to prevent his feet from falling to the side (left) and supports to raise the foot of his mattress (right)

To keep Houston’s feet from falling to the side, a friend constructed a three-sided box lined with two inches of foam. Houston rests his feet inside the box. The U-shaped box is connected to the bed frame and is adjustable. His wife tents the blankets and sheets over the box.

“An ALS patient really needs to have his feet tented,” Houston said. “If the sheet’s too heavy, it can push your feet around, and the weight of the blanket can give you a feeling of claustrophobia because you can’t move your feet.”

Houston’s wife places a pillow under each leg, from his knee to ankle, and she puts rolled towels alongside each pillow to keep his knees from turning outward. Houston uses a pillow under each arm and an old feather pillow under his head. It’s not high-tech, he says, but it does the trick and keeps his head from turning to the side.

Houston prefers knit sheets because they’re thin, lighter and softer than cotton sheets, and he recommends using a cotton-quilted pad on top of the bedsheet for easier positioning.

For information about high-tech sleep aids and a list of sleep aids resources, read “One Good Turn” in Quest, September-October 2006.