ALS Specialists Discuss Clinical Trial Results, Methods at Toronto Conference

by Margaret Wahl

Some 750 conferees, mostly ALS clinical and scientific experts, gathered in Toronto Dec. 1-3 for the 18th International Symposium on ALS/MND (Motor Neuron Disease), sponsored by the British Motor Neurone Disease Association.

Michael Strong, a professor of neurology at the University of Western Ontario, presented the increasingly compelling evidence that ALS is not one disease, but many.

The evidence includes the wide range of survival times; variability in the parts of the brain affected, including nonmotor areas in some people but not others; and the lack of a single genetic factor leading to ALS.

The failure of mouse studies to predict human responses to experimental treatments may be due to the lack of a single cause of ALS among human patients, compared to the uniformity of disease causation (usually, a mutation in the SOD1 gene) in lab mice.

ALS patients typically are grouped by whether their disease is familial or sporadic, by the site of symptom onset and by rate of disease progression. However, these categories aren’t sufficient to reflect the wide variation seen in ALS.

Results of several specific trials were presented, as follows.

Large-scale minocycline trial showed drug is harmful in ALS

Paul Gordon, until recently a co-director of an MDA/ALS Center in New York, presented information on two drug trials.

Paul Gordon, until recently an assistant professor of neurology at Columbia University in New York and a co-director at the Eleanor and Lou Gehrig MDA/ALS Center at Columbia, presented the results of a 412-person, phase 3 trial of minocycline, a drug that had shown promise in ALS-affected rodents and in phase 1 and phase 2 studies in patients. (Gordon is now at the Hôpital Pitié Salpêtrière in Paris.)

Minocycline is an antibiotic used to treat certain types of infections. It also has the ability to prevent a cell “suicide” program (apoptosis) and to dampen inflammation.

Participants at 31 U.S. centers were randomly assigned to either minocycline in escalating doses up to 400 milligrams per day, or to a placebo, for nine months, following a four-month lead-in phase during which patients’ untreated rate of decline in the ALS Functional Rating Scale (ALSFRS) was observed.

ALSFRS scores deteriorated 25 percent faster in the minocycline group than in the placebo group, although survival was the same in the two groups. The rate of ALSFRS decline wasn’t dependent on the dose of minocycline, or if people also were taking riluzole (Rilutek).

Gordon said these disappointing results demonstrate the need to improve both the reliability of animal studies in predicting human responses to treatments, and the ability to use early-phase trials to select potentially beneficial compounds and eliminate useless or harmful ones.

Celecoxib and creatine combination may warrant further testing

Gordon also reported on a trial conducted at Columbia to compare two drug combinations against a historical control group (a similar group of ALS patients, previously observed and not treated with either combination).

Patients were randomly assigned to take either creatine plus minocycline or creatine plus celecoxib (Celebrex) for six months and were evaluated using the ALSFRS each month.

Of 60 people, 58 completed the trial. Average ALSFRS decline in the creatine plus celecoxib group was 5.27 units; in the creatine plus minocycline group, 6.47 units; and in the historical control group, 5.82 units.

The creatine-celecoxib combination was selected for further study.

Ritonavir eliminated, but hydroxyurea may be worth closer look

Catherine Lomen-Hoerth, who directs an MDA/ALS center at the University of California at San Francisco, reported on phase 1 trials of Ritonavir, a medication used for HIV/AIDS, and hydroxyurea.

Ritonavir reduces levels of two compounds involved in cellular waste disposal that are elevated in ALS. Hydroxyurea, which is used to treat leukemia, may prevent damage from astrocytes and microglia, two types of nervous-system support cells. Anecdotal reports from three people with ALS suggested possible benefit.

Participants were randomly assigned to receive either low-dose Ritonavir, high-dose Ritonavir, hydroxyurea or a placebo for six months, followed by an additional six months of observation.

Among 24 enrolled patients, investigators found no significant improvements over placebo among the low- and high-dose Ritonavir groups. However, the hydroxyurea group did slightly better than the placebo group on tests of strength and on the ALS Functional Rating Scale (ALSFRS), and their respiratory scores were better than the placebo group. 

Lomen-Hoerth said they’re considering a phase 2 study of hydroxyurea.

Dutch study warns against Chinese stem-cell treatments

Leonard Van Den Berg, a neurologist at University Medical Centre in Utrecht, Netherlands, reported on followup studies of patients who went to China for treatment with a type of stem cell found in human fetal nasal lining (olfactory ensheathing cells, or OECs).

At Beijing West Hill Hospital and Rehabilitation Center, OECs are injected into the brains of ALS patients, at a cost of approximately $25,000.

A Dutch study followed 12 patients who went to Beijing. Seven reported very short-term improvement in functioning or an increase in strength immediately after the injections, lasting less than a day. Three saw no change, and two said they deteriorated.

ALSFRS scores, respiratory measurements and strength tests resumed a downward course in all cases. Of the 10 patients who later died, median survival time was 2.9 years. One person developed a serious blood clot, and another developed pneumonia.

Van Den Berg recommended that people not seek stem-cell treatments in Beijing. He also reported that the West Hill center has since closed, because the Chinese government considered it too “mercantile.”

Strenuous lifestyle may increase ALS susceptibility

Agnes Gonzalez, a research nurse at an ALS center in Montpellier, France, described her team’s study, in which preliminary results suggest that consistent strenuous activity over decades may increase one’s risk of developing ALS.

When Gonzalez and her colleagues studied 51 ALS patients and 40 people with other neurologic diseases, matched by age and gender, they found that those with ALS had expended significantly more energy in their daily lives over the course of three decades, starting at age 20.

Gonzalez said it appears that regular and intense daily activity is a more common way of life for people who develop ALS than for those who don’t. She hypothesized that decades of heavy work or other strenuous exercise could create a deficit of blood flow or oxygen in relation to nerve cells’ demands. Gonzalez emphasized that a final analysis will include many more people with and without ALS.

Nose may provide window to brain

There was general agreement at the meeting about the need for more convenient and precise ways to measure ALS progression and response to treatment.

Jeffrey Rothstein, an MDA research grantee and director of the MDA/ALS Center at Johns Hopkins University in Baltimore, reported on a new technique involving biopsies of nasal tissue that may provide better information about how nerve cells respond to experimental treatments.

Rothstein found cells that he believes are the same as nervous-system astrocytes in the nasal lining and says the new technique might be useful in testing drugs that modify astrocyte activity.

Portable device might make trials easier for participants

Edward Kasarskis, professor of neurology at the University of Kentucky in Lexington, presented his group’s study on the use of a lightweight, portable device called an accelerometer that provides quantitative information about muscle movements.

Thirty-four people with ALS and 10 without strapped Actical accelerometers to each limb and went about their daily activities. Data from the devices were compared with muscle-mass measurements, manual muscle-testing measures and self-ratings of movements.

Investigators concluded the accelerometers have the potential to be used for outcome measures in trials and could minimize participants’ travel and reduce dropout rates.

Multiple Serious Head Injuries May Increase Risk of ALS Incurring multiple head injuries severe enough to require medical attention could be an ALS risk factor, suggests a study by the National Institute of Environmental Health Sciences (NIEHS) of the U.S. National Institutes of Health (NIH). The study supports observations from other studies, including one that found an elevated incidence of ALS in Italian soccer players. However, the authors interpreted their results cautiously, due to the small study size.  NIEHS scientist Honglei Chen and colleagues, who published their findings Oct. 1 in the American Journal of Epidemiology, compared 109 people with ALS in the New England area with 255 people without ALS, matching the study participants with respect to age, gender and region of New England. Those who had sustained more than one severe head injury, with the last one occurring within the previous 10 years, developed ALS 11 times more often than those who had never sustained a severe head injury. People who had sustained just one head injury developed ALS at about the same rate as those who had never had a head injury. Injuries to other body parts weren’t correlated with ALS. It’s unclear how head injury could lead to ALS, but investigators offered several possibilities, including: inflammation of the injured area; disruption of the normal barrier between the circulatory system and brain (the blood-brain barrier); and damage to the energy-producing centers inside cells (mitochondria). They say studies with larger numbers should be undertaken, with more detailed information about each episode of head injury.

"The two offices of memory are collection and distribution." ~ Samuel Johnson

by Amy Labbe

As people grow older, their thoughts often turn to philosophical questions of life, death and the nature of human existence and experience. Many examine their lives, wondering about the significance of their accomplishments and their value to others. Often, these musings fuel an overwhelming desire to tie up loose ends and, more importantly, to make a mark that will endure long into the future.

An ALS diagnosis can accelerate this urge to cull through memories and somehow fashion the best, most important of them into an organized collection.

Through traditional means such as journals, photo albums and scrapbooks, and through more modern methods — audio and video recordings, Weblogs (blogs) and Web sites — people with ALS have gathered their memories and bound them together with an assortment of tape, glue and server space, to be shared and passed on to family, friends and others.

From the self-described “geek” to the technologically challenged, there’s a memory-collecting method out there for everyone. Here’s some advice from those who know.

Sticking with tradition: journals, scrapbooks, etc.

Journals and handwritten letters, photo albums and scrapbooks, drawings, paintings — even poems — can house the memories of the one who creates them. There’s something cathartic in the experience of pouring one’s soul into these sorts of projects.

Darlene Bates feels "a sense of accomplishment" knowing her history and her memories will be passed on to her family.

Darlene Bates, 59, of Edmond, Okla., is putting together a series of scrapbooks to illustrate her family’s history. The first is nearly finished and covers her great-grandparents in the late 1800s through 1974.

“I’m making it for my girls,” she says, adding that she hopes her adult daughters receive “joy and satisfaction” from the gift of memories she’s passing on.

Having lost the use of her arms and hands to ALS, Bates relies on daughters Jane Boyd, also of Edmond, Okla., and Susan Boston of Unionville, Va., to help work on the books. She relates the names, dates and other important information as they tape photos to pages and annotate the details.

Bates offers the following tips: “Get started! Buy lots of supplies. Find someplace to work on it where you can leave it out — that way you don’t spend a lot of time getting ready every time you want to work on it.”

Also into scrapbooking is Tammy Brown, 35, of Thida, Ark., who learned she had ALS in December 2004.

“I got to thinking about leaving things for my family when I pass away so that they can remember me when I’m gone,” Brown says. “I want my children to remember all of the time our family spent together and all of our favorite memories.”

“I have a video for each one of my children so they can hear my voice when they are missing me in the future,” Tammy Brown says. “They will be able to hear me say, ‘I love you.’”

Brown has made four scrapbooks for her 12-year-old daughter, Lauren, and four for her son, Logan, 9. She and her children also are putting together a book specifically dedicated to their family’s journey with ALS, with mementos from walk-a-thons and fundraisers, articles they’ve written for their local newspaper and notes from family members.

Brown also has written journals to her children, telling them stories about things they did, and has made several videotapes as well.

“I’m not sure how long I’ll have to tell them,” she says, “so I try to do different things.”

Brown also advises starting early, before the disease progresses too far.

“Use your own handwriting in a journal while you still can,” she notes, “so your loved ones can have a part of you no matter what happens.” 

Modern media: blogs, videos, etc.

The Web site www.soniasays.org includes pictures, videos, ALS resources and two blogs - one written by Sonia Victorio and the other by her son and caregiver Daryll Victorio - all incorporating a unified theme.

The Internet, blogs (online journals) and Web sites can act as the repository and viewing medium for memory collection and storage. Audio and video recordings and digital photo collections also can be posted and hosted on the Web.

Sonia Victorio, 56, of Grayson, Ga., and her son and caregiver Daryll together keep up blogs and a Web site (www.soniasays.org), where friends, family and strangers can read their thoughts about Sonia’s battle with ALS.

Daryll designed and manages the Web site, which hosts the blogs (updated once or twice a month), information and updates about Sonia, links to ALS resources and a “So You Say” forum where anyone can share their ALS story.

“I’m not trying to memorialize my mom,” Daryll says. “But at the same time, I want what is written to last so that people who knew her can remember her through what I write.”

Both Sonia and Daryll recommend trying out blogging on one of the free blog-hosting Web sites such as Blogger (www.blogger.com) or WordPress (www.wordpress.com).

“These are highly customizable and easy to use,” Daryll says. “Also, read through some blogs to get a feel for the style and medium, especially if you’re at all worried about your skills as a writer.”

Scott Stafne of Woodbury, Minn., also a blogger, says he started jotting down his thoughts online shortly after learning he had ALS in 2004, “primarily to put my voice ‘out there’ while I still could.”

Stafne, 35, also keeps a journal, and he and his wife, Kirsten, have several photo albums on DVD, print, and online, as well as a Web site (http://stafnes.com).

Scott Stafne says sharing his life experiences through his blog and Web site helps him come to terms with the “practical and philosophical aspects of not only living with a fatal illness, but finding peace with both living and dying.”

“It’s a great way to share my experience with other people,” Scott says. “We intend to keep all of it for our children [Eva, 2, and a baby girl due in March] to look at and read in the future.”

Although Kirsten designed their Web site from scratch, Scott notes there are various tools available for setting up Web sites and blogs easily and at minimal cost. Sites such as Yahoo’s GeoCities (http://geocities.yahoo.com), Freewebs (www.freewebs.com) and Bravenet (www.bravenet.com) offer free Web hosting as well as the tools (html codes for adding message forums, links, polls and templates, for example) and tutorials to create and customize your own Web site.

Another of Scott’s projects is the video “Legacy,” made from clips taken from the more than 100 tapes of his life that he’s shot since his diagnosis. The project is posted online at Google Video, and can be easily accessed by clicking a link on the Stafnes’ Web site. “Legacy” was shown at a fundraiser screening of the documentary film “So Much So Fast” (about Stephen Heywood and the ALS Therapy Development Institute) last May in Minneapolis. 

“First and foremost, I’m doing this for our children, so they’ll have a sense of who their dad is and what life was like before they remembered it,” Scott says. “But I certainly want to communicate and share with family and friends and other ALS patients, as well as raise awareness about ALS and living with a fatal illness for a greater community of readers.

“There’s just a need that I have to feel like I’ve contributed something positive, yet honest, to the world before I die. I also do it because it helps me to process my emotions and learn from my experiences.”

Scott says that in this day and age, it’s only getting easier to preserve memories and document one’s life. He recommends that everyone consider doing some sort of legacy project, whether they’re dealing with a fatal illness or not.

“Even if you can’t speak, you still have a voice,” he says. “My advice would be to find an avenue that you’re passionate about and comfortable with and not put too much pressure on yourself, and have fun with it — better to have something to share than nothing at all.”

Charitable Gift Annuities A charitable gift annuity allows you to make a charitable gift and supplement your income with fixed payments for life.  Gift annuities can be established with as little as $10,000. In exchange, MDA pays a pre-specified amount for life to one or two beneficiaries (annuitants must be at least 65 years old when payments begin).  You also receive an immediate income tax deduction for a portion of your gift. To request a gift illustration, call MDA’s Planned Giving Department at (800) 223-6011 or e-mail philanthropy@mdausa.org.

Keep On Keepin’ On
Wheelchair control upgrades keep you moving

by Alyssa Quintero

Thanks to advances in assistive technology, there’s a world of innovative ways to control your power wheelchair and stay active on four wheels.

Planning for change

From the outset, work with your health care team — physician, physical therapist (PT), occupational therapist (OT) and a reliable rehab technology supplier — to select a wheelchair with expandable electronics.

“The disease changes so quickly, but it helps to plan ahead,” says Jenny Robison, a PT and certified assistive technology practitioner (ATP) at the MDA/ALS Center at Vanderbilt University Medical Center in Nashville, Tenn. “We can find ways for people to drive their chairs for a long time.”

Because it takes time to file for insurance and order new equipment, it’s important to keep the health care team apprised of any changes in your functional abilities, such as difficulty using the joystick. Otherwise the control method may become unsafe for you — and everyone who crosses your path — before a new system is in place. And it’s valuable to work with a new control system before it’s required full time.

Knees and jaws

With patience, Steven Nichols keeps moving with his single-switch scanner.

After using a standard joystick and head array, Steven Nichols, a software engineer from Clifton, Va., now drives his Permobil chair via a single-switch scanning system manufactured by PG Drives Technology (www.pgdt.com), of Anaheim, Calif.

Nichols, who has some movement in his legs, activates the scanning system by squeezing his knee against a button. The system then scans through the various options — forward, right, reverse, left and menu (which accesses tilt, recline and seat elevation). The choices are displayed on an LCD screen attached to the right side of his wheelchair. When the scan reaches the desired option, Nichols presses and holds the knee button and the chair drives forward, turns, etc. His current scanning rate is set at .75 seconds.

“The advantages to using the system far outweigh any disadvantages,” says Nichols, 57, who hasn’t had arm, hand or shoulder movement since 1999. “It can be operated with very limited mobility and strength, it’s fully integrated so the user can drive and control all wheelchair functions, and it has a built-in alarm that beeps with each switch selection.”

Nichols admits that the scanning system requires patience while waiting for a desired option to appear, and any function other than straight-line driving is extremely slow.

Still, he says, “With this system, I’m able to move freely inside and outside of the house without assistance, which is a key to maintaining independence.”

Jack Hurst flexes his jaw muscle to drive his chair.

Jack Hurst of Marietta, Ga., received an ALS diagnosis in March 1987 and used a manual wheelchair for 18 years before switching to an Invacare TDX3 power chair in November 2006.

Hurst, 69, now uses a single-switch scanner from Adaptive Switch Laboratories (www.asl-inc.com), of Spicewood, Texas, that’s operated with an EMG (electromyographic) switch. The switch is attached to his face using an electrode and sensor sticker, and reads the impulses from his jaw muscle to drive.

To activate the system, Hurst flexes his jaw muscle, and when the indicator light reaches the desired selection, he bites down and holds to carry out the function.

Before settling on his current system, Hurst first tried a fiber optics switch, but it worked too well. Once he activated the switch and started driving, he couldn’t stop.

“I tried to control the fiber optic switch by smiling,” Hurst said. “I could start the wheelchair fine, but I couldn’t stop smiling to stop. That made me dangerous to myself and others.”

A customized solution

David Jayne of Rex, Ga., has used a power wheelchair since 1993. Two years ago when he lost the ability to safely control his Invacare wheelchair with the original five-switch system, he searched for customized controls.

“The loss of independent mobility was excellent motivation to develop a solution,” he says.

David Jayne controls all wheelchair functions via his laptop.

Jayne, 46, can’t move his head, so looking at a small monitor to his right wasn’t a possibility. He wasn’t impressed by the expensive, slow, off-the-shelf scanning systems that don’t step scan. Step scanning allows for faster operation because the software scans rows of characters rather than each individual character. When the row containing the desired character is reached, the user activates the switch to scan each character in that row only.

Jayne considered the ERICA eye-tracking system from Eye Response Technologies, but it didn’t work effectively for him in different lighting without recalibrating the camera.

“I can’t control my head, so it’s positioned to look forward with headrests. One day, staring at the laptop screen, I had an epiphany — enable the laptop to communicate with the chair’s computer.”

It took him years to find a way to do this, but thanks to a friend who discovered a USB digital input/output module that communicates the laptop’s commands to the chair’s computer, Jayne is on the move again.

Since September, he’s used step-scanning software which displays the wheelchair functions and a directional grid on his wheelchair-mounted laptop. To send commands, Jayne has a fiber optics switch mounted on his glasses, which he activates by raising his eyebrow and “doing my best Groucho Marx impression,” he says.

Jayne says his system provides efficient access for single-switch users, and that it’s more accurate and easier to drive with the directional grid.

“It’s tremendously convenient to operate all systems from the laptop, including communication, environmental controls, cell phone, Internet, e-mail, chair functions and mobility,” Jayne says. “If an individual uses an augmentative communication system that incorporates a laptop, I definitely recommend this system because of the sophistication and ease of use.”

Jayne notes that one possible disadvantage to his one-of-a-kind setup is that it runs on a Windows operating system, which could crash while driving. This hasn’t happened, but just in case, Jayne has an additional switch that will disable the chair and prevent a disaster.

“The scanning driving system has restored my mobility, enabling me to embark on an endless list of independent activities,” he says. “I’m driving better than I ever have!”

If you’d like to learn more, e-mail Jayne at david@respitematch.com.

Special ALS packages

Systems range in price from $1,500 to $10,000, so it pays to look around and consult your health care team before buying.

Because it takes three or four months to receive equipment, start your research early, advises Jenny Lieberman, an OT and certified ATP at the MDA/ALS Center at Mount Sinai Hospital and Medical Center in New York City. She suggests exploring the latest innovations by trying equipment at disability expos, and testing controls with your clinic team.

Some companies have programs to assist people with progressive diseases like ALS. For example, Adaptive Switch Laboratories offers an ALS Drive Control package for $7,200. As the user’s abilities change, the company will provide different systems at no additional charge, swapping out a joystick for a head array, for example.

Switch-It (www.switchit-inc.com), of Missouri City, Texas, offers a special five-year lease program for $5,600, which allows an individual to exchange an input device for another that’s more appropriate.

Besides your OT and PT, you can find local certified assistive technology practitioners and suppliers by visiting the Rehabilitation Engineering & Assistive Technology Society of North America’s Web site at www.resna.org and clicking on “AT/ATS/RET Directory” or by calling (703) 524-6686.

To locate certified rehab technology suppliers (CRTS) who provide complex rehab and AT products and services in your area, visit the National Registry of Rehabilitation Technology Suppliers at www.nrrts.org, or call (303) 948-1080.