ALS Research Roundup

by Margaret Wahl

Organophosphate pesticides, used on some crops, are among the chemicals that are detoxified by PON enzymes.

Flaws in Detoxifying Enzymes Again Implicated In ALS Susceptibility

In the search for genetic variations that predispose a person to developing ALS, a few intriguing examples stand out as worthy of further investigation.

Among them are findings that particular variations in the PON (paraoxonase) genes, located together on chromosome 7 and carrying instructions for enzymes that detoxify certain chemicals, such as organophosphate pesticides, are found more often in people with ALS than in people who don’t have the disease.

MDA grantee Guy Rouleau at the University of Montreal, and colleagues, have recently added to the evidence linking PON variants to ALS.

Studies in 2006 identified certain PON changes as ALS-related in Poland, North America

In 2006, Agnieszka Slowik and colleagues found a combination of two variants, one in the PON1 gene and one in the PON2 gene, occurred 3.4 times more often in ALS-affected Polish subjects than it did in those without the disease.

At the same time, researchers in the laboratory of Teepu Siddique at Northwestern University in Chicago, with colleagues at Vanderbilt and Duke Universities, found a variant sequence of DNA lying between the PON2 and PON3 genes to be associated with ALS in a North American population. These researchers speculated that ALS risk might be altered by a PON “cluster,” rather than by a single variant in a single gene. (See“Detox Enzyme DNA,” ALS Newsmagazine, August 2006".)

New results implicate cluster of PON changes in France, Sweden, Quebec

Rouleau’s group, which published its findings Aug. 12 in Neurology, studied PON genes in people with and without ALS in France, Sweden and the Canadian province Quebec. Their results, like the Siddique eam’s findings, suggest that a cluster of PON variations, not just one, may be responsible for an increase in ALS susceptibility.

The researchers looked at 20 locations in the three PON genes in 480 people with ALS and 475 without ALS in France; 159 people with ALS and 95 without in Quebec; and 558 people with ALS and 506 without in Sweden.

They didn’t find any particular variant to be associated with ALS by itself in any group. However, they did find a cluster of PON gene variants was significantly associated with ALS in the French group, the Quebec group and the combined French, Quebec and Swedish groups.

In the Swedish group, the researchers found PON gene variants were not significantly different in the ALS and non-ALS populations.

They say the different results in the populations studied may mean that multiple combinations of PON gene changes have the potential to raise the likelihood of ALS development, but that different combinations accumulate over time in various populations.

The authors of the newest study say that “variants in the PON gene cluster must be seriously considered as a susceptibility factor to ALS.”

Scientists create nerve cells from skin cells of woman with ALS

MDA grantee Hiroshi Mitsumoto at Columbia University was on the study team that created nerve cells from skin cells.

MDA-supported scientists at Harvard University in Cambridge, Mass., and Columbia University, New York City, have created muscle-controlling nerve cells (also called motor neurons) from the skin cells of a person with ALS.

John Dimos of the Harvard Stem Cell Institute and colleagues published their findings in the Aug. 29 issue of Science. MDA-supported Hiroshi Mitsumoto, who directs the Eleanor and Lou Gehrig MDA/ALS Center at Columbia, was part of the study team.

“Much of the hope invested in patient-specific stem cells is based on the assumption that it will be possible to differentiate [mature] them into disease-relevant cell types,” the study authors say, referring to the process of coaxing a stem cell down a particular developmental path, such as that of a nerve cell.

One goal of such differentiation is the possibility of using such cells to replace the patient’s own, disease-affected cells. Since the replacement cells would come from the patient, the immune system would likely accept them.

Another goal is to study the way in which specific cell types from a disease-affected patient develop, which should provide important insights into the disease process.

The study team collected skin cells from an 82-year-old woman with a familial form of ALS and then “turned back the clock” in these cells, inducing them to become like the cells of embryos, but without the capability of actually forming embryos. After the cells were reprogrammed back to an embryo-like state, the researchers coaxed them to develop into nerve cells.

Other research teams have recently created similar “induced pluripotent stem cells” (iPS), but until now, it wasn’t clear that the process could be accomplished in cells from elderly patients with chronic diseases.

“Our study demonstrates the feasibility of producing large numbers of motor neurons with a patient’s exact genotype [genes], which would be immune-matched to that individual, a long sought-after goal of regenerative medicine,” the study’s authors write. “However, several major challenges must be resolved before cell replacement therapy using iPS technology an become a clinical reality.”

Among these challenges, they say, are ensuring the safety of iPS cells for transplantation into patients, since the current methods used for reprogramming could cause malignancies; and correcting defects, such as genetic errors, that caused the disease in the first place.

Replacing damaged nerve cells involves the additional hurdle of ensuring that the cells go to the right place in the brain or spinal cord and connect to muscle fibers and other nerve cells properly.

Biomarker study opens across U.S.

A study of biochemical indicators (“biomarkers”) uniquely associated with ALS is now open at sites throughout the United States coordinated at Massachusetts General Hospital in Boston. The investigators are seeking adults with ALS, suspected ALS, or neurological diseases other than ALS, as well as healthy adults. Participants will be asked to give blood and spinal fluid samples and meet study criteria. Contact Daniela Grasso at (617) 726- 0842, (877) 458-0631 (toll-free) or dgrasso@partners.org.

UC Irvine professor seeks people who may have rare muscle and bone disorder

Virginia Kimonis, an investigator at the University of California-Irvine, is conducting a study of people with muscle weakness, abnormal clumps called inclusion bodies in a muscle biopsy, and either bone pain with susceptibility to fractures or mental deterioration. This combination, while sometimes diagnosed as possible ALS, may indicate a disorder caused by mutations in the VCP gene. Contact Kimonis at (714) 456-5791, (949) 824-0571 or vkimonis@uci.edu.

MDA/ALS Centers to help ALS TDI identify ALS ‘signature’

Blood and tissue samples will be collected from people with ALS who are seen at three of MDA’s specialized ALS Centers, as part of a collaborative effort between MDA and the ALS Therapy Development Institute (ALS TDI) of Cambridge, Mass.

ALS TDI scientists are planning to identify biological indicators (biomarkers) of disease progression that constitute a molecular “signature” of ALS. The biomarkers will help with disease diagnosis and monitoring and also may provide new targets for experimental treatments.

Scientists at the MDA-supported ALS Therapy Development Institute are working to identify markers of disease progression in ALS.

Partnering with the ALS TDI to collect blood samples and, eventually, samples of muscle and fatty tissue for analysis are the MDA/ALS Centers at Methodist Neurological Institute in Houston; the University of California-Irvine in Orange, Calif.; and Mount Sinai Hospital and Medical Center in New York.

Several hundred blood samples have already arrived at the Institute and are being processed, and additional centers are expected to become part of the process.

The effort is part of a three-year, $18-million funding and scientific collaboration between the ALS TDI and MDA, through its Augie’s Quest initiative.

For information about blood or tissue donation, contact Beth Levine, senior associate scientist and project manager at the ALS TDI, at blevine@als.net or (617) 441-7200.

ALS to be a major focus in new MDA Clinical Research Network

MDA has committed $1 million per year in funding and selected 10 elite U.S. centers and clinics to become part of a new MDA Clinical Research Network. Five of the centers will work together to support trials and studies of ALS, and five will focus on Duchenne muscular dystrophy.

Disease-specific groups in the network will conduct projects and studies designed to enhance disease understanding. Goals include the development and implementation of studies that will lead to standardized clinical care; development of outcome measures to be used in clinical studies and trials; and development and testing of new treatments.

Centers will participate in large-scale activities, such as patient registries, and principal investigators (researchers) will participate in shared network projects and propose new projects.

The MDA/ALS centers, along with physicians who will be principal investigators, are California Pacific Medical Center in San Francisco, under Robert Miller; Columbia University in New York, under Hiroshi Mitsumoto; Emory University in Atlanta, under Jonathan Glass; Massachusetts General, under Merit Cudkowicz; and Methodist Hospital in Houston, under Stanley Appel.

Each center will receive $100,000 per year from MDA to cover infrastructure costs, and each will submit applications for grants from MDA and other agencies such as the National Institutes of Health (NIH).

Sangamo BioSciences to test compound that boosts VEGF A protein

Sangamo BioSciences of Richmond, Calif., has announced the opening of a trial of its experimental compound SB509 in adults with ALS who have adequate respiratory function, who have had ALS symptoms for fewer than three years, and who meet other study criteria. SB509 targets the gene for vascular endothelial growth factor A (VEGF A) and is designed to increase production of VEGF A protein. Laboratory studies have suggested this protein may protect and repair damaged nerve and muscle cells. The compound will be given by intramuscular injection. Contact Luci Barbi at the La Jolla, Calif., site at (858) 455-5463 or cns@cns.cts.com. Additional sites in California, Kansas and Maryland are expected to open soon.

A New Concept in ALS Care Facilities

by Bill Norman

Architect’s rendering of the Leonard Florence Center for Living in Chelsea, Mass. It will include the first dedicated ALS lodging and care facility of its type in the country.

A totally new type of care institution for people with ALS is being built in Massachusetts, and a man with ALS is helping design and raise funds for it.

“Before being diagnosed with ALS in October 2006, I had a great career, going on 13 years as a landscape architect,” writes Steve Saling, 40, of Andover, Mass., in his MySpace blog.

“Ironically, one of my areas of expertise was in complying with the Americans with Disabilities Act (ADA) to make sure public places were fully accessible to disabled persons."

Now Saling is putting his expertise to work on the Leonard Florence Center for Living (LFCL) on Admiral’s Hill in Chelsea, overlooking Boston Harbor. Groundbreaking on the center, which is being built under the auspices of Chelsea Jewish Nursing Home, took place in August. Estimated time for completion is 14 months.

The “Green House Project”

What’s so unusual about the LFCL, apart from being the first dedicated ALS facility of its type, is that it will be a “Green House” residence (a trademarked term), one of 10 in a 90,000-square-foot urban mid-rise condo facility.

Green House homes (not to be confused with environmentally “green”) are dramatically positive departures from stereotypical assisted living facilities and nursing homes. Scores of them, designed to accommodate the elderly, now exist across the country.

A 2001 study by the Institute of Medicine found that assisted living facilities often are characterized by problems with bedsores, malnutrition, infections, loss of activity in daily living functions, improper medication use, high levels of depression and poor quality of life. Judith Rabig, former executive director, of the national Green House Project, in 2005 told the White House Conference on Aging, “moving to a nursing home is a dreaded event.”

By contrast, the Green House model was created to provide a home where people live in intentional communities with competent, consistent, well-trained caregivers, and are restored to lives “rich in autonomy, dignity and choice … where priority is given to their quality of life,” Rabig said.

“Eden Alternative” origins

From left, Steve Saling, landscape architect; Barry Berman, executive director; and Adam Berman, director of business development, at the LFCL construction site.

The Green House concept is based on the Eden Alternative, a nonprofit organization created in 1991 by William Thomas, a physician and geriatrician. Eden Alternative is “dedicated to eliminating the plagues of loneliness, helplessness and boredom that make life intolerable in most of today’s longterm care facilities,” says its Web site (www.edenalt.org).

Adapting this concept designed for the elderly, Saling and Barry Berman, executive director of Chelsea Jewish Nursing Home, teamed up and created plans for a facility uniquely suited to the needs of people with ALS.

“For me, this meant taking 31 years of experience with nursing homes and creating something dramatically different,” Berman said. “It’s been an incredible experience; we’ve all come to realize the time has come for a completely different model of care.”

An array of aids, comforts

The ALS home in the LFCL will accommodate 10 people with ALS.They’ll each have private, accessible bedrooms and bathrooms; dine family-style on home-cooked food they can order from the in-home kitchen as they wish; socialize in a central gathering room with a fireplace; and enjoy outside courtyards with lush vegetation.

The project is collaborating with the Assistive Technology Program at the University of Massachusetts in Lowell. Each ALS resident will have a technology package custom designed for his/her use by a senior engineering student, under the supervision of a professor.

Saling enumerated the assistive technology that will be available:

• Computer “command centers” on wheelchairs (usable by hand or eye controls, as appropriate) will regulate climate controls in rooms, open and close doors, call for the elevator, order a drink or snack from the kitchen or send a text message to attendants.
• Each bedroom/bath will have a ceiling track lift system.
• Oxygen will be available in each room.
• “Most importantly,” Saling said, “When necessary to go on a vent, you won’t get kicked out. All 10 rooms will have vent support.”

Enter the “shahbazim”

Thomas, creator of Eden Alternative, coined the term “shahbaz” (plural “shahbazim”) to describe caregivers. It comes from a Persian word that translates as “royal falcon.” “Its quality of mystery is what makes it well chosen to define a new concept,” he says in his blog (http://shahbazim.blogspot.com).

In the Green House concept of caregiving, shahbazim will be devoted to the arts of homemaking and lovingly prepared meals. They will operate in addition to a clinical support team that includes nurses, social workers, therapists, medical directors, nutritionists and pharmacists, who will visit the house regularly to provide services as needed.

Saling says the center’s ALS facility is unique in this country, and possibly the world: “There are places that may accept an ALS patient, but you are just that, a patient. If unvented, a [person with ALS] might live in an assisted living facility, as I am now, or a nursing home. The problem there is that I’m 40 years old; the next youngest resident is twice my age. The thought of living the rest of my life [in a standard long-term care facility] is not very appealing.”

Saling notes that some states only have one or two facilities that will accept a patient on a ventilator; some states have no such facilities at all.

Of the ALS Green House residence he says, “There really is no comparison to anything other than your own home, and then only if you happen to be a techno-geek.”

Covering the costs

Vigorous fundraising is financing the basic structure of the LFCL and all ALS-specific equipment. Saling and Berman are highly optimistic they will meet their goal.

Berman said he expects that most, if not all of the people with ALS who move in to the facility will be enrolled in Medicaid, which will help defray some of their daily living costs.

Perhaps the largest problem right now is how to select the 10 residents for the new facility. Berman says he already has received hundreds of applications — including one from Saling — and some from other countries.

“It’s a very emotional project for me. Our selection really needs to be geared to the ALS individual who wants to continue to lead an active life and take advantage of technology. The center can’t be for someone who just wants to stay in bed.”

Planning for more

When completed, the new-concept care facility will accommodate 10 residents with ALS.

Help could be on the way, thanks again to Steve Saling, accomplished architect in more ways than one. He, his family in Georgia and a coalition of elected officials, educators and health care industry experts are taking a different but complementary tack to building another ALS-specific care facility in that state.

“With the experience I gain in Massachusetts and Georgia, I would like to initiate similar projects in other states,” Saling said.

“It is my hope to make life on a vent look more attractive than death, and thereby increase the paltry five percent of us that choose to live when the necessity to vent arrives.”

The ‘EYES’ Have It
Eye-control technology puts you back in the conversation

by Alyssa Quintero

Eye-controlled devices, commonly referred to as eye-tracking or eyegaze systems, enable users to access speech-generating devices and computers. Eye control isn’t without its challenges, but many with ALS say the technology has changed their lives, providing greater independence and allowing them to live better.

In recent years, eye-control technology has evolved, resulting in systems that are faster, more accurate, smaller and more portable, highly customizable, more cost-effective, and typically able to be calibrated in 30 seconds or less.

The June ALSN article “A Complete Communication Solution” discussed dynamic display (large touch screen) alternative augmentative communication (AAC) devices with multiple access methods, which also serve as fully functioning Windows XP computers.

Eye-controlled systems open these speech-generating computers to users with little or no movement. Most systems can be mounted to wheelchairs, floors, desks, tables, beds, etc. Here’s a look at what users are saying, all with their eyes.

‘I love you’

Terry Sickels of Akron, Ohio, received an ALS diagnosis in late 2005. When he started experiencing speech problems last year, Sickels, 58, tried several AAC devices, but none worked very well for him.

Sickels’ wife, Tammy, researched other options and discovered eyecontroltechnology and the MyTobii P10, manufactured by Tobii Technology Inc. in Sweden, and distributed in the United States by Tobii Assistive Technology Inc. (Tobii ATI). From the start, it worked well for him.

Sickels uses the dwell selection method in which he focuses steadily on a certain part of the screen for an adjustable period of time before the device makes the selection.

“The most consistent movement I have is my eyes, and this is the only unit that accommodates that without recalibrating all the time,” Sickels wrote via e-mail.

He uses the device for text-to-speech, as well as Internet, e-mail, text messaging and environmental controls such as the television remote. Sickels also uses buttons programmed with greetings, questions, yes/no answers, and other generic sayings. Customizing the system with phrases, names and topics has made it more personal and easier to have conversations.

Terry Sickels, who once used an alphabet board to communicate, amazes grandsons, Joey and Christopher, with his ability to look at buttons that speak various messages, including some jokes.

Sickels has difficulty using the system’s onscreen keyboard but is improving with practice. Currently he can type about 10 to 15 words per minute. The premade text boxes work well in the meantime.

“We’re not speculating what he’s trying to say anymore,” Tammy says. “He’s more relaxed, and he’s got that little spark in his eyes again. He’s laughing more, and it seems like he’s having fun because he has some freedom, and he’s more in control.”

Sickels now can tell doctors and therapists how he’s feeling or if he’s experiencing pain. Prior to appointments, Sickels creates text buttons that ask questions for him.

Because he tends to lock on message buttons when he doesn’t mean to say anything, Sickels and his caregiver created an onscreen “rest” button that he can click with his eyes to go to a “blank” page. A “return” button allows him to go back to the previous page when he’s ready to resume speaking.

After using the device less than a month, Sickels surprised Tammy on her birthday by programming buttons that said: “Happy 50th Birthday,” “I have a present for you,” and “I love you."

“It was more personal for the words to come from me as opposed to having someone else say it for me,” Sickels writes.

“I’m tired of people treating me like I’m not in the room. This device allows me to voice my opinion, offer suggestions and show people that I’m the same person I was before. People have started to talk to me and ask me questions.”

ERICA speaks

Don Taylor of Collierville, Tenn., has used Eye Response Technologies’ ERICA system since June 2007, and writes via e-mail that the learning curve wasn’t very steep because he’d been using onscreen keyboards with word prediction through the EZ Keys software prior to ERICA.

“I have over 22 years of computer experience, and I demand my computer system to be well integrated so I can do all the things that I could do before I became disabled,” Taylor, 51, wrote via e-mail.

“I don’t want to be slowed down by a system that offers scanning or Morse code. And, ERICA runs on a Windows platform, so I can run the same applications that I ran on my desktop computer.”

Taylor, who spends most of his time on the Internet, began typing with his eyes immediately after the initial setup. He maintains a blog and serves as the Webmaster for his son’s Boy Scout troop. He credits ERICA’s tech support and software upgrades with helping him stay on track.

He adds, however, that every time he turns off or moves away from the system, he has to recalibrate, which he can do without assistance.

“What I like best is the way the makers of ERICA designed the software to allow me to do everything with my eyes that I would do if I could type with a keyboard,” Taylor says.

While he recommends the system to others with ALS, he wouldn’t suggest it for people who don’t have any experience with a Windows-based computer because “it’s not stable enough and requires maintenance, including virus protection, Windows updates, data backups, etc.”

One drawback for Taylor is that the camera is fragile; he says the system would be more versatile if the camera were built into the system (it sits under the screen). And, he cautions that moving ERICA onto the wheelchair mount from the floor mount is difficult.

"No computer system is without flaws,” Taylor notes, urging potential buyers to “talk with a user in addition to the salesmen.”

To learn more about Taylor’s experiences with ERICA, visit his blog (http://alsdon.blogspot.com).

It’s going to cost …

Don Taylor (with family friend Ryan Waltman) spends much of the day using his ERICA for generating speech, as well as staying online.

While eye-controlled communication devices sound like a great solution, many speech-language pathologists and AAC specialists caution that what works for one person may not be the ideal solution for another.

To learn more, contact the manufacturers, as they may be able to put you in touch with users who have ALS. Of course, each manufacturer asserts that its system and camera is faster, more accurate, easy to calibrate, has better IR sensors and mounting solutions, etc. But since eye-controlled systems are pricey, in the end it’s advisable to “try before you buy.”

Start by working with the speech therapist at the local MDA clinic, and check with the local MDA loan closet to try loaner devices. In addition, most manufacturers have rental or loan programs; in some cases, rental costs can be applied to the purchase price.

These programs also are helpful if someone needs a loaner device for an extended period such as while waiting for insurance approvals or lengthy delivery times.

Dedicated AAC systems with eye-control options typically range in price from approximately $6,800 to $15,000. The cost increases with additional hardware and software options. (See “Eye Technology Manufacturers.”)

Medicare will cover up to 80 percent of the cost for an AAC device, and MDA offers a one-time $2,000 grant for devices prescribed through its clinics. MDA also will provide $500 annually for repairs and modifications.

Baby, It’s Cold Outside!

by Amy Labbe

When it comes to cold weather and ALS, 53-year-old Pati Milewski, of Olympia, Wash., likens her experience to that of “a house with no thermostat.”

Although inability to regulate body temperature isn’t recognized as a classic symptom of ALS, decreased mobility limits the ability to stay warm by being active.

Simply feeling cold is only part of the problem. “Cold weather exaggerates the problems that come with ALS. It increases the effects, making stiffness worse and weakness more intense,” says Daryl Thorson, 72, of Brandon, S.D. Thorson received an ALS diagnosis in 2005.

To keep shiver-inducing temperatures from getting the best of you, check out the following tips, including — and especially — the nitty gritty details.

Warmth-generating habits

There are plenty of little things a person can do to generate warmth in their daily routine.

Some of these include:

• Stretching, range-of-motion (ROM) exercises and massage to increase blood flow;
• drinking warm beverages;
• leaving warm water in the tub after bathing to increase humidity and ambient air temperature;
• placing dark rugs in areas of the house where they can absorb heat from the sun;
• leaving the oven door open after cooking;
• staying well-nourished and hydrated; and
• avoiding sweating or getting skin wet in cold weather, protecting skin from the wind, and wearing mittens instead of gloves to more effectively hold heat.

Milewski, who received an ALS diagnosis in 1999, suggests that those using feeding tubes fill the “kangaroo bag” with warm or hot water when hydrating. If you prefer cold water, she adds, put a dry hand towel around the feeding tube under your shirt.

Body-warming gadgets and blankets

A multitude of products provide warmth to fingers, toes, and everything in between.

Standard hot water bottles, available at any drugstore, are useful for keeping your hands and lap warm, or for toasting your tootsies in bed. (Be sure to fill bottles with water hot enough to warm, but cool enough that it won’t burn should it spill.) For more portable heat options, try socks or fabric bags filled with uncooked rice or beans. Microwave until warm, then soak up the heat.

Hand warmers commonly used in outdoor sports or for heat therapy can be air-activated (typically disposable) or activated through snapping a small metal tab that causes crystallization of a solution. This second type often can be recharged through microwaving or boiling. A third type of warmer works through the use of lighter fluid.

Warmers for hands, toes, feet and the entire body can be found at outdoors and sports-themed stores, along with heated socks, heated headbands to keep ears warm, hand muffs, and sleeping bag warmers to heat up your bed before you get in it.

In addition to common electric blankets (available most places blankets are sold), try the super-warm sleeved fleece blanket known as the Slanket (www.theslanket.com). Or zip and snap to create sleeves and a closer fit with a Biederlack CuddleWrap (301-759-3633, www2.biederlack.com).

Also, a quick Web search or visit to most outdoors-themed stores will turn up a variety of 12-volt heated travel blankets designed to draw power from your vehicle’s power outlet and keep you toasty warm when traveling.

Caution: To avoid the risk of possible burns, always make sure you’re able to remove electrical blankets and other heat products on your own or that someone remains nearby to assist you should they become too hot.

Clothing — all fabrics are not created equal

Milewski wears long underwear, or “long johns,” yearround and white cotton gloves in bed when she’s cold. She also wears layers of clothing and a hat and gloves when she goes out. Thorson also wears layers indoors.

Note: There’s more to layering for warmth than meets the eye.

The idea behind layering isn’t simply to put clothes on top of more clothes. For maximum effect, the layer nearest skin should wick away moisture, the mid layer should provide warmth and the outer “breathable” layer should keep wind and water out.

Wicking fabrics, most of which are some type of polyester, keep you dry by transporting moisture and the cooling effects of evaporation away from the body.

Fabrics such as wool and fleeces, used as middle warmth layers, trap warm air while wicking away moisture. They’re lightweight and dry easily, but lack durability and need a protective shell.

Outer layers should keep out wind and water. In additionto ordinary lightweight windbreaker-type jackets, more breathable fabrics include GORE-TEX and Cordura.

Indoors or out, whether it’s cold or you just feel that way, put these warmth-generating ideas to work for a difference you can feel.