ALS Research Roundup

Why wait for the next ALS Newsmagazine? Receive monthly e-mail summaries of breaking research news directly in your inbox. Go to www.mda.org/QuestMagazineOnline and click "Get monthly summaries of Quest Extra stories."

Trial of SOD1 blocker set to open soon

A phase 1 clinical trial of the experimental drug ISIS-SOD1-Rx (formerly ISIS-333611) in patients with the SOD1-related type of familial (inherited) ALS is expected to begin before the end of 2009 at Washington University in St. Louis and Massachusetts General Hospital in Boston. Eventually the trial will include four additional sites.

MDA provided support to Timothy Miller at Washington University in St. Louis to work with Isis Pharmaceuticals of Carlsbad, Calif., to develop ISIS-SOD1-Rx.

The trial will test the safety and tolerability of this “antisense” compound, which is designed to block production of the SOD1 protein in people who have developed ALS because of mutations in the SOD1 gene. Such mutations result in ALS in approximately 1 percent to 3 percent of cases.

The investigators will infuse ISIS-SOD1-Rx into the fluid that surrounds the brain and spinal cord, a delivery method that targets the cells that produce the toxic SOD1 protein.

Details of genetic testing will be discussed with potential study participants. For further information as it becomes available, see the clinical trials section of the MDA Web site by going to www.mda.org and selecting Clinical Trials from the home page.

Masking Unwanted Instructions with ‘Antisense’
	Antisense strands will be infused into the fluid surrounding the brain and spinal cord, where it is hoped they will stick to the flawed strands of RNA. There they are expected to block the RNA instructions that would otherwise result in ALS-causing superoxide dismutase 1 (SOD1) protein molecules. (When cells process a genetic recipe for a protein, they first convert DNA to RNA.)

One lithium study stopped; MDA study continues for now

The investigators for one study of lithium carbonate in ALS announced Sept. 23, 2009, that they will stop their study after an interim analysis showed the drug was not beneficial. The study was funded by the National Institutes of Health, the ALS Association and the ALS Society of Canada; MDA was not a funder of this study.

As of October 2009, an MDA-supported study of lithium remains open. The MDA trial is separate from the canceled NIH trial, and the dosages and trial design are not the same.

Clinical trials of the effectiveness of lithium in ALS were undertaken after a small study in Italy was published in 2008, reporting that lithium appeared to dramatically slow the course of the disease.

However, recently published results of a study of lithium in ALS mice conducted at the MDA-supported ALS Therapy Development Institute in Cambridge, Mass., showed the drug lacked  benefit on any measure.

The study was published online Aug. 3, 2009, in PLoS One.

Merit Cudkowicz, who directs the MDA/ALS Center at Massachusetts General Hospital in Boston, was an investigator on the NIH-supported study.

First U.S. trial of neural stem cells in ALS gets FDA green light

The U.S. Food and Drug Administration (FDA) has given a green light to a phase 1 trial to study the effects of injecting human neural stem cells into the spinal cords of people with ALS, the biotechnology company Neuralstem announced Sept. 21, 2009.

Neuralstem of Rockville, Md., will sponsor the study, which, if approved by an institutional review board at Emory University in Atlanta, will take place at that site. No participants will be recruited until Emory’s review board approves the study.

Neuralstem’s patented stem cells have the ability to develop into motor neurons and a type of support cell known as glia.

Jonathan Glass, neurologist and director of the MDA/ALS Center at Emory, is the onsite principal investigator, with Eva Feldman at the University of Michigan serving as the overall principal investigator. Emory neurosurgeon Nicholas Boulis, a pioneer in developing surgical methods for delivery of therapeutics to the spinal cord, will perform the surgical procedures at Emory.

“This is the first time in the United States that cells will be injected into a human spinal cord, although these cells have been tested in several models of spinal cord injury in rats,” Glass said.

Neuralstem’s patented stem cells, developed from cultured neural stem cells derived from a single fetus, have the ability to mature into various types of cells in the nervous system. This includes motor neurons, the muscle-controlling nerve cells that are specifically lost in ALS, and nervous system support cells known as glia.

“This study will be focused on the safety of the procedure for introducing stem cells for the treatment of ALS,” Glass said of the phase 1 trial. “Our hope is to find a surgical approach that is manageable in humans with no negative effects. As with any phase 1 clinical trial, a patient may benefit from treatment, but that is not the focus of this study.”

The proposed study would include 18 ALS patients and, if approved, recruitment is expected to begin by the end of 2009.

“We are very excited about the possibilities this study may bring,” said Glass, “and are hopeful this is the first step toward a new way of treating ALS.”

Details of the proposed trial, including selection of participants, will be posted as they become available on an Emory Web site at www.neurology.emory.edu/ALS and on MDA’s Web site at www.mda.org (click on Clinical Trials).

New type of ALS research mouse now available

Mice carrying a mutation in the gene for the TDP43 protein that’s known to cause ALS in humans have been developed by MDA-supported scientists at Washington University School of Medicine in St. Louis. The mice may provide an important new research tool in this deadly disease.

Iga Wegorzewska and colleagues published their findings online the week of Oct. 12, 2009, in Proceedings of the National Academy of Sciences. MDA grantee Robert Baloh coordinated the research team.

Until now, most ALS research not conducted in humans has utilized mice with various mutations in the SOD1 protein, which also cause human ALS. However, since mutations in any particular gene only cause a small percentage of human ALS cases, the availability of a new “mouse model” of the disease is expected to broaden scientists’ ability to observe disease progression and the effects of experimental treatments.

Mice carrying the TDP43 gene mutation develop a disease resembling human ALS. They appear normal up to about 3 months of age, after which they develop a gait abnormality. By about 4.5 months, the mice with the TDP43 mutation begin losing weight and develop a “swimming” type of locomotion, dragging their bellies on the ground and using their limbs to propel them. Their average survival time is 154 days, or about five months. Normally, mice live about two years.

Three new DNA variants ID’d that may raise ALS risk

A large, multinational study to identify genetic risk factors associated with ALS has found two DNA sequences on chromosomes 9 and one on chromosome 19 that are significantly different in people with ALS compared to those without the disease.

The identified DNA regions on both chromosomes contain genes for biological processes that could have an effect on the disease. Gene variations in the chromosome-9 region have been associated with ALS in combination with the cognitive disorder frontotemporal dementia.

For the first time, a specific DNA variant on chromosome 19 was identified as having a possible ALS association. The investigators say the variant is in the same DNA region as a gene that helps regulate transmission of signals between nerve cells and between nerve and muscle fibers.

Leonard van den Berg and Roel Ophoff at the University Medical Center Utrecht in the Netherlands coordinated the study team, which published its findings online Sept. 6, 2009, in Nature Genetics. MDA supported Simon Cronin and Orla Hardiman at the Royal College of Surgeons in Ireland for portions of the study.

The new findings represent the latest in a series of “whole-genome” (all genes in a person’s makeup) association studies, also known as “genome-wide” association studies. This type of study looks for small variants in DNA sequences that are significantly more common in people with ALS, although the strategy is still in development. (See “How Reliable are Genetic Association Studies?” in the September-October 2009 ALS Newsmagazine.)

This latest study included an analysis of all the DNA from an initial group of 2,323 people with ALS and 9,013 unaffected people, followed by further investigation of potentially significant findings in another group of 2,532 ALS patients and 5,940 people without the disease. The study subjects were from the United States, the Netherlands, Ireland, Sweden, Belgium, the United Kingdom, France, Poland and Germany.

A surprise discovery in the new study is the association of a variant in a gene known as UNC13A on chromosome 19 that’s more common in people with sporadic ALS than in unaffected subjects. Since the UNC13A protein made from the gene is known to play a role in the transmission of signals among nerve cells and nerve-to-muscle signals, its influence on ALS development seems like a potentially productive research lead.

Also surprising and potentially valuable was the discovery that genetic variants on chromosome 9 that are known to be linked to a form of familial ALS accompanied by dementia also may be linked to sporadic ALS. The investigators found two specific variants in this region that are significantly more common in sporadic ALS patients.

Among earlier whole-genome association studies conducted in ALS are an MDA-supported study by the Phoenix-based Translational Genomics Institute (TGen) and another by the U.S. National Institutes of Health (NIH) in Bethesda, Md.

The TGen study suggested genes associated with the connections between nerve and muscle fibers might be different in people with and without ALS. However, critics charged the statistical methods used in this study might not have identified true differences between the two groups. The NIH study investigators found no significant differences between ALS and non-ALS genomes.

The differing results from the multiple whole-genome association studies in ALS have led to the conclusion that there may be no single “smoking gun” to be identified from this type of analysis. Study results support the idea that ALS is not one but many diseases, with differing combinations of causal factors. This understanding and the leads provided by the findings from each study are important for investigators to take into account as they work to develop treatments.

Athena Diagnostics offers new group of DNA tests for FALS

A new test panel that may detect up to 35 percent of the genetic flaws that can cause familial ALS (FALS, an inherited form of the disease) has been released by Athena Diagnostics (www.athenadiagnostics.com) of Worcester, Mass. Athena is a commercial laboratory specializing in DNA testing for neurological disorders.

The panel tests for mutations in the SOD1 gene, FUS gene, TDP43 gene (also known as the TARDBP gene), angiogenin gene and FIG4 gene. Each test, except the FIG4 test, also can be performed individually.

A blood sample, which can be drawn locally and shipped to Athena, is required. For details, contact Athena at (800) 394-4493 or through the company’s Web site.

ALS TDI research symposium posted online as webcast

A webcast is now available of the fourth annual research symposium held as part of the ALS TDI Leadership Summit 2009 on Oct. 5. The symposium was conducted at the MDA-supported ALS Therapy Development Institute in Cambridge, Mass.

The webcast of the symposium, an update on research in ALS, is free but requires registering via the Web site. Go to www.als.net/summit.

Putting a Block on a Muscle Blocker

Scientists look into targeting muscle instead of nerve in an effort to stave off muscle degeneration in ALS

by Amy Labbe

Several recent studies by MDA-supported researchers have furthered interest in the possible benefits of targeting muscle instead of nerve tissue as a means to slow loss of strength in people with ALS, traditionally considered a nervous system disease.

One potential muscle-targeting therapeutic strategy involves manipulating or blocking a protein in the body called myostatin, which normally limits muscle growth. The strategy also is being investigated in muscle diseases.

Although “myostatin blockade” doesn’t appear to influence survival in mice with a disease resembling ALS, it has been shown to improve muscle size and strength, even as motor neurons, which send signals to muscle and fail in ALS, continue to be lost.

Such effects could contribute to improved quality of life for people with ALS.

Normal	ALS
In ALS, the motor neurons, which normally send signals to muscle fibers via a neuro-transmitter called acetylcholine, degenerate. As motor neurons fail, their fibers retract, and signaling to muscle fibers is disrupted. Most ALS therapies in development target the motor neurons or other cells in the nervous system. Myostatin blocking targets the muscle fibers, with the goal of maintaining strength and function even as nerve cells fail.

Member of a family of growth-regulating hormones

Myostatin belongs to the transforming growth factor-beta (TGF-beta) family of proteins involved in the normal development of muscles. Its role is to inhibit muscle-fiber growth and regeneration, and scientists are working to understand precisely how it does its job so that they can devise ways to interfere with or stop it. 

Structural biologist and MDA grantee Tom Thompson at the University of Cincinnati, and colleagues, recently characterized the structure of the myostatin protein at the atomic level, something Thompson hopes will allow the academic community and the pharmaceutical industry “to make use of the information in their efforts to design myostatin inhibitors.”

The investigators published their results in the  Sept. 2, 2009, issue of the European Molecular Biology Organization (EMBO) Journal.

Prior to the study, the specific structure of myostatin was unknown, Thompson says. “We understood that it was part of this family of proteins that looked similar, but we didn’t have the details. From this work we were able, for the first time, to pick out key details of what myostatin looks like.”

Thompson explains that knowing the protein’s structure offers clues as to how it works and functions in the body, and says he believes it “will make the jobs of companies putting effort into myostatin therapy a lot easier.”

Blocking a blocker

“There is an extensive effort being directed at developing drugs capable of blocking myostatin signaling,” says Se-Jin Lee, a geneticist and MDA grantee at Johns Hopkins University School of Medicine in Baltimore.

In 1997, Lee created a strain of mice lacking the gene for the myostatin protein and showed that they developed more muscle and greater strength than mice with normal myostatin genes. “Most of this effort has focused on biologics capable of binding [sticking to] myostatin and inhibiting its activity,” he says.
One method to block myostatin involves using neutralizing antibodies (immune system proteins) that stick to myostatin and interfere with its signaling actions.

Wyeth Pharmaceuticals of Madison, N.J., developed such a compound, called MYO-029, and, with supplemental funding to trial sites from MDA, tested it beginning in 2005 in adults with muscular dystrophy.

Although investigators found the compound was safe and well tolerated, the study was not designed to assess muscle strength and function, and the company announced in March 2008 that it would not continue development of MYO-029 for muscular dystrophy.

In a second approach to myostatin blockade, a mutated propeptide (or “precursor,” an immature form of the myostatin protein) inhibits myostatin by binding to it and forming an inactive complex that is unable to stick to its receptor. (A receptor is a protein molecule that prompts signaling when docked with its partner.)

Amgen, a biotechnology company headquartered in Thousand Oaks, Calif., has completed healthy volunteer studies for its myostatin inhibitor, AMG745, under development to treat muscle disorders. 

A third strategy achieves blockade through inhibition of the normal binding of myostatin with its usual receptor, activin receptor type 2B. A nonfunctional, partial molecule that contains a portion of the usual receptor is introduced. This “decoy” receptor sticks to myostatin, effectively keeping it away from its regular, functional receptors.

“The myostatin will bind to these decoy receptors similarly to how it would bind to its natural receptor,” but without all the components of its natural binding partner it’s unable to send signals, says MDA grantee Kathryn Wagner, who is director of the Center for Genetic Muscle Diseases at the Kennedy Krieger Institute in Baltimore and co-director of the MDA Clinic at Johns Hopkins University in that city. “Essentially, it sops up the myostatin and stops it from signaling.”

On Sept. 10, 2009, biopharmaceutical company Acceleron Pharma of Cambridge, Mass., released phase 1 clinical trial results on its soluble receptor ACE031, developed to treat loss of muscle mass and function. 

“Acceleron’s data showed increased lean body mass and increased muscle size in healthy volunteers receiving a single dose of the soluble receptor,” says Lee. “These results are very exciting, as this is the first clear indication that this general strategy may work in humans.”

More, stronger muscles in ALS mouse model

Wagner and MDA grantee Brett Morrison of Johns Hopkins, and colleagues, published study results on a “mouse version” of Acceleron’s ACE031 in the June 2009 issue of Experimental Neurology.

The investigators described studies in which mice with an ALS-like disease were treated with a soluble activin receptor type 2B. These mice experienced delay in the onset of weakness, increased body weight and improved grip strength in tests where treatment began before symptom onset and also in tests where treatment was initiated after symptoms began.

Treatment with the decoy receptor did not increase length of survival.

“The remaining muscle fibers are probably stronger, and therefore allow the animal to compensate while the loss of motor neurons continues,” Wagner explains, noting that evidence for this is the lack of increased survival time in the treated mice. “So because the remaining motor units [the motor neurons and the muscle fibers to which they send signals] are larger and stronger, there’s a longer time before significant weakness occurs in the mouse. We hope that would translate to a longer time before significant disability in humans.”

If the remaining muscle is stronger, then people with ALS and other progressive muscle diseases might be able to manage the activities of daily living longer, increasing their quality of life, Wagner adds, “by making them stronger while they have the disease.”

Although the study looked at SOD1 mice, engineered to model a familial form of the disease caused by a mutation in the superoxide dismutase 1 gene, this type of treatment wouldn’t be specific to the SOD1 form of ALS.

“Quite the opposite,” Wagner says. “It’s a common strategy that we’re looking at now in both muscular dystrophy and ALS. We’re not influencing the underlying pathophysiology, we’re just making more, stronger muscles.”

Working toward cures and treatments simultaneously

“Many researchers in ALS are working toward a cure,” Morrison acknowledges. “But it is our hope that treatments that improve atrophy and weakness could be available right now to provide functional benefits in patients and improve quality of life for years.”

He notes that such treatments may allow people with ALS to avoid a wheelchair, continue to feed themselves or maintain enough strength to speak without assistance, for additional months or, possibly, years.

MDA researchers continue to home in on refining the ways in which myostatin and the TGF-beta signaling pathway might be targeted to help those with muscle atrophy and weakness, as well as how such strategies may be combined with the addition of neurotrophic (muscle-nourishing) factors, such as insulin-like growth factor 1 (IGF1), and exercise.

Caring for caregivers, too

by Amy Labbe

November is National Family Caregivers Month, and MDA wants to remind those who are caring for someone with ALS that you’re not alone. We’re here to help.

When you have questions or need help, when you want to share tips and tricks or opinions, or when you just need to hear from someone who’s “been there,” one of the first places you can turn is an MDA ALS support group.

Although these groups vary widely in the way they’re organized and scheduled, they all have one thing in common: They provide essential support for both people with ALS and their caregivers that makes a significant difference in learning to live with ALS.

’I was nervous’

Larry and Linda Martin of Spring, Texas, attend an MDA ALS support group at Memorial City Hospital in Houston, where they meet for two hours the second Saturday of every month (July excluded).

Larry, 68, received an ALS diagnosis in November 2007. He’s lost the use of his left hand, experiences weakness in his legs, and has balance and breathing difficulties.

Larry Martin, who has ALS, and his wife and caregiver, Linda, both get something out of MDA ALS support groups.

The couple married in 1962 and, although she receives help from their son, Scott, and a group of neighborhood friends, Linda, 67, is Larry’s sole caregiver.

“So far we have been able to handle everything without professional help,” Linda says, noting that, as Larry’s caregiver, she assists him with almost everything, including getting out of bed, showering, shaving, brushing his teeth, dressing, eating, toileting, and getting in and out of chairs and vehicles. She also assists him on the computer, does all the driving, helps him get ready for bed, adjusts his pillow and covers, and works with him to do range-of-motion exercises to help his shoulders.

“The physical part for me hasn’t been bad yet, but as time progresses I can see it being a problem,” Linda admits. “Emotionally, I think the name of the game when dealing with ALS is being able to adapt. We don’t make a big deal out of another loss — we just figure out a way to get around it as best we can.”

Linda notes that Larry is “a very easy patient to deal with” and that he’s “very thoughtful” of her, but that “the hardest part for me is knowing the frustration he feels at not being able to care for himself and having to have help with everything.”

The two have been attending support group meetings for approximately 18 months.

“I was nervous about going,” Linda says, “because I was afraid it would be a very depressing experience. I found out quickly that was not the case.”

Come out with a smile

At the MDA support group the Martins attend, individuals with ALS and caregivers stay together for the first hour to listen to a speaker or ALS-related presentation. MDA Health Care Service Coordinator Clara Utley “always asks if there are certain topics we would like to see addressed or speakers we would like to hear, and she gets everything lined up,” says Linda.

Meeting topics have included home renovations, Social Security benefits, physical and occupational therapists, clinical trials, research, tax advice, home health care and hospice.

During the second hour, the group splits up, with caregivers meeting in a separate room with Rebecca Axline, a social worker from Methodist Hospital. Linda says this portion of the meeting “is great for me. I get a lot of useful information from other caregivers. We’re free to discuss anything we have on our minds.”

Subjects include creative ways of taking care of loved ones, gadgets that work or don’t work, or strategies that make the caregiving process easier or more efficient.

One example, Linda notes, is “someone suggested using a wireless doorbell as a call button. It was simple, inexpensive and easy to use, and solved the problem. When I hear the doorbell, which rings differently from our regular doorbell, I know Larry needs me for something.”

Other topics include trips others took, with descriptions of things that were particularly easy or difficult, as well as any surprises they encountered and tips to get around easier.

“Sometimes we talk about funny stuff that happened since we met last time,” Linda says. “If someone has been recently diagnosed we can give them a place to ask questions and let them know others care.”

Other times, Linda adds, “you might just want to know if other caregivers have the same frustrations or feelings you do.”

Linda says that even when she doesn’t actively participate in the discussions, she learns a lot just by listening and that she always “gets something” out of each meeting.
And after those two hours, she says, “I usually come out with a smile on my face.”

Educational and supportive

Clinical social worker Rebecca Axline characterizes the first portion of the meeting as “educational” and the second as “supportive.”

“The number of attendees varies greatly depending on the topic and the current health status of the local MDA ALS patients,” Axline says, noting they’ve had “as few as six and as many as 30, with an average attendance of 12 to 14.”

Although typically half of those who attend are people with ALS, and half are their caregivers/loved ones, some individuals bring large numbers of family members along.

The general aim is to provide education in a comfortable, informational setting first, and then to provide an opportunity for emotional issues, questions and concerns to be shared within a safe, private and confidential setting with trained social work facilitators, Axline says. “We feel this allows for individuals to find support, ask questions, and express themselves without worrying about their loved ones’ feelings.”

The benefits to be gained by caregivers who attend these meetings are many, and include:

• exploration of thoughts, feelings and emotions in a supportive environment;
• networking with others;
• mutual support among group members; and
• the awareness that “I’m not alone.”

A sense of connection

One of the most important things ALS support groups provide caregivers may be the understanding that there’s help out there and that caring for someone who has ALS isn’t something you have to do alone.

“When we first suspected Larry had ALS,” Linda Martin says, “we knew nothing about the disease except that a baseball player had died from it and they made a movie about it. We had no idea what questions to ask or, if we thought of a question, who to ask. MDA ALS support groups helped change all that. Just being with families going through the same thing you are helps a lot.”

Linda recommends MDA ALS support group meetings to other ALS caregivers she meets.

“I tell them to just give it a try once or twice. There is a lot of useful information there. If it’s not your thing, you don’t have to come back, but you’ll probably benefit, and it would be a shame not to use every resource available to you.

“Larry and I both look forward to the meetings. It has been great for us — we always come out feeling like we just got our batteries recharged.”

For information about MDA ALS support groups in your area, call your local MDA office at (800) 572-1717.

It’s their way and the highway

by Bill Norman

Name almost any scenic part of America with decent roads, and chances are good it’s been visited by someone with ALS in a motor home (RV).

Far from being a barrier, having ALS — at least in the case of these three families — has been the motivation to hit the road in a big self-contained motorized rig and see the country.

The Melott family of Ranchos Palos Verdes, Calif., has always loved the outdoors, and that didn’t change when Jackie learned in August 2006 that she had ALS. Today the family (husband Tim, children ages 20, 16 and 13, and the family dog) are out in their RV nearly a month of every year. They usually take along a caregiver.

Works as an antidepressant

Jackie, 51, has severe mobility impairments, uses a power wheelchair and is vented full time via a tracheostomy. At home she sometimes gets depressed. Tim says he knows then that it’s time to fire up their 34-foot diesel-powered RV and head for the country. “She visibly perks up, almost as soon as we’re out of the driveway,” he says.

Tim modified their motor home by replacing a window behind the passenger’s seat with a 36-inch-wide doorway. To get Jackie and her wheelchair up and inside, they use a Superarm motorized lift with 600-pound capacity.

Their RV sometimes tows a trailer with four ATVs (all-terrain recreational vehicles).  Other times they tow a rented accessible van for transporting Jackie when the RV is parked. They often link up with friends who meet them in the boondocks and stay in their own RVs or simply pitch tents around a campfire. The Melotts prefer to “dry camp” away from organized RV parks and campgrounds so they can run their ATVs. Their motor home travels have taken them throughout California.

One-drawer ‘modification’

Betty Surtees, 73, received an ALS diagnosis in November 2006. Her assistive equipment includes a bilevel positive-airway-pressure respirator (BiPAP), cough assist, suction machine and feeding tube.  “I have a machine that can talk for me, but so far I prefer to use the dry-erase board for communication,” she says via e-mail.

Surtees, who has bulbar-onset ALS, is ambulatory if she’s careful (last year she fell and broke her hip), so their 36-foot motor home hasn’t had to be modified yet — except, she notes, “one drawer is lost to clothes as it now contains all the tube feeding supplies.”

Whereas the Melotts pretty much confine their travels to California because Tim still works full time, Betty and her husband Bob, are veritable globe-trotters. They both retired in 1987, she as a rehab nurse.

In May 2007, the Surtees set out for Maine by way of San Antonio, Tucson, Seattle (to put the cats in a kennel) and an Alaskan cruise, she says. After the cruise they picked up the cats and enjoyed the San Juan Islands for a few days, then visited Yellowstone National Park. From there they traveled to a family reunion at Niagara Falls and then toured the Adirondacks before finally visiting the grandchildren at their home in Maine. They arrived home in Cummings, Ga., four months later.

The Surtees prefer to stay in RV parks. “The trick is to get there in early afternoon so there is space available,” Betty notes. “We prefer to use our own facilities, even our own laundry machine — much easier and private. But we always check ‘Trailer Life’ for ratings of the facilities, for cleanliness, as it usually is a clue as to the neatness of the park itself.”

Their trips often include their three granddaughters and Boomer the cat (his buddy Henry the cat died last year). They also tow a small sport utility vehicle for side trips, and put nearly as many miles on it as they do on the RV.

The Surtees sold their “port” or stationary home three years ago. If they feel the need to give the motor home a break, they rent lodging in their old neighborhood.

A lifelong wish fulfilled

Steve and Sandy Ennis of Tullahoma, Tenn., often take their two granddaughters on motor home sojourns these days, although their trips are seldom lengthy because Steve, 67, still works full time as president of Coca-Cola Bottling Works of Tullahoma. They’ve taken two trips to Florida on the Gulf of Mexico and also visited Dollywood. “Steve was in a wheelchair, so he got to hold all of our junk!” Sandy says.

Steve Ennis’ travel gear includes a beach wheelchair. Photo, facing page: The Ennis’ original cruising rig.

Steve has a tracheostomy and uses a ventilator, feeding tube, assistive speech communication devices at home and work, and computers for e-mail at several locations.

Shortly after his diagnosis in summer 2005 and before he needed assistive technology, Steve and Sandy spent five weeks in their RV doing something he’d always wanted to do: traveling the Lewis and Clark Trail from St. Louis to the Pacific Ocean and back. Along the way they visited Glacier National Park, jet-boated the Snake River, heard the Mormon Tabernacle Choir and drove through a tunnel in the base of a giant redwood.

In those days they pulled a full-sized SUV behind their 43-foot RV, but Sandy says that now they usually tow a trailer carrying Steve’s adapted van.

The only modification they’ve made to the motor home is adding a lift that can hoist Steve up to and through the front door. Until he got his trach in 2008, Steve drove, but now pilots only his wheelchair. “But he makes a GREAT backseat driver!” Sandy chuckles.

They’ve also made some personnel changes. “When we travel now, we get someone to help us drive. Also, we might get a nurse to go with us now,” Sandy says.

She counted among the rewards of traveling by motor home being able to take family and friends along, as well as having their own food on board so they don’t have to stop at restaurants.

Challenges remain the same

“The problems with traveling with an RV and a person with ALS are the problems you have wherever you are,” Sandy Ennis says. “You have to take a lot of stuff to care for him, but we have plenty of room in our RV.”

For the Melotts, restaurants are not such an issue. Tim says, “Some people with ALS don’t want to go out in public, but we think it’s important to do that. Ninety percent of the people you encounter are gracious, helpful. Sometimes we have to suction Jackie in public. It’s a fact of our lives and doing so helps us make family life as normal as possible.”

One downside of RV travel is the cost of modifications, he says, calculating that the price of creating the new doorway on his RV was about $7,500, and the cost of the Superarm lift was close to $6,000.

Tim recommends talking to a tax expert about modifications because they may be tax deductible. Further, he says, the cost of replacing an inaccessible RV with an accessible one could be a tax write-off of up 50 percent.  He speaks from experience, as their current big rig is the second one they’ve owned.

Refocusing priorities

Renting an accessible van runs the Melotts about $500 a week. “Yes, it costs a lot of money,” says Tim, an architect and project manager for a large engineering and construction firm. “But you refocus your priorities in life.” His advice to others who may be considering the motor home mode: “Look to see what you enjoy in life, then figure out a way to do it. We enjoyed camping, and we still do.”

The Melotts lived for years in the Philippines, China, Australia and Europe, but they still prefer camping, RV-style, here.

For Betty Surtees, the rewards of motor home travel include “good people along the way, interesting sights to see, beautiful scenery to enjoy and a definite change of pace.”

What will end their RV travels? “Age, not ALS,” she predicts. “We’re getting to that time when it’s advisable to put up the keys to the RV or at least take shorter trips closer to home.”

Banking for the Future

Voice banking technology helps people with ALS ‘capture’ their true voices

by Alyssa Quintero

A voice is an important part of a person’s identity. Personality and emotions echo with every inflection and pronounciation quirk, in every “hello” and “I love you.” A voice is an audible signature that loved ones know anywhere.

Not everyone with ALS loses their voice, but it’s a common symptom, especially in bulbar-onset ALS. While there’s no easy way to prepare for this prospect, “voice banking” is a viable option for preserving your unique sound and the identity it represents.

Voice banking doesn’t have to be complicated or fancy — but starting early is ideal. Banking can range from recording signature phrases and sayings on a tape recorder, to recording audio files on a computer, to recording your voice on a communication device. People record stories, songs, laughter, family jokes, greetings and words of affection.

Oftentimes, the toughest hurdle to cross is simply getting started.

A labor of love

From the moment Tammy Brown of Thida, Ark., stopped trying to convince herself that ALS wouldn’t take her voice, she worked tirelessly to record her voice in multiple ways.

“My children were the main reason I decided to use ModelTalker,” says Brown, 37, who received an ALS diagnosis in 2004. “I didn’t want this disease to totally take my voice away. It may take my ability to speak but not my voice, my spirit.”

In late 2006, Brown began using the free ModelTalker speech synthesis software program (see “Creating a Custom Voice”), which creates a custom computerized voice that includes characteristics of the speaker’s normal voice. By the time she started, Brown already was experiencing some voice weakness that affected her pronunciation.

To complete the ModelTalker ’s full inventory of 1,650 words and phrases needed to produce a natural-sounding synthetic voice, Brown worked on her laptop for at least three hours each day for about two weeks. It was frustrating when ModelTalker wouldn’t accept some words, recalls Brown, who, in addition to voice weakness, had a Southern drawl that seemed to confound the program. But, she says, “it was worth it because I like to hear my voice the way it was before ALS.”

Tammy Brown uses the ModelTalker voice software with her communication device. Brown selects a preprogrammed button to open the ModelTalker dialogue box, and types and speaks messages with her ‘signature’ synthetic voice.

Brown’s husband, Scott, uploaded her voice inventory to the ModelTalker Web site, and about a week and a half later, she received a link to download her free synthetic voice.

Although it’s still a computerized voice, Brown is pleased with the final product and recommends it to “anyone who has the patience to record all of the phrases.” She says her daughter, Lauren, feels closer to her thanks to the ModelTalker voice, as if they’re having real heart-to-heart conversations.

When Brown received a communication device in February 2008 (an ECO-14 from the Prentke Romich Co.), her husband easily transferred her ModelTalker files from their PC to the device.

Currently, Brown uses both her custom ModelTalker voice and one of the built-in voices on her communication device. Although the built-in voice isn’t at all like her own, she prefers it in some situations because it has word prediction (a feature not offered by ModelTalker) which allows her to communicate faster because the device anticipates what she might want to say.

“When I start typing, I have to leave spaces between sentences because they run together and sound funny,” she says of the ModelTalker voice. “My kids laugh at me. It doesn’t pronounce words as correctly as the ECO, but I guess practice makes perfect.”

Tammy Brown (pictured with her son, Logan, age 10 at the time) recorded more than 100 personal messages directly onto her communication device. Now, she selects different buttons on the screen to activate the prerecorded messages, especially for her children and husband.

Brown also “banked” her natural voice directly onto the communication device. With help from family, Brown spent about a month recording more than 100 phrases onto her ECO so her children could hear her say  “happy birthday,” “I love you,” “do your homework,” “clean your room” and other phrases in her natural (albeit weakened) voice.

“My children like some of the sayings I recorded, and they don’t like some, such as ‘you’re grounded,’” says Brown. “My son, Logan, and I laugh at some of the funny stuff like ‘I love you more, I love you to the highest number, and I am proud of you.’ We like watching the dogs jump around and look at me when I call their names.

“Voice banking was a long process, but it was worth every minute,”she says, noting that children will forget the sound of your voice very quickly.”

So much to say: Setting priorities

Speech-language pathologists (SLPs) suggest starting voice banking — in any form — before experiencing any detectable changes in speech. Check with the SLP at your local MDA clinic for assistance and helpful suggestions for getting started, such as lists of commonly used words and topics.

Kathy Thomas, an SLP at the University of North Texas, encourages her clients to work with family members to create a “communication inventory” of personalized messages they will use regularly. Of those messages, decide which ones should be in your own voice.

“Voice banking is a way to maintain personal connectedness,” says Thomas. “We want people to be able to communicate and interact, not just express basic needs.”

Some voice banking tips:

• Review your typical daily routine, including activities and people with whom you interact.
• Make a list of important categories (such as activities and health care needs), and then brainstorm different messages for each category.
• Make a list of specific phrases for certain family members, friends and helpers.
• Include signature phrases and sayings that loved ones identify with you, like greetings, sayings, pet names, jokes, etc.
• When you’re ready to start recording:
• Use a low- to medium-cost handheld microphone or headset mic (USB recommended).
• Choose a quiet environment.
• Pace yourself. Record a few sound bytes, test them, rerecord if necessary.
• Record at the time of day when your voice is strongest, and take regular breaks to keep your voice strong.
• Set realistic goals, and record the most important messages first.

Mary Ann Lowe at Nova Southeastern University in Ft. Lauderdale, Fla., an SLP who works in conjunction with the Kessenich MDA/ALS Center, recommends working with a partner who can help name and save the files following each recording. Because the process can be fatiguing, she suggests resting for about 30 seconds in-between recordings while the other person saves the file.

It’s worth the hassle, says Scott Jeffery, 48, of Trumbull, Conn., who received a diagnosis of ALS in September 2007. “I wanted to have at least some phrases in my own voice,” he explains. (For a description of how Jeffery banked his voice files, see "Creating Audio Files.")

“Like most other things pertaining to ALS, do this early, well before you think you may need it,” Jeffery urges.

“Degradation of one’s voice can sneak up on you. Make this a priority if you would like others to have a better time remembering the ‘real’ you.”

by Margaret Wahl

The American Academy of Neurology (www.aan.com) released its new guidelines on patient care in ALS on Oct. 13, 2009. Several MDA-affiliated physicians were involved in their development.

Aimed at physicians, the guidelines are based on evidence that certain treatments are effective in the care of people with ALS. People with ALS who are not attending an MDA clinic or MDA/ALS center may wish to inform their physicians of the availability of the new guidelines to ensure they’re getting the best care possible.

In developing the guidelines, the AAN used the language “strong evidence” to mean that more than one high-quality study supports the proposed treatment or test. “Good evidence” means at least one high-quality study or two or more lesser-quality studies support the guideline. “Weak evidence” means there are supportive studies that are deficient in their design.

There’s evidence that attending a multidisciplinary ALS clinic (such as an MDA/ALS center) increases survival time and improves quality of life.

Strong evidence

The AAN recommends riluzole, the only drug approved by the U.S. Food and Drug Administration (FDA), to treat ALS. It has a modest effect on slowing the rate at which the disease worsens. Strong evidence shows riluzole can prolong survival.

Good evidence

There is good evidence that the drugs dextromethorphan and quinidine (combined) can lessen the severity and frequency of episodes of uncontrolled laughing or crying that sometimes occur in ALS. (See “Zenvia for PBA” in the Clinical Trials section of MDA’s Web site, www.mda.org, for information about clinical testing of this drug combination.)

There is good evidence that drooling can be controlled using the drug botulinum toxin type B, injected into the glands near the jaw that make saliva.

Maintaining adequate nutrition is difficult when swallowing function deteriorates severely. There is good evidence that a percutaneous endoscopic gastrostomy (PEG) tube or a radiologically inserted gastrostomy (RIG) tube —  commonly called a “feeding tube” —  stabilizes body weight and prolongs survival.

It’s important to undergo tests to detect breathing problems even before they become apparent. If a breathing problem is detected, good evidence shows that a noninvasive ventilation (NIV) device is likely to lengthen survival and slow the rate at which the ability to breathe deteriorates.

Good evidence shows that people with ALS should be screened for possible problems with thinking ability.

There is good evidence that visiting a multidisciplinary ALS clinic (one with many types of health professionals, such as an MDA/ALS center) can help people with ALS get the best possible care. Good evidence also shows that people with ALS who visit a multidisciplinary ALS clinic live longer than those who don’t.

Weak evidence

There is weak evidence that suggests that quality of life improves for people with ALS if they attend a multidisciplinary ALS clinic, and if they use a noninvasive ventilation device.

There also is weak evidence that small amounts of radiation therapy may help with drooling.

MDA’s role

Neurologist Valerie Cwik, MDA’s medical director and executive vice president for research, was part of the AAN Practice Parameter Task Force that developed the physician guidelines. Several authors of the physician guidelines are directors of MDA/ALS centers throughout the United States and/or have received MDA research support.