Are SOD1 Mice Good Models of Human ALS?

by Margaret Wahl

The announcement this spring that yet another promising drug had failed to help people with ALS in a clinical trial has led some in the field to re-examine some assumptions.

Minocycline, an antibiotic with anti-inflammatory and anti-cell death properties, had shown positive effects in ALS-affected mice, but results in humans weren’t the same (see Research Roundup, June).

It joins a list of medications — creatine, celecoxib (Celebrex) and gabapentin (Neurontin) are examples — for which the same story can be told.

The mice used in all research on these medications had a form of ALS caused by a mutation in the gene for the SOD1 protein. The SOD1 mouse develops an ALS-like disease that researchers hope overlaps enough with human ALS that mouse responses to treatment might predict human responses.

SOD1 gene mutations, however, cause a familial (inherited) form of human ALS that’s present in only 1 percent to 3 percent of ALS cases. For some 90 percent of patients, the disease isn’t familial. Its onset is unpredictable (sporadic) and the cause is unknown. (The remaining 7 percent or so have non-SOD1 familial forms of ALS.)

A Different Mechanism?

It may be that SOD1-caused familial ALS and sporadic ALS don’t have as much in common as had been hoped.

The absence of deposits of the TDP-43 protein in tissue samples from humans with SOD1-caused ALS “implies that motor neuron [nerve cell] degeneration in these cases may result from a different mechanism, and that cases with SOD1 mutations may not be the familial counterpart of sporadic [nonfamilial] ALS,” warn the authors of a recent report (see “ALS Research Roundup” ).

It then becomes important, if distressing, to ask: How relevant are research results in SOD1 mouse models to the vast majority of ALS patients?

Jeffrey Rothstein

Story Not Fully Told

Jeffrey Rothstein, who directs the MDA/ALS Center at Johns Hopkins University in Baltimore, says he isn’t ready to give up on SOD1 rodents yet.

“I don’t buy that we’re barking up the wrong tree with the SOD1 mouse,” he says, speculating that TDP-43 deposits may be a feature of the end stage of slowly progressive ALS and that many of the SOD1 patients in the TDP-43 study had a mutation that causes a very rapidly progressive disease. Had they lived longer, they might have acquired the deposits, he says.

However, he adds, “We have to come up with new mouse models and additional means of evaluating drug candidates beyond just the mice. And that’s now being done.”

Teepu Siddique

Teepu Siddique, who sees patients at the MDA/ALS Center at Northwestern Memorial Hospital in Chicago, isn’t ready to give up on SOD1 mice either.

“Right now, TDP-43 is just a marker,” says Siddique, who was an author on the TDP-43 study. “We don’t know what it does. Maybe we are looking at two different kinds of disease, but the story is not yet fully told.”

Lost in Translation?

In his article “Lost in Translation,” published in the April issue of Neurobiology of Disease, Michael Benatar raises questions about the methodology of SOD1 mouse studies.

Benatar, who co-directs the MDA clinic at Emory University in Atlanta, notes that the SOD1 mouse may or may not be a good model of human sporadic ALS, but he says there could be other reasons for its failure to predict treatment responses in patients.

An important consideration, Benatar says, is that most mouse trials treat the animals before ALS symptoms appear, while people are always treated after disease onset.

All About SOD1?

Relatively few researchers propose that abnormal SOD1 protein causes most or all ALS cases. Most think abnormal SOD1 protein molecules are only involved in SOD1-related familial ALS. They look to SOD1 rodent models for insight into the sporadic ALS disease process “downstream of its unknown cause.”

However, there’s one scientist whose interpretation of ALS causation suggests a major role for SOD1 in sporadic, as well as familial, ALS.

Neurodegenerative disease specialist Neil Cashman believes ALS may have a lot in common with prion diseases, which are degenerative disorders resulting from misfolded, toxic proteins. Cashman directs the ALS Centre at the University of British Columbia and is chief scientific officer at Amorfix Life Sciences, a Toronto biotechnology firm.

A prion is a substance that’s able to induce abnormal folding of normal cellular proteins. So far, all the known prion diseases, which include bovine spongiform encephalopathy (mad cow disease) and others, are caused by a misfolded PrP protein that acts as a folding template and causes otherwise normal PrP protein molecules to assume an abnormal, toxic shape.

Cashman wants to find out whether ALS is a disease of misfolded SOD1 protein molecules, arising in some cases from a mutated SOD1 gene and in others from a random misfolding of a normal SOD1 protein molecule.

His hypothesis, for which he has some evidence and is gathering more, is appealing, because if it’s true, it implies that SOD1 rodent models are a good replication of human disease after all.

“I think the SOD1 models are great models for protein aggregation [clumping],” Cashman says, “but they don’t capture a critical feature of [human] ALS, which is propagation of the disease.” To do that, he says, they’ll  need some tweaking.

Disease Propagation

The SOD1 animals, he notes, are “transgenic,” meaning they’re born with mutated human SOD1 genes in every cell (as are people with mutated SOD1 genes). There’s no spread of the disease in SOD1 transgenic mice, he notes. “It presents simultaneously in the most affected regions, the hindlimbs,” he says.

“In sporadic ALS, there’s this creeping paralysis, which may reflect a propagation of the disease throughout the nervous system. I think it’s crucial to our understanding of ALS.”

In Cashman’s ALS hypothesis, the regional spread of weakness is caused by the gradual spread of misfolded SOD1 protein molecules.

It could be argued that this hypothesis doesn’t hold up, because humans with mutated SOD1 genes, present from birth, also show gradual spread of paralysis.

But Cashman believes that human SOD1 mutations aren’t by themselves enough to cause ALS. This is supported by the long delay between being born with an SOD1 mutation and disease onset, usually some 50 years later, as well as the lack of 100 percent correlation between having an SOD1 mutation and developing ALS.

“You can have a mutant protein that functions normally for 50 or 60 years, and you can bear mutant SOD1 for an entire lifetime without developing disease,” Cashman says. In his model of ALS, “there’s an event that must occur. The mutation itself is not enough to produce the disease.”

The event, he says, could be a viral infection or another type of stress to a cell. But “once the template is established, the process propagates and runs its course.”

“I don’t think we’ve wasted our time with the SOD1 mouse models,” says Jonathan Glass, director of the MDA/ALS Center at Emory University in Atlanta. “I think we’ve learned an enormous amount. But we can’t just keep banging on the same nail with the same hammer.

“We need to understand the mechanisms that underlie the disease and develop hypotheses based on these mechanisms and not necessarily on mouse tests. Using mice as gatekeepers for determining which drugs go on to clinical trials is probably not going to be the case anymore.”

Glass says he doesn’t think we should “jump to human trials quickly,” but he’s also “not sure if taking the extra step of going to the mouse is the best way to do it.” It might be better to identify mechanisms in humans and then find a way to test drugs based on those data, perhaps through a test tube screening process.

“The human is the best model we’ve got,” he says.

Siddique says he thinks SOD1 mice will continue to be used until we have better models. SOD1 models, he says, are “low-hanging fruit.”

The higher fruit may be out of reach for now, but eventually we’ll get there, he says. He noted that a key aspect of Parkinson’s disease pathology was found as a result of a gene mutation identified in only three families.

What Will You Do If the Power Goes Out?

by Bill Norman

Summer and fall typically bring storms that cause power outages — not a comforting thought for people who rely on electrically powered equipment to breathe.

Fortunately, preparation can reduce the impact of power outages, even when hurricane-magnitude disasters strike.

Existing Backup

Those who use portable ventilators already have a power option if household power goes out — the unit’s batteries. 

Many portable and nonportable vents also include a small backup battery that provides about an hour of power. Some vents have two primary batteries, so if one declines significantly, the other automatically kicks in.

How long will a full battery charge last? That mainly depends on the type of battery and how much power the medical device requires. Portable ventilator batteries are rated at anywhere from three to nine hours, but may run longer or shorter depending on external conditions.

Switching to lithium-ion batteries can add an additional two or three hours of use. These batteries also are lighter than standard lead-acid batteries, and recharge in only two to three hours.

Lightweight lithium-ion battery pack

Although some feel confident just relying on the vent’s batteries, others want another source of backup power, in case of long outages. Following are tips, precautions and equipment options for those who want to take added measures.

How Much More Power is Needed

Many vents draw between 200 and 400 watts of power. But to be safe, the power source should provide more than the specified wattage. If the necessary power isn’t there, the device can’t perform its vital job.

Vent owners need to know the operating specifications for their particular unit when shopping around for backup power.

Use the Car

One alternative is to plug the vent into the power outlet (lighter socket) in a car or van, tapping the energy of the 12-volt direct current (DC) automotive battery. Some vents come complete with a lighter socket adapter and cord. For others, after-market setups may be an option (contact the vent manufacturer).

It’s recommended that the vehicle’s engine be running during use, so its battery is continually recharging. This must be done outdoors to avoid carbon monoxide buildup, meaning the vent user probably will have to sit inside of, or close to, the vehicle.

Those planning to use this backup power approach should be sure to keep their vehicle’s fuel tank at least half full.

Solo Batteries

Deep-cycle 12-volt marine batteries provide several hours of electrical power. DC cables (the same type as used for lighter socket connections) and clamps (available at hardware stores) are needed to connect to the battery terminals. The vent already may have its own input connection to attach the cables, or one may be recommended by the vent manufacturer.

However, when marine batteries quit, it happens all at once with little warning. For that reason, those using this type of power arrangement should have more than one battery on hand. Also needed is a charger to ensure the batteries stay at full power during storage.

A standard automotive battery can work in a pinch, even as a stand-alone unit. But as its charge declines, electrical output also gradually declines, meaning a vent could begin hesitating and laboring because it’s not receiving all the power it needs.

Generators

Gasoline- and propane-fueled generators provide a steady source of alternating current (AC) electricity. There are basically three options:

1. A small, lightweight, portable “camping” generator (1,000 to 2,000 watts) will power a ventilator or related device.  Typical price range: $200 to $800. 
   
   Example: Yamaha EF1000is. This 1,000-watt unit produces either 120-volt AC or 12-volt DC power. Weight: 28 pounds. Cost: about $750. Runs up to 12 hours on less than a gallon of gas. Features an inverter to even out fluctuations in energy flow (see “Pure Power”).
   
   
2. A mid-range portable generator (3,000 to 10,000 watts) can power not only a vent, but household lighting and appliances like refrigerators. Cost: $200 to $2,500. Manufacturer-reconditioned models cost less.
   
   Example:  A reconditioned Generac 4000XL produces a maximum 4,000 watts and 120 and 240 volts of AC power or 12 volts DC. Runs up to seven hours on one 4-gallon tank of fuel. Price on E-bay: $200.
   
   

Portable battery packs supply hours of back-up energy.

3. A large automatic-start generator (7,000 to 40,000 watts) fires up immediately if house power goes out. Low-end units (starting at about $2,000) may power several electrical circuits in the house, while high-end units ($10,000 to $12,000) can power the entire home. If connected to a natural gas line or large propane tank, these big units have an essentially unlimited fuel source.
   
   Downsides to generators are that less expensive ones are noisy and must be started by yanking on a cord. More costly units have push-button starters.

Most importantly, many generators don’t provide the consistent “medically rated” current needed for sensitive electronics like vents (see “Pure Power”).

All generators must be operated outdoors due to poisonous fumes. Generators should be tested every seven to 10 days to ensure they’re tuned and ready. Adding several drops of fuel stabilizer (available at auto parts or hardware stores) keeps gasoline fresh.

Uninterruptible Power Supplies

Uninterruptible power supply (UPS) systems combine a surge protector and a backup battery.

Ordinarily, a ventilator plugs directly into a wall outlet. The UPS becomes a “middle man” in the arrangement. The UPS plugs into the wall outlet; the vent plugs into the UPS. When household current is working, it sends power through the UPS to the vent. A charger in the UPS keeps its batteries up. When electrical power fails, the UPS batteries take over the job of powering the ventilator for up to several hours, depending on the size of the UPS system.

Medically rated UPS units contain powerful surge protectors that can prevent ventilators from being “fried” if lightning strikes the home.

It’s possible to combine a UPS with a gas generator. If the UPS batteries fade during a prolonged outage, the unit can be plugged into the generator, which not only provides fresh power but also recharges the UPS batteries.

Typical cost of a medically rated 1,000-watt UPS is $3,200.

Head for the Hospital

Most hospitals have backup electricity-generating systems that spring into action when the main power supply is interrupted.

Vent users with limited resources for backup power should check with their doctors and/or area hospitals to see if using the facility’s emergency power is an option in a prolonged outage.

Think Ahead

The secret to coping with a serious electrical power outage is to be prepared, not only with an in-depth plan for backup power, but with “rehearsals” of all the steps needed to keep critical medical equipment functioning smoothly in an emergency.

'Pure' Power Stand-alone power inverter Batteries produce direct current (DC) electricity that’s ideal for operating medical equipment such as ventilators. But most generators produce alternating current (AC), and not all AC is created equal. Household AC usually is what’s known as pure, or near-pure, sine power, meaning the current has very few fluctuations and is considered “clean.” But AC current produced by some generators fluctuates and is sometimes described as “raw.” Raw-power units aren’t medically rated. A split-second hesitation in the function of a refrigerator probably isn’t noticeable, but sophisticated electronics like ventilators are another matter. To assure seamless operation, a generator should be equipped with an inverter device to produce near-pure sine energy. Of course, these medically rated generators cost more.

Lisa Shelley: Her gift bags are a token of love

by Bill Norman

Lisa Shelley decided more than a year ago that ALS would take a back seat in her life. In the foremost position she opted for humanity — or more specifically, helping others.

Through her program Friends Like Mine, Shelley prepares gift bags for the MDA/ALS Center in Charlotte, N.C., where staff give them to people who have just learned they have ALS.

The bags contain $50 gift certificates donated by local Harris Teeter grocery stores.  With money she raises with help from her church and the community, Shelley also purchases Barnes & Noble, Target and Starbucks certificates. Rounding out the package are a journal, bookmark and body lotion.

Shelley hopes her gift bags tell people with a new ALS diagnosis "they are not alone."

“The bags are a small token of love. They are not meant to be a reminder of the disease, but a means to take patients’ attention elsewhere for a few moments,” Shelley says. “I want them to know they are not alone. No battle is won alone, and I plan to fight this one for a long time.”

Shelley, 45, co-owns Nails Plus, a nails and hair salon in High Point, N.C.  She learned she had ALS in February 2006.

David Stephenson, MDA regional field representative in Charlotte, says, “I’m not sure I can ever do justice to telling Shelley’s story. She has lived her life helping others, including serving years as a caregiver. It is remarkable to see her donate her time and energies to such a worthwhile mission while daily trying to manage her own difficulties associated with this terrible disease.”

Shelley currently serves on the planning committee for MDA’s 2008 Road to a Cure Gala in Greensboro which raises funds for ALS research. At this year’s event in March, she was honored for her efforts in raising awareness of ALS.

“Her desire to make this a special year created a buzz throughout the entire community,” Stephenson said. “Largely due to her efforts, we are expecting 500 people at our next gala, which is pretty spectacular given that this is only its second year.”

In February, Shelley began participating through the Charlotte MDA/ALS Center in a clinical trial of the antibiotic ceftriaxone as a potential ALS treatment. She says it will be a lengthy process, but she has high expectations of its results.

“MDA has been so good to me. I love working on the road to a cure, and I believe it will happen. In working to raise money for research, I also have gained a good idea of where it’s headed. It will benefit me, yes, but it will also help thousands of others,” she said.

FIRST PERSON SINGULAR
A Magic Carpet Ride

by Erin Brady Worsham

March 21, 2007.  I’m sitting in an adaptive bi-ski at the top of Crawford’s Blaze run, at the Bretton Woods Mountain Resort in New Hampshire. Across the valley I have a beautiful view of the Presidential Range of the White Mountains. What’s a girl from Nashville, Tenn., who’s almost completely paralyzed from ALS, breathes with a ventilator and has never skied before in her life, doing here? It’s a long story ...

Think Ahead

I love watching finely tuned athletes at work, especially since I have little or no muscle myself. But the Olympic Games commentators on TV spend too much time talking about the athletes’ personal lives. I love the sport, not the melodrama. 

A volunteer "tetherer" glides the author down Crawford's Blaze run. All photos courtesy of Bretton Woods Adaptive Ski program.

Who was this Bode Miller everyone was crucifying on and off the slopes? Their comments made me take a closer look at alpine ski racing.  What I discovered was an excitingly unpredictable sport, where .01 of a second could win the day. I was hooked.

Bretton Woods Adaptive Program

I was ashamed at how little I knew about the U.S. alpine ski team. I set to searching the Internet to educate myself on the sport and its athletes, and discovered that Bode Miller supports the Bretton Woods Adaptive Program. This incredible program allows people with a wide range of disabilities to ski using specially trained instructors and adaptive equipment. 

by Erin Brady Worsham

Though I felt myself beyond the abilities of this program because of my spaghetti body and ventilator, I still was inspired to create a computer art piece called “Go Fast”  (see cover). In it, Bode Miller guides me down an impossibly steep slope on a sort of sit-up sled. This picture expressed the freedom I felt when I watched alpine ski racing. I e-mailed my picture to the Bretton Woods adaptive ski program on April 28, 2006.

Cris Criswell, acting program director, e-mailed me the next day. He included a picture of himself on his mono-ski. Cris, a retired business executive, took up mono-skiing 10 years ago as therapy for his post-polio syndrome. 

Also in the picture was Tom Wade, a history teacher from Milford, Conn., sitting on an adaptive bi-ski. Wade, a quadriplegic, is tethered down the mountain by another skier from behind. It was my first inkling that someone like me could ski. Cris cleverly planted the seed, and then sat back and let it grow. 

On June 13, Cris broached the subject of our coming to Bretton Woods. “What do you think?” he asked me by e-mail. 

“I think I think about it every day,” I said. “I think God is telling me to get my butt up there.” The adaptive program had never dealt with someone quite like me! I think I was a challenge! 

But New Hampshire is a long way from Tennessee.  It would take two long days of driving to get there.  I couldn’t even consider a trip of that length without another adult to help my husband, Curry, care for me and our son, Daniel, 11.  Our good friend, Iva Webster McGavock, came to our rescue.  On Feb. 4 this year, I gave Cris the green light.  We were going to New Hampshire.

The Ventilator

As the day of our departure drew near, my respiratory people at Apria Healthcare started to panic. Their Littleton, N.H., office had reported a temperature of 9 degrees Fahrenheit. According to the maker of the ventilator, Pulmonetic Systems, the optimum temperature range was 41 to 104 degrees.

If my circuits seized up, I’d have to go to the hospital until they could locate another special-order ventilator like mine. But I always travel with a backup ventilator, and the weather forecast was for the low 30s and 40s.  We went ahead with our plans.

Bretton Woods, N.H.

We pulled into the Bretton Arms Country Inn, on the grounds of the famous Mount Washington Hotel, at 4:47 a.m. on March 20. I had just enough energy to take in the white clapboard charm of the old inn, which was built in 1896, before falling asleep in our spacious wheelchair-accessible room.  The morning sun revealed the startling beauty of the White Mountains all around.

Safety concerns take top priority as the author is fitted and fastened into a bi-ski.

The next day we met Cris and Sandy Olney, the incoming program director, in the base lodge. Cris had suggested we have a dry run to work out any kinks.

We were shown two models of bi-ski. Neither had any head support, so Curry suggested bolting the headrest from my wheelchair to the back of the bi-ski. A template was taken, a plate was made and attached, and we were ready for the transfer. Sandy, whom I dubbed Earth Mother because of her kind eyes and long golden braid, held my head while they moved my headrest.

Curry transferred me into the bi-ski and I was tightly belted into the seat. Every detail was addressed.  These people are about safety — they don’t want any surprises!

The Launch

Run Day, March 21, dawned clear and sunny with brilliant bluebird skies. It was supposed to get up to 32 degrees.  I knew that between the sun and a warm blanket over the ventilator, we could reach that 41-degree benchmark.

George Hollingsworth and Dave Blenkhorn, the master tetherers on loan from the White Mountain Adaptive Ski School at Loon Mountain, N.H., would be taking us down the mountain. Curry would be riding on another bi-ski, to be near me if there was a problem.

We decided to leave one external battery for the ventilator with the chair lift operator at the bottom and one at the top. I would be going down the mountain on the ventilator’s internal battery, which was supposed to have 60 to 80 minutes of power.

The ventilator was taped down over my shins, the tubing was taped to the ventilator, and a blanket was taped over it all. My hands were taped into warm ski hats and then onto my lap. We were ready.

Dave skied me over to the chair lift and, without stopping the lift, he and George hauled the bi-ski onto the seat between them. I felt no fear on the chair lift, only wonder at finding myself soaring over the heads of skiers and snowboarders flying down the hill.  At the top, the view of the White Mountains was stunning!  We stopped to take pictures.  Curry got in his bi-ski and we were off. 

Crawford's Blaze

I was amazed by how fast and smoothly the bi-ski rode under Dave’s direction.  We headed down Crawford’s Blaze, a tree-lined, winding run with breathtaking views of the mountains.  My paralyzed body moved forward naturally into the turns.  It felt exhilarating and strangely familiar. 

As the grade got steeper, Dave crisscrossed the slope with shallower sweeps. At the end of each sweep was a jarring bump that threatened to dislodge my head.

Halfway down the run my ventilator alarm started sounding.  The “battery low” warning was flashing! I couldn’t have been using the internal battery for more than 25 or 30 minutes. I’d never tested the ventilator battery past that warning. 

Dave took a more direct line down the hill, which resulted in a few more bumps. Out popped my head! Three people converged on me, and within 30 seconds they had fashioned a chinstrap out of duct tape that attached to my headband.  Thank God for duct tape!

Dave took a very direct line at the end that gave me an incredible rush.  The only problem with our plan to have batteries at the top and bottom of the mountain was that the cable to attach it was left at the top! Dave and Sandy got me inside and Curry ran to the car for the power cord to plug the ventilator into the wall.  As he plugged it in, I saw a warning I had never seen before: “Battery empty”!

Epilogue

We were later told by the respiratory people at Apria that the ventilator had to work harder at the top and bottom of those ranges, and therefore ran through its internal battery more quickly.  Well, why didn’t they say so before!  We were prepared for any eventuality, since I had my Ambu bag and suction machine with me. 

"Go Fast" comes to life for the author. For information about the Bretton Woods Adaptive Ski Program, call (603) 278-3398 or e-mail: adaptiveprogram@brettonwoods.com

Besides Dave, George, Cris and Sandy, many trained volunteers made my skiing dream come true. This program’s lifeblood are its volunteers and I can never thank them enough.

So, why did this Tennessee girl feel the need to make a pilgrimage to the White Mountains?  Cris, who is also a minister, put it best in an invocation he gave at the annual Hartford Ski Spectacular in Breckinridge, Colo. 

“It is our magic carpet ride.  We all glide over frozen, sparkling crystals for the same reason, to be transported into another world.  A place where the crippled dance, the lame walk and the blind see, where we may all, each and everyone, no one left behind, all together, mount up with wings like eagles and join the dance which has no end.” 

Amen to that!

Erin Brady Worsham, 48, received an ALS diagnosis in 1994 and a tracheostomy in 1997. She’s an award-winning computer artist.

Research Links Hospice Care With Prolonged Life

by Amy Labbe

Contrary to popular belief, hospice care seems to prolong the lives of some terminally ill patients by days or even months, according to a recent study funded by the National Hospice and Palliative Care Organization (NHPCO).

The study, published in the March 2007 issue of the Journal of Pain and Symptom Management, showed an average 29-day increase in length of survival for people who received hospice care, compared to those who didn’t.

Researchers studied 4,500 terminally ill patients affected with congestive heart failure or cancer of the breast, colon, lung, pancreas or prostate. Results were broken down by disease and indicated longer survival rates for those receiving hospice care in four of the six categories.

The two areas in which increased survival rate wasn’t seen were breast cancer and prostate cancer; researchers didn’t speculate however about why hospice care might benefit those with one disease more than another.

What is Hospice?

Hospice care is a service available to people in the end stages of a terminal disease.

Hospice staff and volunteers coordinate with the patient, physicians and family members to provide day-to-day care and comfort. Services include administering medications, including those to ease suffering; performing personal hygiene tasks and minor medical procedures; and offering compassionate companionship and support. Many hospice services provide support to the patient’s family as well.

In general, hospice patients receive only comfort care and symptom management, not life-prolonging devices or therapies. However, pre-existing feeding tubes are OK and some hospice programs also accept patients who already are vented.

Hospice care often is provided in the home, but can be conducted in hospice centers, hospitals, nursing homes or long-term care facilities.

Cost is covered under Medicare, Medicaid, and most private insurance plans.

Longer Lives

Researchers pointed to several factors that may explain their finding that hospice actually prolongs life:

• The risk of overtreatment — such as the administration of aggressive therapies — is decreased for those in an already weakened condition.
  
  
• More personalized attention may result in improved monitoring and treatment.
  
  
• Hospice care offers a comprehensive approach, focusing on the patient’s emotional and spiritual needs in addition to physical health.
  
  
• Family caregivers are offered support and training. Their reduced stress or workload may help patients feel like less of a burden, and so increase their desire to live.   

Whatever the reason, the numbers are encouraging for those considering the service for their loved ones.

“There’s an inaccurate perception among the American public that hospice means you’ve given up,” NHPCO President and CEO J. Donald Schumacher said in a press statement. “Those of us who have worked in the field have seen firsthand how hospice can improve the quality of, and indeed prolong the lives of, people receiving care.”

by Alyssa Quintero

While there’s no easy way to prepare for losing your voice, voice banking enables people with ALS to capture their voices via recordings that can be used on Windows-based computers and alternative augmentative communication (AAC) devices.

To start, you can record your voice on a Windows-based computer using the sound recorder accessory and saving your recordings in waveform (.wav) files. Many people record signature phrases like “I love you,” or stories for their children and grandchildren, songs and laughter.

Advances in AAC technology allow some programs to use your prerecorded voice on your speech-generating device. You can import the audio files from your PC, or record your voice directly onto some AAC devices.

Speech-language pathologists (SLPs) suggest thinking about voice banking — in any form — before experiencing any detectable changes in speech.

Laurie Sterling, an SLP at the MDA/ALS Center at the Methodist Neurological Institute in Houston, explained, “It’s never too early to start [voice banking] following a diagnosis because it’s difficult to determine when there will be speech changes and to what degree.”

ModelTalker Replicates Your Voice

The ModelTalker Speech Synthesis System’s voice-banking technology uses representative segments of a person’s recorded speech [from a syllable to a sentence in length] to create a unique synthetic voice, which can be used on a speech communication device.

People are attracted to this technology because it captures recognizable characteristics of the person’s original voice, explained H. Timothy Bunnell, the project’s principal investigator and head of the speech research lab at the Alfred I. duPont Hospital for Children in Wilmington, Del.

“We take natural speech that’s been recorded, chop it into small pieces that we can mix and match, and put them together in a variety of ways to produce utterances that were never recorded but that sound like they’re the same quality and from the speaker who did the original recordings,” Bunnell said.

Although the software’s still under development, Bunnell said it’s been used by a number of people with ALS. It can be downloaded at no cost. The software requires a Windows-based PC with audio capabilities and a head-mounted microphone.

ModelTalker requires recording about 1,600 utterances, which equals about 45 minutes of speech.

“We’re recording a fraction of the amount of speech that’s recorded for the commercial [AAC] systems, so it doesn’t sound as natural as they do,” Bunnell explained. “But it’s substantially better than the DECtalk voices that people used to listen to.”

Developed in the early 1980s by the Digital Equipment Corp., DECtalk turned text into human-like speech, albeit with a robotic quality.

Is That Really You?

The ModelTalker Speech Synthesis System’s voice-banking technology uses representative segments of a person’s recorded speech [from a syllable to a sentence in length] to create a unique synthetic voice, which can be used on a speech communication device.

Don Taylor of Collierville, Tenn., who received a diagnosis of ALS in January 2005, hasn’t completely lost his voice, but he believes it’s only a matter of time.

When he learned about the ModelTalker project from his speech therapist nearly a year ago, Taylor immersed himself in a monthlong voice capture project using ModelTalker.

“A person’s voice is special and unique to his family and friends, and ALS robs you of this important trait,” said Taylor, 50, via e-mail. “I’m really pleased with my synthesized voice.”

Only family members can understand Taylor’s speech at this point, so he expects to be using his new voice full time.

Don Taylor is happy with his ModelTalker voice.

Taylor recorded 1,649 utterances using his laptop computer and a USB microphone. He’s worked with computers for more than 20 years, so he had an easy time with the software, but users also can e-mail questions to the lab (via the ModelTalker site).

He recommends working on the project when your voice is strong, typically first thing in the morning. For three hours each day, he recorded 50 to 100 utterances. Because he was experiencing speech problems when he began recording, he had to repeat each utterance about four times to achieve good quality recording.

InvTool, the system’s computer-assisted voice-recording software, uses performance meters to provide feedback on pitch, loudness and pronunciation, ensuring that the recordings remain as similar as possible. Uniformity is essential to making a high-quality synthetic voice.

After uploading to the lab’s database, Taylor’s voice was analyzed and converted into his synthetic voice. ModelTalker provides users with a link to download the voice files.

The synthetic voice can be used with any speech communication system that’s SAPI 5.0 compatible. SAPI, or Speech Application Programming Interface, was created by Microsoft to use speech-recognition and speech-synthesis systems within the Windows operating system.

Otherwise, ModelTalker can be used as a stand-alone text-to-speech application that lets you type text into a window on an AAC device or computer, then hear it spoken using your synthetic voice.

Currently, Taylor’s using his ModelTalker voice on a laptop computer, along with EZ Keys and E-triloquist speech communication software. Both work with the Windows operating system, and E-triloquist can be downloaded at no cost to people with ALS.

“When I type words on my computer, people hear my voice instead of a fake computerlike voice, and that’s why ModelTalker is so valuable,” Taylor emphasized.

His wife, Hing, and three children are pleased he took the time to record his voice “because when it’s totally gone, the ModelTalker project will allow them to hear my real voice even if it’s coming out of a computer speaker.”

Before Taylor received his synthetic voice, he’d recorded over 100 phrases using the Windows Sound Recorder. His favorite recording is the “Happy Birthday” song.

He recommends that people with ALS record their laughter, too. You can’t record laughter using ModelTalker, but he said that “it’s super simple on any computer, and your family will appreciate it.”

It's Not Perfect, Makes No Guarantees

Because ModelTalker is experimental, beta-test software, there are no guarantees. Bunnell cautions users to have realistic expectations about their new synthetic voice, because it won’t sound exactly like their real voice.

To get a taste of the synthetic ModelTalker voices, visit the Web site to hear sample female and male voices — the original voice and its synthetic derivative. Most voices come from people with ALS.

Taylor said, “I have to admit that my synthesized voice is not perfect, but I should have started recording my voice with ModelTalker six months earlier when my voice was strong.”