Clinical Bulletin from The ALS Association National Office

Last week, Canadian media released a story about a woman with ALS who has been treated for the last 18 months with an AIDS cocktail. She and her ALS physician, Dr. John Turnbull of McMaster University in Ontario, Canada, report that her disease has slowed down and some symptoms have improved or gone away. This is an encouraging report and ALSA is pleased to learn that Dr. Turnbull has begun a small clinical trial with this cocktail of AIDS drugs. Results of this trial will be available later this year.

ALSA's perspective and comments:

· There is no peer-reviewed evidence at this time that indicates that the "AIDS cocktail" also known as HAART (highly active antiretroviral therapy) is beneficial to people with ALS. There can be significant side effects with this therapy. Until more is learned, ALSA is cautious about taking the report of a single case study as an indicator of what the treatment might mean to a population of people with ALS.

· Two reports appeared in the medical literature in 2001 describing studies in which HIV positive patients with accompanying ALS-like syndromes showed stabilization or partial recovery of the ALS syndrome after starting antiretroviral therapy. (see http://www.alsa.org/news/news092801.cfm)

· Encouraged by these initial published reports, ALSA is sponsoring a small pilot study to test whether patients with ALS who are negative for HIV would show similar reversal of symptoms when treated with Idinavir, a protease inhibitor (different from that in the HIV cocktail, but in the same class). Idinavir was selected because it can cross the blood brain barrier. This study will be completed in May 2003 at which time results will be made available. (see http://alsa.org/research/scicur111.cfm)

· Studies to investigate whether retroviruses are involved in ALS are in progress. The protease inhibitor Indinavir and the related compound in the AIDS cocktail may be effective in preventing caspase-dependent apoptosis (a cell death pathway involved in motor neuron degeneration). More evidence from animal studies are necessary to support this hypothesis.

· ALSA is currently unaware of any other trials using the AIDS cocktail. ALSA will keep the ALS community informed should we be alerted to any other ongoing efforts.

ALSA is always watching for anything that will make a difference in this horrendous illness. ALS medical literature includes reports of some cases in which the individual's disease fluctuates. The ALS community needs to have data from carefully controlled and well-designed laboratory and human studies to be confident that this or any treatment is truly safe and effective for ALS. The published results of this one case study, the pending results of the Indinavir study, and the data from the small clinical trial Dr. Turnbull has begun will provide important information to substantiate whether this therapeutic approach holds the promise for others with ALS.

PEOPLE WITH ALS SHOULD CONSULT WITH THEIR NEUROLOGIST CONCERNING THIS INFORMATION.

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Elizabeth had a terrible secret.

She was getting well.

The knowledge that her body was rallying gnawed at her. Made her weep. Sometimes the guilt would rise to her throat and she'd choke it back.

While others around her were dying, Elizabeth was getting better. And she wasn't allowed to tell anyone why.

For 18 long months, others would mistake Elizabeth's emotions for something else -- the fear of death, the frustration of losing control of her body, the pain brought on by an incurable illness. But they never guessed that what was wrenching her gut wasn't her impending death -- it was the prospect of staying alive longer than she, or any doctor, ever expected.

Elizabeth Grandbois is the first person in the world to take the AIDS cocktail as a treatment for ALS (amyotrophic lateral sclerosis).

And it seems to be working.

Doctors around the globe are waiting with bated breath to learn if this Burlington woman has experienced the first viable treatment for the cruellest of all neurological diseases. ALS -- also known as Lou Gehrig's disease -- destroys the body while leaving the mind intact. It turns the body into a coffin.

Elizabeth was diagnosed with ALS in November 1997 when she was 45. She and her doctor figured she had just a couple of years before she would lose her ability to walk. That by the new millennium she'd no longer be able to speak and she would need a feeding tube. And that by now, she'd be dead. The best she could hope for was it would all happen quickly.

She never imagined her demise might slow to a crawl. Or some symptoms of her ALS might actually disappear.

"We're watching an experiment unfold before our eyes," says Dr. John Turnbull, Elizabeth's physician and founder of the McMaster University Medical Centre's ALS clinic.

The initial impact of ALS on Elizabeth's life was swift. She could no longer work as an emergency room nurse or ride her horse. Sometimes she would fall and her husband or children would have to help her up. A walker was necessary to help her cross the living room. Swallowing became difficult, the muscles in her face changed and affected her smile.

Her voice wavered.

Even as her muscles weakened, Elizabeth's spirit remained strong. She made it her mission to educate the public about ALS and raise funds for research. She became active with the ALS Society of Canada and met dozens of patients from across the country.

Like them, Elizabeth watched hopelessly as her condition worsened -- until the spring of 2000.

Turnbull told her about an article he'd read in a medical journal. It told of a 32-year-old woman in New York who was HIV-positive and rapidly began to develop symptoms of ALS.

Her HIV was treated with the AIDS cocktail -- a powerful mix of drugs that have drastically slowed the progress of AIDS -- and suddenly her ALS completely disappeared.

The drugs had slowed the death of the woman's cells. Four years later, the patient's ALS symptoms had not returned.

Could an ALS patient who is not HIV-positive have the same results with the AIDS cocktail?

Turnbull wondered.

"If you want to try this sort of approach, I'd be willing," he told her.

Nobody in the world had ever gone down this path before. There would be bumps. Some small in comparison to the certain death that awaited Elizabeth at the end of her journey through ALS. Some so large that her family may never be able to cope.

First, the possible side-effects: anemia, bleeding, liver damage, blood sugar problems, allergies, diarrhea, nausea ...

Small prices to pay for a miracle, thought Elizabeth.

Then there was the cost: $1,500 a month for the drugs. Again, Elizabeth and her husband, Marc Grandbois, decided it was a small price to pay.

There was the possibility that for all the suffering, all the cost, Elizabeth might get nothing in return. The AIDS cocktail may not help her.

In April 2000, Elizabeth became a guinea pig. Twenty-two pills a day. Half of those are the so-called cocktail, more formally known as HAART -- highly active anti-retroviral therapy. Some of the others are also prescription drugs. And six of the daily pills are vitamins.

Within a few days of taking her first dose, Elizabeth felt stronger.

"I thought maybe it was just in my head," she says. "Look, I can tap my toes now. I can lift my foot."

Small improvements indeed. But, over the next few months, there were more.

"My voice went back to almost normal. My swallowing stabilized. I felt like my smile was back."

Marc began videotaping his wife's walk. When she started taking the cocktail, she could barely climb the stairs to the second storey of their home. She could walk up without stopping after a few weeks.

Elizabeth was feeling better than she had since being diagnosed. There were no side-effects at all from the powerful drugs. She still worried her wellness was only wishful thinking.

"Hardly anybody ever feels better," says Turnbull.

"No matter what their outlook, this disease just keeps on going."

Except for Elizabeth.

Her electromyogram (EMG) -- which is always abnormal in ALS patients -- began to improve.

"Significantly," according to Turnbull. The EMG showed an improvement of the electrical activity in Elizabeth's muscles, and it was the first objective proof she was getting better. Other tests showed no deterioration in her muscle cells and some increased strength, something that never occurs with ALS patients.

The new challenge was to find out why. Was Elizabeth an anomaly, or were the drugs working?

While 90 per cent of ALS patients die within two to three years of being diagnosed, another 10 per cent live as long as 10 years.

Perhaps Elizabeth was one of the lucky ones. And at least one patient -- renowned physicist Stephen Hawking -- has been living with ALS for 40 years.

Meanwhile, other ALS patients wondered about Elizabeth's miraculous improvements. As their own bodies failed and they sped toward their own deaths, they marvelled at their friend's improvements.

For 18 months, Elizabeth couldn't share her secret. When Turnbull introduced the idea of the AIDS cocktail, he asked her not to tell anyone except close family. The whole issue of the drug therapy -- and the request for secrecy -- was a hugely difficult ethical dilemma for Turnbull.

"ALS is a terrible disease," he says. "But it would be unethical to put everyone on these drugs without any proof (that they work)."

Turnbull didn't want to give ALS patients false hope. He also didn't want to give them drugs that could make them sicker than they already were.

So Elizabeth watched her friends deteriorate. She even watched some die. And she said nothing.

"I felt so guilty," she says.

She felt as though she was being dishonest to her friends and to the public at large. By then, Elizabeth was gaining celebrity status through media interviews about ALS and as the organizer of Elizabeth's Concert of Hope, a hugely successful fundraising event launched in Hamilton three years ago.

The annual concert takes the stage Feb. 8 at the duMaurier Centre.

Elizabeth was working hard to raise awareness and money for ALS research but she couldn't tell anybody that she represented what was perhaps the world's greatest breakthrough in ALS treatment.

Eventually, she couldn't be silent any longer. After 18 months of taking the cocktail and celebrating her improvements, Elizabeth told Turnbull that she had to share her story.

He agreed. Now, 12 Hamilton area residents with ALS are part of a formal drug trial conducted by Turnbull and paid for by the GlaxoSmithKline pharmaceutical company. There is room for three more patients.

As for Elizabeth, her ALS has not advanced much at all since she started taking the AIDS cocktail:

"I still make meals, I still do laundry. It's moving along at a snail's pace.

"I believe the way I'm going, I have probably another good three years."

Elizabeth knows the drugs she takes aren't a cure for ALS.

"But now I have a sense of hope."

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Ride for Life Editor's Note:

Here is the contact information for Dr. John Trumbull and the McMaster University ALS Center:

Dr. John Trumbull turnbull@mcmaster.ca

McMaster University Hospital Neurology Department
1200 Main Street West, Room 4U7
Hamilton, ON L8N 3Z5
Tel: 905-521-2100 Ext. 76870
Fax: 905-521-2656

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A gamble on an unproven treatment could help patients with ALS, or Lou Gehrig's disease. An Ontario woman has become the first person in Canada to take AIDS drugs to slow the progress of ALS. Scientists say her case could be a clue in understanding this dreaded disease.

Elizabeth Granbois is one of about 3,000 Canadians with ALS, or amyotrophic lateral sclerosis. It's a debilitating and degenerative disease that weakens muscles, causes paralysis and eventually, death, while leaving the mind intact. Almost 90 per cent of ALS patients die within two to three years of diagnosis, another 10 per cent can live much longer.

Granbois's symptoms began in November 1997, when she noticed weakness in one leg. Over a year, her walking deteriorated, she had more difficulty climbing stairs and eventually couldn't lift even a coffee cup with her hand.

"It was just progressive, a progression of symptoms that was just creeping along constantly. I could feel it every day. I knew I was dying. I could feel it," Elizabeth remebers.

Now the Hamilton woman is buying time -- slowing the progress of her disease by trying a a cocktail of AIDS drugs.

"I was going to be the guinea pig. It could be something that could prove fruitful for thousands of people," she says.

After two years on the medication, Granbois has been shocked to find that the inevitable slide to paralysis seems to have slowed down.
"I don't feel like I am dying anymore. My voice has come back. My left hand is not weak. It is as strong as my right," she says.

The treatment's effectiveness is encouraging news for her neurologist, Dr. John Turnbull, of the McMaster University Hospital's ALS clinic. But he wondered whether Elizabeth's case could be a fluke. A small percentage of ALS patients, such as physicist Stephen Hawking, can live with the disease for decades.

"Especially with someone who has had the disease for a couple of years like Elizabeth has, it's very unusual for them to go down and then improve," he says. "I think we logically assumed that the response we saw in Elizabeth is a meaningful response... what is less clear is whether it is applicable to other patients with the disease. That is why we are doing the trial now."

Turnbull has recruited 12 other ALS patients to see if the drugs will on work on them too. It's all part of a study at McMaster University that the medical community is watching closely.

"Anytime that we see even a glimmer that there may be reversibility for some causes for ALS, then I think we are ethically beholden to follow it up," Turnbull says.

The genesis of the idea came from a 2000 article in the American Academy of Neurology journal, Neurology. The article described how doctors noticed AIDS patients with symptoms like ALS were getting better on Combivir, Amprenivir, and Ritonivir, the drug cocktail that normally disables the AIDS virus, HIV.

Elizabeth's results seem to imply there may be a virus underlying this disease and that it may be reversible. One theory is that there is an underlying viral infection in patients with ALS and that that's why the AIDS drugs may work for ALS.

The second theory is that these AIDS drugs are somehow saving nerve cells that are programmed for some mysterious reason to die.

"Positive or negative, there is going to be some sort of offshoot of this that will be beneficial. It is going to help us understand things better," says Dr. Turnbull of the study that will be completed in eight months.

There are some drawbacks to the therapy. AIDS drugs are very expensive -- about $1500 a month, there are risks of serious side effects, no guarantees they will work, and the drugs are not a cure for the disease. But Grandbois has no regrets. While she may never be free of ALS, she hopes her gamble will pay off for thousands of patients.

To see a video news story produced by the CTV about Elizabeth, click the link below and look for the video link on the right sidebar:

CTV News Video: AIDS cocktail may bring hope to ALS patients 2:04