10:27 AEST Tue 18 Jun 2002
A Sydney neurologist has raised hopes of a new weapon against Multiple Sclerosis by combining drugs already used to fight the crippling disease.
The ABC's 7.30 Report on Monday night said four MS patients had experienced a turnaround in their symptoms after the new treatment by Dr Dan Milder.
Dr Milder was diagnosed with MS only two years ago and a rapid deterioration in her condition prompted her doctor to combine two medicines already in use against the disease.
"We didn't know what to do," Dr Milder told the ABC.
"There's nothing obvious to do, there hasn't been anything that is known to reverse progressive forms of Multiple Sclerosis and she was going down hill."
MS attacks the protective film around nerve fibres and stops communication between the brain and bodily functions.
Dr Milder believes his treatment helps regenerate the coating around damaged nerve and Natasha had a major improvement in her sight and mobility within months, although her condition had plateaued again.
Dr Milder tried the same treatment on three other patients with positive results.
"No one to the best of my knowledge has had a (treatment) series where consecutive patients have had significant, albeit partial, reversible deficits," he said.
A spokesman for the Australian Association of Neurologists did not dismiss the findings, but cautioned that more research and clinical trials were needed before MS sufferers could begin to get their hopes up for a cure.
KERRY O'BRIEN: Multiple sclerosis (MS) is a cruel and baffling disease, one that attacks the central nervous system, mainly in women between the ages of 20 and 40.
Its progress and severity are unpredictable, but at its worst it's a slow and painful road to paralysis and blindness.
We don't know the cause, and there's no cure.
So far medical researchers have been unable to progress beyond drug therapies which may reduce the severity of attacks, or slow the onset of MS.
Now, a Sydney neurologist believes he may have stumbled upon something promising.
Tracy Bowden reports.
DENISE BAGAN: She was happy, very active, lots of sports.
She wasn't a sickly child, at all.
It's devastating, and it's tragic.
You don't think it's ever going to happen.
TRACY BOWDEN: Just two years ago, Natasha Bagan was an active, healthy young woman with everything to look forward to.
But a shocking diagnosis changed all that.
NATASHA BAGAN: I had headaches and things like that, so I thought well, it must be something terrible.
Then he said, "Oh, I'm thinking it's MS".
I didn't know what that was.
But then on the other hand I thought Betty Cuthbert, and that's -- I cried.
TRACY BOWDEN: Sydney neurologist Dan Milder, Natasha's doctor, was disturbed by the unusually rapid decline in his patient's condition.
DR DAN MILDER, NEUROLOGIST: We didn't know what to do.
When I say 'we', she presented at a medical meeting and there was no consensus and there's nothing obvious to do.
There hasn't been any therapy that is known to reverse progressive forms of multiple sclerosis, and she was going downhill.
TRACY BOWDEN: Multiple sclerosis has affected Natasha Bagan's central nervous system, the brain and spinal cord.
Normally, messages pass along the body's nerves quickly, because the nerve fibres are insulated by a protective sheath called myalin.
In MS both the sheath and the cells that make it are attacked.
Eventually scleroses or scars are formed and the messages no longer get through properly.
DR DAN MILDER: It may affect balance, it may affect spinal cord function in the sense of strength, sensation, bladder control.
DENISE BAGAN: There had been a rapid decline.
He said to me -- well, my husband was told she would be in a wheelchair for the rest of her life, she would eventually have to go to a nursing home because there would be no way that we could look after her.
TRACY BOWDEN: Late last year, Natasha Bagan was admitted to hospital.
DR DAN MILDER: He was unable to walk without a person on either side.
Her vision had deteriorated very strongly.
There was an appointment made for her to see the royal Blind Society.
It was considered likely she was -- she would be functionally blind.
TRACY BOWDEN: Then Dr Milder took a chance on a new combination of two drugs already used in the treatment of MS.
DR DAN MILDER: She had been sensitive to steroids, to a form of cortisone and azathioprine is used as a steroid-sparing agent, so we thought we would try that.
It has been used in multiple sclerosis, but without very strong benefit, and so we thought we had to add another drug.
TRACY BOWDEN: Within weeks, Denise and Tony Bagan saw slight changes in their daughter.
Within months, a dramatic change.
Can you remember the first time you actually thought: there's something happening here?
DENISE BAGAN: The first time I realised something was happening is one night I went to the Prince Henry rehab and she was standing on the verandah waiting for me and I said, "Where's your wheelchair?"
and she said, "I don't use it any more, I walk."
And that was really exciting.
TRACY BOWDEN: Natasha Bagan's vision improved too.
NATASHA BAGAN: There was a time when even before I could only see black and white.
I was sitting in the lounge and I just said to mum, "Oh, I can see colour now".
TRACY BOWDEN: With Natasha Bagan's promising improvement, Dr Milder decided to introduce the treatment to other patients.
DR DAN MILDER: I thought it was likely to be significant, so a second patient was then started, who'd had the disease for 8 years, who'd been deteriorating strongly for the previous 4 years, and she also started to improve.
And then a third, and now a fourth.
TRACY BOWDEN: Dr Milder believes the treatment may allow the myalin around the nerves, damaged by MS, to regenerate.
Could it be a fluke, a coincidence, it's only a handful?
DR DAN MILDER: No-one to the best of my knowledge has had a series where consecutive patients have had significant, albeit partial, reversal of deficits.
TRACY BOWDEN: But the Australian Association of Neurologists urges caution until there's been further scrutiny of the treatment.
ASSOCIATE PROFESSOR, RICHARD MACDONELL, AUSTRALIAN ASSOCIATION OF NEUROLOGISTS: It would be, I guess, on the face of it, unlikely that the combination of those two drugs would produce a miraculous effect.
One would expect a modest effect at most, but as I say this observation needs to be subjected to proper scientific scrutiny, and it's certainly not disregarded but I guess placed in the appropriate context.
LINDSAY McMILLAN, MS SOCIETY VICTORIA: All these good ideas need to be tested.
But we can't deny the importance of letting people know that there are these potentially good news stories on the horizon.
TRACY BOWDEN: The next step is for clinical trials to be carried out.
Meanwhile, Natasha Bagan's condition seems to have plateaued.
She and her parents know the future is uncertain, but what they are certain about is what they see today.
DENISE BAGAN: We're excited about it.
I mean, I don't know how -- I don't know in the long run how she'll be.
I don't know how it will work.
But as far as I can see it should only just get better.
It's all hope.
KERRY O'BRIEN: Fingers crossed.
© 2002 ABC
TIME, JUNE 3, 2002
By DANIEL WILLIAMS
LATE LAST YEAR, SYDNEY Neurologist Dan Milder was running out of ideas on how to treat one of his multiple sclerosis patients. Diagnosed less than two years ago, "Samantha" was going down fast. Her vision was blurred and she was unable to see color; she was incontinent and incoherent, and her balance was so poor she was confined to a wheelchair. Milder had already advised her parents that Samantha, 28, might have to spend the rest of her life in a nursing home.
With no other goal than slowing her rate of decline-the best medicine could hope to do for Samantha's type of MS-Milder adjusted her drug regimen, combining a new MS drug with an older one. Her response stunned him. Within weeks, she was mentally sharper and her vision had improved. Within months, she was able to jog. Incredulous, Milder put another patient onto a similar program. Again the results were impressive. He tried it on a third, also with success. Last weekend, he presented his observations at a myology conference in Corfu, Greece. "Because of the dramatic and unexpected improvement in Milder's patients," says Byron Kakulas, Professor of Neuropathology at the University of Western Australia and one of the country's most distinguished medical researchers, "I support his recommendation that a controlled trial of the treatment be undertaken."
Of all the thousand natural shocks, MS is among the most dreadful. Most commonly striking women aged between 20 and 40, it stems from a betrayal by the victim's immune system, which attacks myelin, the protective sheath around nerve fibers. The myelin is replaced by plaques of hardened tissue which disrupt the transmission of signals to and from the brain and cause symptoms such as impaired vision, loss of balance and coordination, slurred speech, memory loss and, in severe cases, paralysis. Most patients start out with a type of MS called relapsing-remitting: after an attack they recover, either spontaneously or with the help of drugs-until the next attack. But about half of these patients go on, like Samantha, to develop progressive MS, in which remissions have never been demonstrated.
Indeed, many doctors consider them impossible, because they believe these patients have suffered not only myelin destruction but irreparable damage to the nerve fibers. Milder's observations challenge that view and may offer hope to many thousands of MS victims throughout the world.
But experts have learned to be skeptical. "MS has had many false dawns," warns Professor George Ebers, head of clinical neurology at Oxford University.
If Milder has made a momentous discovery, it happened largely by chance. When Samantha was in bad shape last November, Milder had her on a powerful MS drug-a new immunomodulator called interferon beta-lb-and steroids. But the program wasn't working. He considered prescribing an anti-cancer drug called mitozantrone, but this can damage the heart and Samantha's family said no.
He had to withdraw the steroids because they made Samantha psychotic. For a substitute, he settled on an immunosuppressant called azathioprine, which had been superseded a few years before as the top-shelf MS drug. Azathioprine can slightly increase the risk of cancer, so Milder prescribed a low dose. He also started Samantha on a different immunomodulator, glatiramer acetate-though in hindsight he regards that switch as unimportant.
Nearly two months later, Samantha visited Milder in his surgery. She was walking and seeing colors again. Her mother reported that the improvement had begun within days of starting the new treatment. "I was very surprised," recalls Milder, who immediately began researching whether these drugs had been used together before on people with progressive MS. He could find no record of it. "When she came to see me in April and I was told she was able to run half a kilometer, the significance of the whole thing began to dawn on me," Milder says. "I'm not aware of any [progressive MS] patient being able to run after a period-not of months, but years-in which they have been significantly unsteady."
Milder resolved to try the drugs on "Amy," 50. Her vision was poor and she needed a stick to walk. Sometimes her legs would "freeze," she says, and she'd stand on the spot until they came back to life. She was also, says Milder, "floridly disinhibited": brain disturbances had made her uncharacteristically effusive and tactless. Milder put her on azathioprine and interferon beta-lb.
Three weeks later he visited Amy at home. In the garden, he tested her vision with cards on which numbers are indistinct against a patterned background. Her score was higher than she'd achieved for years. Later, in her lounge room, she stood unsupported on one leg. "I'd never seen her do that in the eight years I'd been treating her," Milder says. He has also observed remarkable-and rapid-improvements in balance and mobility in a third patient, a 27-year-old woman.
The events spun Milder into turmoil. It seemed incredible that two drugs-routinely used together in relapsing-remitting MS- had apparently not been tried on patients with the progressive form of the disease.
HELP AT HAND? "MS is a nasty disease that robs people of a lot of their dignity," says Milder
More incredible to him was their apparent effect: they had "reversed deficit." The three women are not cured, he says, but they are better than he'd ever imagined they could be. "Everyone who knows her says they can't believe the improvement," says Samantha's mother. "She's our little miracle." Meanwhile, Amy's walking stick is folded up in a plastic bag in her bedroom, and she says she feels confident enough on her feet to cross the road between traffic.
Milder asked himself the necessary questions. Might these patients not have progressive MS? Had they previously been exaggerating their symptoms? Might their improvement be unrelated to the drugs? Was he seeing a placebo effect? Based on research, the patients' histories and his knowledge of the disease-built up over 20 years as a consultant neurologist-he confidently answered no to all of them.
Exactly why these drugs seem to work, Milder isn't sure. But he theorizes that the onset of progressive MS, rather than being an endpoint for worthwhile treatment, may in fact be a window for a more effective drug assault that gives myelin a chance to regenerate.
Perhaps, he speculates, the immune attack taking place in progressive MS is less ferocious than that in the relapsing-remitting form-and therefore easier to subdue.
Milder stresses that the treatment seems to do no more than suppress MS. (Samantha's improvement appeared to plateau after four months of treatment.) And where paralysis results from plaques on the spinal cord rather than the brain, the drugs almost certainly won't help. But if a clinical trial validates his discovery, the implications could be far-reaching. "It may be possible," Milder says, "by modifying doses and by various other permutations and combinations, to suppress the disease further."
Oxford's Ebers is open-minded. "I am of the view that everyone should
be listened to in these matters, especially when there is no effective
treatment for a disease. [Milder's] observations ... could form the basis
for further exploration." But Ebers' reference to false dawns is hard to
ignore. Usually," he says, "these are because of over- enthusiastic interpretation
of small numbers of patients in uncontrolled studies of short follow-up."
UWA's Kakulas is equally cautious, but believes "there is a sound neuropathological
basis for recovery in Dr. Milder's patients in the form of re- myelination."
A saving grace of MS is that it's not a fatal disease. Sufferers can wait
and see whether Milder's dawn is a real one."
Copyright © 2002 Time Inc