MDA/MDAC GROUP PREPARES FOR COMBINATION ALS DRUG TRIALS
On May 3 in Chicago, MDA sponsored the inaugural meeting of the MDA/MDAC Physician's Group on ALS, a united effort by MDA and the Muscular Dystrophy Association of Canada to encourage drug companies and academic researchers to join forces to conduct clinical trials of ALS drugs in combination.
MDA and MDAC are committed to the notion that for amyotrophic lateral sclerosis (ALS), as with cancer and AIDS, an effective treatment may be found through the combined use of drugs that have limited value when used alone.
Representing MDA were its Director of Science Technology Donald Wood, who served as the group's chairman, Medical Advisory Committee Chairman Dr. Leon Charash, and Scientific Advisory Committee Chairman Dr. Rodney Howell. Appearing for the MDAC was Dr. Michael Brooke, president of that organization.
"The concept of combination trials in ALS is exciting but presents many challenges," MDA's Wood said. "We need to focus on overcoming the proprietary interests of pharmaceutical companies, and persuading them not only to provide quantities of drugs under development but also to yield a measure of control to the impartial scientific body represented by our Physician's Group.
" Leading ALS clinicians and researchers who belong to the Physician's Group on ALS include Dr. Robert Brown of Massachusetts General Hospital in Boston, Dr. Hiroshi Mitsumoto of the Cleveland Clinic Foundation, Dr. Steven Ringel of the University of Colorado Health Sciences Center in Denver, Dr. Jeffrey Rothstein of Johns Hopkins University in Baltimore and Dr. Teepu Siddique of Northwestern University Medical School in Chicago.
The Physician's Group, which will meet again in the next few weeks, formed subgroups to create a structure for the furthering of combination trials, to establish a liaison with drug companies, and to get reports on the current state of ALS research to researchers, physicians and people affected by the disease.
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 JOURNAL ARTICLE TELLS MORE ABOUT RILUTEK TRIALS
A long-awaited explanation of the 959-patient trial that was crucial in winning approval for Rilutek (riluzole) for ALS was published in the May 25 issue of the British medical journal The Lancet.
The U.S. Food and Drug Administration approved Rilutek for the treatment of ALS in December 1995.
MDA researcher Jeffrey Rothstein at Johns Hopkins University in Baltimore said the FDA had the information contained in the Lancet article when it made the decision to approve Rilutek. Now that the report has been published, physicians everywhere can review the same data.
"Since January, when Rilutek first became available by prescription, patients and doctors have wanted to see the data that prompted the FDA to authorize expanded access to the drug," said Dr. Leon Charash, chairman of MDA's Medical Advisory Committee.
"Rilutek is the first drug ever shown to benefit people with this condition, and today's study elevates it to a level that obliges us to use it as the control for combination drug trials that likely will foster major health benefits for people living with this progressive disorder," Charash said.
After 18 months of treatment with either Rilutek or a placebo (sham drug), 50.4 percent of patients receiving placebo were still alive without tracheostomies, compared with 56.8 percent of those on riluzole.
According to the study, a dose of 100 milligrams a day appears to be the best benefit/risk compromise, compared with 50 milligrams (fewer side effects and less benefit) or 200 milligrams (more side effects and slightly more benefit).
Side effects of Rilutek include fatigue, nausea, decreased lung function, headache and elevated liver enzymes.
A buildup of the central nervous system chemical glutamate is thought to contribute to the progress of the disease, and Rilutek, manufactured by Rhone-Poulenc Rorer, is thought to counteract this buildup. MDA grantee Rothstein is a leading authority on glutamate and ALS.
The trial reported on in The Lancet was conducted at centers throughout the United States and Europe. All the U.S. centers were MDA-supported clinics or MDA/ALS centers — Baylor College of Medicine in Houston, California Pacific Medical Center in San Francisco, Johns Hopkins School of Medicine in Baltimore, Northwestern Medical Center in Chicago, and Tufts/New England Medical Center in Boston.
Charash pointed out that MDA is the largest nongovernmental sponsor of scientific research seeking treatments or a cure for ALS. The Association invests more than $5 million annually in ALS research and medical services ($100 million since the 1950s).
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CEPHALON, CHIRON SEEK APPROVAL FOR MYOTROPHIN
On June 7, the drug company Cephalon and its partner, Chiron, will meet with the Food and Drug Administration to seek approval for the drug Myotrophin (IGF-1) as a treatment for ALS.
In January, the FDA denied the companies permission to begin an early access program (limited free distribution program for a drug not fully approved by the FDA) for Myotrophin and asked them to supply more information. In April, the FDA granted them permission to resubmit the application for Myotrophin.
It isn't certain whether the outcome of the June 7 meeting will, if favorable for Myotrophin, result in an early access program or a more traditional New Drug Application (NDA), the first step toward full approval of the drug for sale by prescription.
Some of the questions that have delayed a hearing on Myotrophin apparently deal with the drug's safety.
Cephalon has set up a number, (800) 797-0705, to call for updated information about Myotrophin.
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PHYSICIAN WITH DYSTROPHY CAN RELATE WELL TO HIS ALS PATIENTS
Dr. William Herzberg is a neurologist in Vancouver, Wash., who treats patients with a variety of neuromuscular conditions, including amyotrophic lateral sclerosis.
What sets Herzberg apart from most physicians is that, since his teens, he himself has been affected by a neuromuscular disorder, facioscapulohumeral (FSH) muscular dystrophy. The disease has initial onset in the face and shoulder area and generally has a slow progression.
*** Are Your Patients Aware That You Have A Neuromuscular Disease?
Yes, it's pretty obvious, especially when I'm walking or when I'm doing an exam and moving all around a patient.
*** How Does Your FSH Dystrophy Affect Your Interactions With Patients?
It's a positive thing. I think that the patients with neuromuscular diseases who see me find it easier to work with a physician with some experience of what they're going through.
*** Why?
Patients in general approach a doctor in a position of vulnerability. They're naked or near naked, they're ill, they need somebody else's help. Their body is betraying them. In walks the young doctor who appears invincible in the clean white coat, and they may wonder how that person can relate to what they're experiencing.
The patients can see that I'm dealing with problems, maybe not as big as theirs, but they can see that. That breaks down some walls.
*** How Did You Become Interested In Treating Neuromuscular Diseases?
When I was a medical student, I went to see Dr. Robert Miller as a patient. I had been seen by a lot of prominent neurologists, including Dr. Lewis Rowland at Columbia, and now I wanted to be seen by Dr. Miller in San Francisco. Meeting him sparked an interest in treating neuromuscular diseases, an interest that came naturally to me because of my dystrophy.
I was chosen to do a fellowship with Dr. Miller following a residency. I worked with him on the CNTF (ciliary neurotrophic factor) trial for ALS. It was an invaluable experience, although the trial wasn't successful. (Both Miller and Rowland are MDA- funded researchers and directors of MDA ALS research and clinical care centers. Evidence of toxic side effects and a lack of therapeutic effect caused CNTF trials to be stopped.)
Now I'm in practice, working with four other neurologists, and I'm the one who takes the neuromuscular cases. I see a variety of cases, muscular dystrophy, spinal muscular atrophy, and I have a little group of ALS patients.
*** Are Your ALS Patients Taking Rilutek?
Yes, and they're tolerating it.
*** What Does It Mean To Patients To Have An Approved Treatment?
It means an awful lot, even if the amount of time you're buying is not great. (Rilutek has been shown to somewhat prolong survival.) I remind patients that, had they come to see me five years ago, I wouldn't have had anything to offer them in terms of treating the disease. To have ALS in this day and age is emotionally very different than it was five years ago.
*** What Do You Want To See Happen In ALS?
I would like to see earlier diagnosis — treating the disease before many of the motor neurons have died. I think this will be important, in addition to the preservation of the remaining motor neurons.
With regard to treatments, I'm very hopeful about drug treatment for ALS, and I encourage my ALS patients to enter drug trials.
I think we're going to be seeing a lot more things coming down the pipeline. There are just so many ideas now emerging that the momentum is not going to slow down.
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IT'S GOOD TO KNOW YOU'RE NOT ALONE
David Moore and Carol Ann Cooke were once eighth-grade sweethearts in Lubbock, Texas. They grew up, left Lubbock, and met and married other people. They each had two children and later divorced their respective spouses.
Some 34 years later, in Dallas, David and Carol Ann re-encountered each other and, soon after, they married. Tragically, Carol Ann died of ALS this year.
David Moore says of his late wife: "She had the softest, most beautiful brown eyes ever. Even when she could no longer talk or smile, she could smile at me through those eyes, to the very end."
Shortly after Carol Ann's death, David Moore wrote this letter to Anita Stephenson, MDA's district director in Dallas.
Dear Mrs. Stephenson:
My wife, Carol Ann, had the unbearable misfortune of ALS. She was diagnosed March 3, 1995, and died Feb. 26, 1996.
During the hopeful times, the times of anguish, and the times of terror, the members of your staff, and of the Neuromuscular [MDA] Clinic at the University of Texas Southwestern Medical Center provided caring, professional and courteous service.
Susan Newton [program service coordinator], Dr. Wilson Bryan [MDA clinic co-director] and Debbie Aulenbacker [research nurse] of the Neuromuscular [MDA] Clinic made the horrible journey somewhat bearable. If there is a Medal of Honor in medicine, each of these people and their staff deserves one. Sincerely, David R. Moore
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ALS PATIENT HELPS OTHERS TALK ABOUT IT
"It Helps to Talk About It" is a book by the late Bob MacLean about his personal head-on confrontation with ALS. His words are directed to people with ALS or anyone else interested in learning about this disease and its drastic effect on lives.
MacLean effectively educates without the use of dry, technical jargon. Instead, his provocative insights and strong sense of humor get the point across. It Helps to Talk contains many tips about dealing with your emotions (those of loved ones and caregivers, too); methods of informing people everywhere about ALS; how to maintain independent living and a healthy mental attitude; where to get help; and much more.
However, his number-one reason for writing the book is to show that talking about the disease is the very best thing you can do. "Get it out in the open early," says MacLean. "It's the most valuable weapon against denial and depression.
" Sadly, Bob MacLean died after a long and courageous fight against ALS before the manuscript was printed in final form. He'll be missed by many, but his wisdom will continue to help many people with ALS and others with disabilities for a long time. If interested in reading MacLean's book, contact a local MDA office and borrow a copy.
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ALS GIVES MUSICIAN A NEW PERSPECTIVE
The cover of Jason Becker's compact disk shows an electric guitar in the lower left-hand corner. In the lower right is a wheelchair. Those are the emblems that have defined his young life and his music.
Becker began playing guitar at age 3 and recorded his first album at 15. At 19, shortly after being hired as David Lee Roth's lead guitarist, he received a diagnosis of ALS.
Now 26, Becker has issued "Perspective," consisting of eight songs he wrote and one by Bob Dylan. In his home studio, he used a computer set-up to compose his songs. His music was then transformed by a production team under his direction into a recording including live musicians.
The imaginative selections draw from a variety of musical styles and use such instruments as a bamboo flute, rain stick and synthesizer in addition to traditional instruments. Guitar and keyboard tracks by Becker form the centerpieces of six of the songs. Some of these tracks were recorded in earlier years, and others as his dexterity declined.
Becker's well-produced album features some prominent guest performers, including Steve Perry of Journey and guitarists Michael Lee Firkins and Steve Hunter.
Becker comments that ALS "has crippled my body and speech, but not my mind." Loss of his playing ability allowed him to perceive music differently and added a new vision to his compositions. To continue composing, he's devising a new computer system that responds to eye movements.
The album, and an accompanying music video, are available from: Jason Becker, P.O. Box 5109, Richmond, CA 94805. Jason can also be heard on Roth's 1991 album, "A Little Ain't Enough," and on Cacophony's "Speed Metal Symphony" and "Go Off."
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EMGs AND DIAGNOSIS
From "Ask the Experts," on the MDA Forum on CompuServe. "GO MDA."
Q. I would like to know if EMGs (electromyograms) done on the limbs of the body can detect a bulbar onset of ALS (early appearance of symptoms in the throat and mouth muscles). If not, what test can and should be done to check for a bulbar onset? Also, how important is a muscle biopsy in the detection of ALS if EMGs appear normal?
A. From Dr. Robert McMichael, MDA clinic director, Ft. Worth, Texas: If the limb EMG is characteristically abnormal, it helps establish the diagnosis of bulbar-onset ALS. A tongue EMG, if abnormal, strongly supports the diagnosis, if alternate diagnoses such as brainstem lesions are excluded.
A. From Dr. Mark B. Bromberg, MDA clinic director, University of Utah, Salt Lake City: In making the diagnosis of ALS, the site of onset is less important than the distribution of lower and upper motor neuron damage. The EMG is a sensitive technique for detecting lower motor neuron damage in body regions that are not yet weak. Thus, abnormalities in the EMG can be used to help make the diagnosis of ALS early on when there is only weakness of bulbar muscles.
One advantage of the EMG is that it can be applied to a number of different muscles and is far less invasive than a muscle biopsy. If an alternative diagnosis is in question, sometimes a muscle biopsy can provide specific information.
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