Richard K. Olney, MD, Founder of the ALS Treatment and Research Center at the University of California-San Francisco, has diagnosed amyotrophic lateral sclerosis (ALS) in over 1,000 patients since his residency in 1976 at the Oregon University Health Sciences Center in Portland.
But perhaps the most poignant diagnosis was the one he made when he determined that he had developed sporadic ALS himself in May 2004. That diagnosis was confirmed a few weeks later, in June 2004, by Catherine Lomen-Hoerth, MD, PhD, who has succeeded him as Director of the ALS Center. Since then, he has been busy speaking to the national media, using his own personal experience as researcher and patient to raise public awareness of this disease.
In March, Dr. Olney, 57, received a Public Education Award from the AAN Foundation honoring him “for sharing his personal experience with ALS to inform people everywhere about the disease.” Assisted by Paula, his wife of 30 years, and his adult children, Nick and Amy, he has told his story to People magazine, USA Today, the New York Times, “ABC World News Tonight,” CNN, “NBC Nightly News,” “Dateline,” the Los Angeles Times, and the San Francisco Chronicle. And he did a public service announcement for the ALS Association last September.
Neurology Today sat down with Dr. Olney and his wife one afternoon at their home in Corte Madera, CA, to discuss the state of ALS research and management, and his life as a patient and advocate for the disease. As his speech continues to deteriorate, this interview was scheduled as part of the last flurry of meetings he would have with the media. Paula, a kidney dialysis nurse, was there to interpret, and in some cases, she is quoted directly, based on her understanding of his views and circumstances.
WHEN YOU REALIZED THAT YOU, AS ONE OF THE LEADING ALS INVESTIGATORS, HAD ALS YOURSELF, WHAT MEANING DID YOU GIVE OF THAT COINCIDENCE?
Dr. Olney: Bad luck. I had often quoted the statistic in lectures that one in 1,000 people are struck at random during their adult life by ALS. Unfortunately, I had become one.
Paula Olney: I told him you're wrong. I wasn't going to believe it for one minute. He's too close to it. We had been jogging in Hawaii. We went on a 10-mile hike, biking, water aerobics. The only thing he couldn't do was play tennis.
WHAT GAVE HIM A CLUE THAT HE MIGHT HAVE ALS?
Paula: We thought we were dealing with a spinal cord injury until the spasticity jumped to his arms in May of 2004. He was lifting free weights and his right arm did not move smoothly. This told him that something was going on above the level of the disc.
Dr. Olney: I had been doing finger taps – tapping my index finger against my thumb. From August 2003, I could do 65 taps in 10 seconds, indicating a healthy neuromuscular system. By mid-May 2004, the number of taps I could do started to drop. Knowing that the only abnormality with extensive testing had been a mid-thoracic disc herniation prior to May, I became certain that I had ALS. The diagnosis was confirmed by Dr. Lomen-Hoerth in early June.
IS THERE ANYTHING YOU HAVE LEARNED AS AN ALS PATIENT THAT MAY BETTER INFORM THE WAY DOCTORS MANAGE OR TREAT THE DISEASE?
Dr. Olney: What I have learned basically reinforced my previous beliefs about the diagnosis and management, particularly the way we do it at UCSF. We treat everyone with a lot of compassion, and respect everyone's autonomy. So if we have a treatment to recommend, we tell the patients the advantages and disadvantages and let them decide.
Paula: The available therapies are designed to make the patient comfortable to live the life he has left. There are many drugs that can treat symptoms, which in his case include spasticity and bladder urgency. There's also quinine for muscle cramps, which he doesn't have. He takes drugs for spasticity and bladder problems and a low dose antidepressant, as well as riluzole (Rilutek). Lots of people benefit from psychotherapy and supportive relationships.
Dr. Olney: I never felt really depressed, but a low-dose antidepressant helps me get more enjoyment out of every day.
Paula: And he takes antioxidant vitamins and co-enzyme Q10.
WHAT ADVICE DO YOU HAVE FOR NEUROLOGISTS?
Dr. Olney: Be open and honest about the possibility of ALS, when you strongly suspect it. But never give the diagnosis with certainty until all the testing is done. Preferably, the certain diagnosis should be given by the neurologist who will provide long-term management.
ARE NEUROLOGISTS DOING OKAY IN THEIR MANAGEMENT OF THE DISEASE?
Dr. Olney: Yes, especially neurologists who manage ALS as a specialty. For neurologists who do not treat ALS (as a specialty), it's probably advisable to mention ALS only as a possibility, and to refer them to an ALS center or specialist for confirmation. Allowing the ALS specialist to form a relationship with the patient and his family while other diseases are being ruled out helps to soften the blow when the diagnosis is confirmed.
Paula: Lou Gehrig was alive in the 1930s – he died June 2, 1941 – and there's still nothing to slow it down significantly.
IN THE NEW YORK TIMES ARTICLE, YOU SAID THAT IN THE EARLY 1990S RESEARCHERS WERE OPTIMISTIC THAT A TREATMENT COULD BE DEVELOPED BASED ON WHAT WAS KNOWN. WHAT HAPPENED?
Dr. Olney: There was great optimism that treatment with neurotrophic factors would significantly slow down the disease. Also, the first cause of ALS was discovered in 1993. Twenty percent of the 10 percent of patients who have familial ALS have mutations of SOD1 gene. When that gene was put into mice to make transgenic mutant mice, we had an excellent model to study. Based on that, we have discovered many molecular mechanisms that play a role in the development of ALS. Many people have been surprised at how complex the disease mechanisms are, because treatments of most known mechanisms have produced only modest results.
Based on research in transgenic mutant mice, minocycline is currently in a phase III trial. However, other treatments that did work in the mouse model have not worked in people, such as the negative human results with celecoxib (Celebrex).
WAS THE MOUSE MODEL NOT EFFECTIVE?
Dr. Olney: It has not been as effective as most of us thought in the early 1990s.
ARE THERE ANY PROMISING TREATMENTS IN THE PIPELINE?
Dr. Olney: Treatments that are currently in the pipeline are expected to at most, slow down the disease and not be a cure.
YOU SET UP A DRUG TREATMENT TRIAL AT UCSF, WELL BEFORE YOU EVER SUSPECTED YOU WOULD HAVE ALS, AND YOU CHOSE TO BE BLINDED TO WHETHER YOU WERE TAKING A DRUG OR PLACEBO. DO YOU KNOW YET IF YOU ARE ON A PLACEBO?
Dr. Olney: No, I don't. The trial is set up so that people are in one of four groups. One group is ritonovir, low dose, another is ritonovir, high dose, one group is hydroxyurea, and the fourth group is placebo. These two drugs – hydroxyurea and ritonovir – are the ones that have been most promising in the drug screening program of the Newton, MA-based ALS Therapy Development Foundation. They've screened over 100 FDA approved drugs to look for ones that might help slow ALS. The founder's brother has ALS.
The trial started in January, and I'm the first patient to enroll. It's a phase I/II. We are expecting to enroll 60 patients.
WHAT MOTIVATED YOU TO ENTER YOUR OWN TRIAL NOT KNOWING WHETHER YOU WERE TAKING A PLACEBO OR A DRUG?
Dr. Olney: The only way we will ever know if drugs are effective is to have placebo control trials, so I wanted to make a statement with my behavior to reinforce this. With this trial, I will only possibly be on a placebo for six months. At the end of six months, I can choose which drug I want to take.
Also, all treatments under investigation currently are thought to at best slow the disease. If one of them were likely to cure ALS totally, then it would be much harder to take part in a placebo-controlled trial. With every drug trial that is being planned that is not the case. Once we have three or five drugs that slow it down, maybe the combination will more markedly arrest progression.
YOU'VE ALSO DECIDED NOT TO USE A VENTILATOR. WHY?
Dr. Olney: The first thing everyone should think about before going on a ventilator is “What will your quality of life be?” I don't think the quality of my life would be sufficiently good that I would want to live for years on a ventilator.
Secondary considerations are practical. The burden of care is heavy on the family or the cost is great. It might cost $200,000 to $300,000 a year to maintain.
ARE VENTILATORS WIDELY USED AMONG ADVANCED ALS PATIENTS?
Dr. Olney: About five to 10 percent go on ventilator. In my experience, about half of those only choose to stay on a ventilator for a few months. Many of these people still have good function of their arms or their voice; then when they lose this function, they chose to withdraw ventilation. The other half who stay on a ventilator for years usually have a specific goal in mind, such as seeing a child graduate.
WHAT ARE YOUR THOUGHTS ABOUT THE DIRECTION OF RESEARCH NOW?
Dr. Olney: I think we're going in the right direction. Within a year or two, the use of viral vectors to introduce genes in the body to stimulate production of neurotrophic factors is likely to help the motor neurons stay healthy longer. The first trial will likely start at Johns Hopkins and be led by Jeffrey Rothstein, MD, Director of The Robert Packard Center for ALS Research. They will be introducing insulin-like growth factor-1.
In the 1990s, there were a number of trials of neurotrophic factors, administered by subcutaneous injection. It's not clear that the neurotrophic factor reached the neurons. Ever since (the attempts with) the subcutaneous growth factors, I have been telling my patients that I expect viral vectors will be developed to introduce neurotrophic factor to the brain, and I have long expected that this approach would come to trial long before stem cells.
This approach shows more promise sooner than stem cells. Maybe in five or 10 years, stem cells will be very helpful to treat ALS.
WHAT IS THE QUALITY OF TREATMENT THAT ALS PATIENTS RECEIVE AROUND THE COUNTRY?
Dr. Olney: I think we're doing well with patients who have access to ALS centers, but unfortunately, the majority of ALS patients in the US are too far removed geographically to have access to ALS centers on a long-term basis. Most are taken care of by primary care physicians and less likely to receive the drugs for treatment of symptoms as well as all the non-medical treatments available.
In our ALS center, patients are typically seen by nine people, usually once every three months. These include the neurologist, an ALS nurse, speech pathologist, dietician, respiratory therapist, physical therapist, occupational therapist, social worker, and assistive technology specialist.
In the US, there are 20 or 30 ALS centers, all well known around the world.
ARE YOU STILL INVOLVED WITH THE ALS CENTER?
Dr. Olney: I'm still writing papers, but slower, one letter at a time. I received a three-year grant from the ALS Association in the summer of 2004, to start my most important research project. This project is starting to collect data about environmental and genetic interactions, which I believe are the likely explanation for what causes sporadic ALS. I turned it over to Cathy, but I am still working on the project.
LOOKING BACK AT HIS CAREER, WHAT ARE HIS ACCOMPLISHMENTS HE IS MOST PROUD OF?
Paula: Receiving the Golden Toe Teaching Award from the neurology residents at UCSF, founding the ALS Center at UCSF, and getting the Public Education Award of the American Academy of Neurology Foundation.
AAN FOUNDATION AWARDS PUBLIC EDUCATION AWARD TO RICHARD OLNEY
SAN FRANCISCO—NBC cameras were on hand to record the event. Eighty school children from the area had sent a rousing message of support, and representatives from the AAN and AAN Foundation had traveled from New York, Houston, Oshkosh, WS, and Minneapolis to be there.
Stanley H. Appel, MD, a former recipient of the Shirley E. Essey Award for ALS Research, had come from Baylor College in Houston, TX, where he is a Professor and Chair of Neurology. AAN Foundation Chair Kenneth M. Viste, MD, was there along with AAN Foundation Executive Director Martin Schaefer; Richard Essey, a trustee of both the AAN Foundation and ALS Association; and Catherine Lomen-Hoerth, MD, PhD, a former student of Richard K. Olney, who is now Director of the University of California-San Francisco ALSA ALS Center.
They joined family members, friends, and neurologists from UCSF to honor Dr. Richard K. Olney here on March 20 when he was presented with the AAN Foundation Public Education Award.
In a presentation to Dr. Olney, Lewis P. Rowland, MD, Professor of Neurology at Columbia University, Editor-in-Chief of Neurology Today, and a AAN Foundation trustee, said: “There have been published reports of a few physicians who were struck with this disease – and we have known the spouses of some neurologists who have had it. But never before has a neurologist been affected and then used his own condition to inform people everywhere what a challenge it is, why research is so important, and why we all believe that sooner or later we will be able to cure or prevent ALS.”
Dr. Rowland noted that the Foundation Board selected “public education” as the basis for the award to Dr. Olney, because of the role he had played in publicizing the disease and his own condition.
Among his efforts, Dr. Rowland said, Dr. Olney has informed people about the need for placebos in trials of new drugs, the process used for selecting candidate drugs, the role of the FDA, and the availability of drugs approved for some other purpose to be used ‘off-label’ for ALS.
In addition, he said, directing his remarks to Dr. Olney, You have not been bashful in explaining the need for the public to give money to support your own or other ALS research and patient care centers. You have explained the importance of advance directives in dealing with the dilemma of tracheostomy and chronic mechanical ventilation. Your vigorous actions have proven to be effective antidepressants.
“We congratulate you with this award. We know that you know the need to accelerate research, and we know that you know how many brilliant young scientists have entered the fray against ALS.”
In accepting the award, Dr. Olney said: “I am deeply honored to receive this award for Public Education from the American Academy of Neurology Foundation. I will especially treasure this award, because I am receiving it from esteemed colleagues across the nation.”
The inscription on the plaque to Dr. Olney reads: “The American Academy of Neurology Foundation proudly presents this Public Education Award to Richard K. Olney, MD, for sharing his personal experience with amyotrophic lateral sclerosis to inform people everywhere about this disease. With better information, sponsors of research can hasten the day when the disease can be prevented, ameliorated, or cured.”
The award presentation was videotaped and shown in April at the AAN Annual Meeting in Miami.