On Friday, March 23, the ALS Association presented Raymond P. Roos, MD, with a grant for $150,000 over three year to support multidisciplinary care for patients with ALS at the University of Chicago’s ALS/Motor Neuron Clinic. Roos, who has been director of the clinic for almost 20 years, says the money will continue to fund the clinic’s multidisciplinary services to help patients and their families cope with the disease. In addition to providing a clinical evaluation, the clinic provides physical, occupational and speech therapy, nutrition counseling, speech and swallowing guidance, and help with assistive devices like wheelchairs and braces.
ALS (amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease after its most famous patient) is a disease of the nerve cells in the brain and spinal cord that control voluntary muscle movement. It causes progressive weakening of the muscles that leads to difficulty walking and moving, and is usually fatal once it significantly weakens the muscles in the chest that control breathing. ALS affects about one in 20,000 people worldwide, and while there are some treatments to lessen the symptoms, there is no cure.
When I interviewed Roos, he had just received a note from the family of a former patient that underscored the poignancy of treating ALS patients: It was accompanied by a funeral announcement. Roos said that while he doesn’t expect to find a cure for ALS soon, he does believe that in a short time research will lead to treatments that can improve the quality of life after diagnosis, and even extend it. Flanked by towering bookshelves and a poster of Gehrig, we spoke about the current state of treatment for ALS, developments in research, and his work in the ALS Clinic.
What are the treatment options right now for patients with ALS?Treatment falls into three groups. One group, which is unfortunately the smallest, has to do with drugs that slow down the disease. There’s only one drug that is FDA-approved, riluzole, that does this. The good news is that it slows down the disease. The bad news is that it has a very small effect, and it’s somewhat of an expensive drug. The best trial showed that it slowed down the disease by only three months compared to placebo, with no improved quality of life. The FDA approved this drug on that basis just because ALS is such a desperate disease, with the hope that other drugs would follow. But it’s been over ten years since riluzole was approved and unfortunately we have no other drug that slows down this disease.
The second treatment approach I would call “symptomatic.” We have a lot of symptomatic treatments in medicine. For example, we don’t cure high blood pressure or diabetes, we just treat them. There are a variety of symptomatic treatments for ALS that we use. For example, ALS involves progressive weakening, leading to problems with ambulation. For that we would provide appropriate walking assists—a brace on the ankle, or a cane or a walker, or a wheelchair or electric scooter. We evaluate the patient and make the appropriate recommendations. Patients have progressive problems swallowing and frequently that necessitates putting in a feeding tube. Patients have progressive speech problems, so we make recommendations regarding a communication device. Patients have progressive difficulty breathing, which is the life-threatening aspect of ALS, and we make recommendations with respect to what’s called BIPAP (bilevel positive airway pressure), which would be a mask that patients use, usually in the evening, to assist with breathing. About five percent of patients decide to have a tracheostomy and a ventilator . So there are a variety of symptomatic treatments we can make available, as well as provide guidance and fulfill an educational role.
The third treatment approach has to do with experimental clinical trials. There’s a very well organized community of academic medical centers that perform clinical trials for ALS. For example, there was just a clinical trial sponsored by Biogen Pharmaceuticals that involved over 800 ALS patients internationally, and there are perhaps 10 other clinical trials going on right now in ALS, of varying size.
What’s the history behind the ALS Clinic at UChicago?
The University of Chicago has a very long history of care for ALS patients, including a multidisciplinary clinic. One of my former colleagues, Dr. Jack Antel, started a multidisciplinary clinic over 25 years ago, probably one of the earliest ALS clinics in the United States and perhaps even the world. So we have a very long tradition. Initially the clinic was funded by a National Institutes of Health program project grant, and then the Muscular Dystrophy Association funded it for a short time. Now we’re about to reboot the clinic as a result of this support from the ALS Association.
How long have you been working with ALS patients?
When Dr. Antel left this institution, I took over as director of the clinic. In some ways I was reluctant to do so because I realized that ALS was not a treatable disease. However, I actually ended up finding it to be a very satisfying experience. In many ways, as a result of this disease not being curable, one’s role as a physician in guiding and treating the patient and family is more frequent and necessary than in other neurological diseases that are much more treatable. There are a number of extremely important issues, such as end of life decisions, which make one’s role as a physician an especially critical one in dealing with these patients. Although I was reluctant to take over the directorship initially, I’ve found it to be the most satisfying experience of my physician career.
What are some of the recent breakthroughs in research on ALS?
Our major understandings of ALS have come through studies of inherited ALS. About 10 percent of ALS is inherited, which is true in a number of neurodegenerative diseases. The identification of the genes that cause the inherited form of the disease has opened up a window of understanding. In the case of ALS, new research breakthroughs in the last year have demonstrated that the RNA form of a particular gene is toxic. Just as a reminder, the DNA of the gene makes RNA that is complementary to it, and the RNA makes protein. We generally think of diseases as being caused by mutations in the protein, but the insight over the last few years in ALS is that the RNA may be toxic, that it’s a mutated form of RNA rather than the protein that leads to the death of motor nerve cells. These are unanticipated insights into ALS. Over five years ago nobody would have thought that RNA had anything to do with ALS.
Has the outlook for ALS treatment changed very much in your time?
The answer is still not clear. I am hopeful that the fact that we think toxic RNA plays a role in ALS provides not only insight into understanding what causes ALS, but how to treat it. I say that because there are a couple of other diseases in which we think toxic RNA causes the disorder, and sophisticated powerful molecular biological technologies are being tested for treatment of those diseases. Similar kinds of technologies and approaches are in the works for ALS, so I’m hopeful about this. In my lab we are investigating transgenic mouse models of ALS to see if we could employ genes and drugs to prolong survival in these mice, and then take those treatments to patients.
Are those treatments for extending life, or is there potential for a cure?
Are we going to hit a jackpot and produce a cure? I don’t think that we’re going to have the magic bullet soon that will cure patients. I think we probably have to walk before we run—and find some effective treatment before we can talk about a cure. Most of us feel that treatment of these neurological diseases is going to be like cancer treatment, in which we will need more than one drug and varying protocols to prolong life, and to provide a good quality of life. If we could slow things down in my lifetime I would be excited and happy. I think once we do that we’ll be able to use these insights into showing the way to achieve additional effective therapies. In other words, one good hit can snowball, and we’ll be able to make a variety of effective drugs building on the same therapeutic target. I’m optimistic about the future of ALS.
Dr. Roos also spoke to the Chicago Tribune recently about the outlook for ALS treatment and research.