Early Diagnosis of ALS Benefits Patients, Research
“In terms of quality of life, our goal is to allow patients to do meaningful things on a day-to-day basis,” said Barrow Neurologist Dr. Shafeeq Ladha. “We want them to be able to lead as normal a life as possible with as much independence as possible, as well as keep them as comfortable as possible.”
Dr. Ladha is the director of the Gregory W. Fulton ALS and Neuromuscular Disease Center in Phoenix and, in that capacity, coordinates care for patients of the center, which often includes access to clinical trials and optional participation in basic science research.
The center is staffed by neurologists; physical, occupational, respiratory, and speech therapists; a social worker; and a nutritionist. The center also partners with providers at other sites, such as cardiologists and pulmonologists who have knowledge of neuromuscular diseases.
Dr. Ladha said another benefit of being part of an ALS clinic is that the providers have a lot of experience with the disease.
“Your providers have just worked with it more, and I think that’s a big advantage over just seeing someone in the community who has a couple of ALS patients,” he said.
The Challenges of an ALS Diagnosis
According to Dr. Ladha, the variability in symptoms and disease progression is one of the reasons ALS can be difficult to diagnose.
“It always presents with weakness, but the weakness can be anywhere in the body,” he said. “It can start out in the leg, arm, swallowing, speech, or breathing muscles. The progression, likewise, is quite variable. I’ve seen patients pass away within six months of symptom onset, and I’ve seen patients who have symptoms and are still alive 20 or 30 years later.”
Barrow Neurologist Dr. Jeremy Shefner, whose research is focused on biomarker development and the clinical therapeutics of ALS, said that depending on the severity and the body part affected, muscle weakness does not concern some people initially, particularly older people. Because of that, they don’t see a doctor as early as they should.
When people do see a doctor, they are often diagnosed with a less severe problem that shares symptoms with ALS.
“I think most of the medical community doesn’t recognize the disease,” Dr. Ladha said. “It doesn’t have a pattern that they can quickly latch onto. In the early stages, it can be mimicked by a lot of other diseases. If you start to get weakness in your hand, the first thing most people think of is carpal tunnel syndrome or a pinched nerve in the neck. It’s not until it doesn’t fit with carpal tunnel or a pinched nerve that the patient is referred to someone else.”
Dr. Shefner said primary care doctors usually only see one to two ALS patients in their entire career, so the disease is not foremost on their minds.
On average, ALS patients are diagnosed a year after their first symptom and survive about 30 months after diagnosis, according to Dr. Shefner.
“So, the first 12 months of the disease are significant,” he said.
Dr. Ladha said that the Fulton ALS clinic at Barrow sees about three to four new ALS patients each week and follows about 200 to 250 patients at any given time.
Some people with familial ALS can be diagnosed before they even experience symptoms. An estimated 10 to 15 percent of people with ALS have a family history of the disease.
“There are a handful of genes that are testable, and if you test all the genes, you will probably pick up about 70 percent or so of patients with familial ALS,” Dr. Ladha said.
Dr. Shefner said there is also a test available for a gene mutation that has been found in a fair number of sporadic ALS cases.
However, people do not always choose to undergo genetic testing, possibly because their insurance does not cover it or they do not want to know they have the disease.
“If there is no treatment for it, would you really want to know? If you’re going to get it, you’re going to get it, regardless,” Dr. Ladha said. “There are some things that are changing, though. We have a study coming up that actually is going to treat a very specific gene mutation. So, if we have treatments for familial ALS, then there is something to gain by getting tested.”
ALS Clinical Trials
Dr. Shefner said Barrow has a role in almost every ALS clinical trial conducted in the United States.
“We’re also doing a lot of basic science and biomarker research as well,” Dr. Ladha said. “There’s probably about eight or nine studies patients can be a part of right now. It changes from month to month, but we always have quite a few options for patients, depending on their willingness and desire.”
However, most ALS clinical trials have criteria for enrollment, often requiring participants to have been diagnosed less than two years prior to starting the trial, according to Dr. Shefner. He said patients who have had the disease for two years or longer are usually ineligible for other reasons.
“For instance, if your breathing function declines past a certain point, then you’re excluded from the trial,” Dr. Ladha said. “It just makes the study a lot harder to do and reduces the chances that we’ll find the positive effect of that drug.”
Dr. Ladha and Dr. Shefner said there are a few different motivators for ALS patients to enroll in clinical trials. One reason is the possibility that the drug might actually work for the participants, and another is that it might help future ALS patients.
I’m pretty optimistic that we’re going to find something that will help with this disease in the next several years.
-Dr. Shafeeq Ladha, Barrow Neurologist
“It’s the only way we’re going to treat people long term,” Dr. Shefner said. “When properly explained and made clear to people that they are being a meaningful participant, it can be an invigorating experience.”
Dr. Ladha said participating in a clinical trial also has psychological benefits because participants are able to regain a sense of control.
“You have this disease that takes all of the control out of your life, which is a really frustrating thing for these patients,” he said. “When they are part of a trial, they can say, ‘I’m actively doing something against this disease instead of just sitting here and letting it take me.’ ”
Promise for the Future
Dr. Ladha and Dr. Shefner said there are a few ongoing trials that appear to be promising.
Dr. Shefner is the global principal investigator for the only current phase-three ALS study worldwide. In a phase-three study, the U.S. Food and Drug Administration determines whether or not to approve the drug. This particular drug targets muscle rather than nerves, increasing the efficiency of muscle contractions to counteract weakness. ALS patients’ muscles gradually waste away because the disease causes motor neurons, the nerve cells that control muscle movements, to deteriorate and die.
“This drug takes the damaged motor system and allows it to function better,” Dr. Shefner explained. “It won’t cure the disease, but it could help people function for a longer period of time and maybe affect survival.”
Dr. Ladha said the drug, which is being administered at 80 sites including Barrow, appears to work well for the breathing muscles. Most ALS patients die of respiratory failure.
“I’m optimistic about the fact that we have more drugs in the pipeline,” Dr. Ladha said. “We know more about the disease than we ever have before, we’re learning about the disease faster than we ever have before, and – thanks to the Ice Bucket Challenge – there is more money for research than there has ever been before. When you put all of those things together, I’m pretty optimistic that we’re going to find something that will help with this disease in the next several years.”