While many people have a surface level knowledge of amyotrophic lateral sclerosis, or ALS, because of the 1920s New York Yankees’ first baseman, Lou Gehrig, or British theoretical physicist Steven Hawking, or the ice bucket challenge that went viral, too few are aware of the complexities surrounding the disease.
For example, most people are likely not aware that every 90 minutes someone in the United States is told they have ALS, or that only 25 percent of patients survive for more than five years after diagnosis. Or, that while physically a patient’s body loses function, cognitively they are aware of what’s happening around them, and that a majority of ALS deaths are ultimately the result of respiratory failure.
These are the current realities. And every day someone (and their loved ones) starts looking for answers.
May is ALS awareness month and with it brings an opportunity to not only raise the visibility of the illness, known to many as Lou Gehrig’s disease, but to actually increase people’s understanding of, or, as the name suggests, provide a true awareness of the frequency, difficulty of diagnosis, treatment advancements and research efforts.
“While symptoms of ALS most often do not develop until after age 50, they can start in younger or older people as well. The first symptoms are typically reported as ’weakness’ in the arms or legs or changes in speaking or swallowing,” said Leo McCluskey, MD, MBE, an associate professor of Neurology and Medical Director of the Penn Comprehensive ALS Center at Pennsylvania Hospital. “As the disease progresses, more muscle groups develop problems. Interestingly, ALS does not affect the senses (sight, smell, taste, hearing, touch) and does not affect the bowels or the bladder.”
The diagnosis of ALS is still considered a diagnosis of exclusion, which means that after performing a history and physical examination, tests, such as an MRI scan or a spinal tap, are often performed to exclude other diagnoses.
“The difficulty in diagnosing ALS can often prove frustrating for patients,” said Lauren Elman, MD, an associate professor of Neurology. “A broad range of diseases can affect nerves and muscles, producing weakness that can look similar to ALS, which makes diagnosing ALS a complex process. The most difficult issue is that there is no single test that can completely confirm or refute the diagnosis.”
Beyond this issue is the harsh reality that there is currently no cure for ALS.
There is only one U.S. Food and Drug Administration-approved disease modifying agent for ALS, riluzole, which slows disease progression, but only minimally. Results from a large clinical trial in the 1990s showed that the drug extended the lives of patients by only three months.
“As a result,” Elman said, “the mainstay of clinical care relies on symptom management with medications, equipment and a strong multidisciplinary team with extensive knowledge of the disease course. We are lucky to have a dedicated team of experts at our Center that provides care to over 250 patients.”
Patients require a team of experienced providers from disciplines, including neurology, pulmonology, nursing, physical and occupational therapy, speech therapy, nutrition and genetic counseling, and often require significant amounts of complex equipment including wheelchairs, non-invasive breathing machines, and surgically placed feeding tubes.
One promising area that could lead to better treatments is genetics.
Over the last 20 years, great strides have been made. Approximately 10 percent of people with ALS have so-called familial disease (meaning that ALS or a related neurodegenerative disease runs in their family and a single inherited gene mutation is responsible for causing the disease). The most common gene mutation is C9ORF72. Some people with ALS without a known family history of disease may also have a mutation in C9ORF72. Currently this gene is a target of much research as a potential therapeutic target.
“Here at Penn, we continue to work toward the ultimate goal of contributing to the development of disease modifying agents,” McCluskey said. “We provide the highest level of care and treatment to our patients who have been diagnosed while continuing to remain an active part of the scientific community and participating in clinical trials through memberships in multiple national and international ALS research consortia.”
Over the last eight years, the Penn Comprehensive ALS Center has participated in 11 high impact clinical trials and currently has two additional ongoing clinical trials, one of which is studying a potential disease modifying agent and the other is studying an agent which may both modify disease and alleviate symptoms.
“In addition, pathologic discoveries first reported at Penn from the laboratory of Dr. John Trojanowski and Dr. Virginia Lee linked the disorders of ALS and frontotemporal degeneration (FTD) pathologically,” Elman said. “As a result, we have been at the forefront of describing the pathologic, radiologic, genetic, and clinical continuum of these diseases.
“We have been able to truly turn this bench discovery into meaningful bedside care through our partnership with the Penn Center for Frontotemporal Degeneration. Penn is unique in having Centers for both of these diseases and our patients benefit from having experts in both areas collaborating on their care.”
The good news is that even today, there are many compounds and treatment strategies in early phase trials for ALS. "It is an exciting time in the world of ALS research as progress is being made at an incredible pace,” McCluskey said.