Actor Courtney B. Vance hopes to promote understanding of ALS

Courtney B. Vance, a Tony and Emmy Award-winning actor, can locate the essence of his mother's character in a single, quiet scene. He was a high school senior at Detroit Country Day School, a private college prep school. His mother, Leslie Vance, was a librarian at a neighborhood branch about a mile from their home. "I said something about her 'little job at the library,'" Vance recalls. "She got quiet, and I recognized immediately that I'd made a mistake." Flashing her expressive eyes, she said, "Courtney, this 'little job' of mine allows you to go to that damn school," and walked away.

That one line summed up his mother perfectly—her strength, discipline, love, sacrifice, and belief in the value of hard work and education. Those values, which both of Vance's parents instilled in him and his older sister, Cecilie, drove him to academic and athletic excellence at Country Day. Artistic excellence followed as an undergraduate student at Harvard, where Vance discovered theater.

His gift for channeling his emotions into characters took him to a master's program at the Yale School of Drama in the mid-1980s. Soon after graduating, he landed roles in movies, on television, and in plays, including the 1987 Broadway debut of August Wilson's Pulitzer Prize-winning Fences and the 1990 film The Hunt for Red October. Vance has had a steady succession of roles ever since, including his portrayal of attorney Johnnie Cochran in the FX series The People v. OJ Simpson: American Crime Story, for which he won the 2016 Emmy Award for Outstanding Lead Actor in a Limited Series or Movie.

Recent years have brought deeper insights into his mother's strength, fortitude, and love. Once again, this new chapter hinged on a quiet moment. It was 2012, and Vance's life seemed full of blessings. In 1997, he married Angela Bassett after meeting the Academy Award-nominated actress at Yale. They'd had twins, a boy and a girl, in 2006, published their joint memoir Friends: A Love Story shortly after that, and were landing good roles. The family had gone to visit Vance's mother in Detroit when their then-6-year-old son made the kind of unfiltered comment children are known for: "Grandma, why are you talking funny?"

A difficult diagnosis

"She was slurring her speech," Vance says. "We'd all heard it, but we thought it was her dentures or didn't want to embarrass her, so nobody said anything." Once the slurring was out in the open, Vance's mother had it checked out. Her doctor and dentist couldn't identify a problem. But acting on an intuition, she saw a neurologist, who finally made the devastating diagnosis: She had amyotrophic lateral sclerosis (ALS).

ALS comprises a group of neurologic diseases that primarily affect neurons controlling voluntary muscle movements, such as those needed for talking, chewing, and walking. As neurons progressively degenerate and die, people with ALS gradually lose the ability to speak, eat, move, and breathe. About 50 percent of people with the disease die within three to five years, usually from not being able to breathe. "About a third of cases start with speech and swallowing difficulties," says Mark Bromberg, MD, PhD, FAAN, professor of neurology and chief of the diagnostic and clinical neurology division at the University of Utah and author with his wife, Diane Banks Bromberg, of Navigating Life with Amyotrophic Lateral Sclerosis. The cause of ALS is not known, and there is no cure.

"ALS is nightmarish," Vance says. "My mother was a very active 78-year-old who had many friends and was involved with many community organizations. To go from that to what you know ALS is—it's an awful transition."

Model of resilience

It wasn't the first awful transition for Vance's mother and their family. In 1990, Vance's father, who'd worked as a foreman and administrator at Chrysler, committed suicide. That experience revealed facets of his mother's strength that Vance didn't know existed. The family counseled her to leave the house she'd shared with her husband, with all of its aching memories. "She said, 'No, baby, this is my house, we paid for it, and I will stay and deal with what I need to deal with. Some things you can't go around. Some things you need to go straight through,'" Vance recalls.

With ALS, however, staying in the Detroit house wasn't an option. Vance and Bassett asked Mama Leslie, as Bassett called her, to come live in their home in California, where there would be space for her to have her own quarters and necessary equipment. "We feel blessed that she allowed us," Vance says. "My father didn't allow anyone to take care of him. My mother was not going down that road. Whatever journey we had to go on, we would go on it together."

"ALS is a family disease," says Terry Heiman-Patterson, MD, professor of neurology and director of the Center for Neurodegenerative Disorders at the Temple University Lewis Katz School of Medicine in Philadelphia. "Everybody living with it eventually needs help on some level, and both psychological support and actual caregiving often comes from the family."

The caregiving burden is high, in part because of the disease's progressive nature. "Just when you get used to a new level of function, it changes again for the worse," Dr. Heiman-Patterson says. "Every day is a new day, and it's a very difficult situation."

Steady decline

At first, Mama Leslie could walk and ride in a car. Then she had difficulty swallowing, eventually requiring a feeding tube. Next came a wheelchair, then a tracheostomy—a surgically made hole through which a tube can enter the windpipe—so that she could use a ventilator to facilitate her breathing and expiration of carbon dioxide.

"If you have good care, you can live on a ventilator for a long time," Dr. Bromberg says. Yet many people with ALS opt not to get a tracheostomy, which requires a high level of care, entails risks of complications such as infection, and can make communication even more difficult. And the disease still progresses, says Dr. Heiman-Patterson. "So even if you have some function when you go on the ventilator, you'll lose that function. People may get to the point where it's no longer what they want, and they can elect to have care withdrawn and the ventilator turned off."

New ways to communicate

For two years, Vance's mother couldn't speak or write, and eventually she couldn't move her body beyond slight motion in her left thumb, which allowed her to ring a bell. To communicate, the family used a dry-erase board with a number and letter system that allowed Vance's mother to identify letters and form words by blinking. "Sometimes it was agonizing," Vance says. "Her mind was always there, and at times I felt frustrated. Then I'd step back and think, 'Why am I the one who's frustrated?' She didn't give up on us, and she didn't give up on life."

The family remained close, with help from professional caregivers and equipment such as an electric hydraulic lift and sling to move Vance's mother from one position to another. Vance would often visit in the afternoon. "We'd get my sister on FaceTime and talk about the day and laugh and joke," Vance says. He'd break for dinner while nurses prepared his mother for bed, then come back later in the evening. "We'd watch a series like The Crown or Game of Thrones," Vance says. "We had a strong rhythm."

Always a Nana

His mother didn't allow her grandchildren to see her at her most vulnerable moments, such as when she was on the lift. "But once she was settled, the kids would come in, and they'd say, 'Hey, Nana,' and go over what they did that day and give her a kiss and say, 'Love you,' and 'Thank you so much,'" Vance says. "She was their nana when she walked them to soccer and taught them to ride a bike, and she was still their nana when they were helping her. She taught them the cycle of life. If you live long enough, you're going to lose somebody, and one day it will be your time."

Ready to go

Despite the limitations and challenges, the family adjusted to each progression, Vance says. "We didn't want to let her go." But his mother let Vance know when the time had come. Leslie Anita Vance died on November 9, 2017, at age 83.

"She taught us what it is to transition and gracefully move to the next phase," Vance says. "At the end there was grace, there were smiles, there was love, there was affection for the nurses. We recognized we were in the presence of greatness." The last word she spelled out on the board: "Pray."

Vance now intends to use his and his mother's experience to heighten awareness of ALS. "During the period my mother was ill, I didn't have time," he says. "But I'm moving toward being available to speak about it. I want to start being a voice for how horrific this illness is and how we need to find a cure for it."

New insights about amyotrophic lateral sclerosis

In 2017, the US Food and Drug Administration (FDA) approved edaravone (Radicava) for amyotrophic lateral sclerosis (ALS) based on a clinical trial that found patients had less functional decline after 24 weeks of the treatment than those taking a placebo.

As the first new ALS drug in a generation, it created understandable excitement among researchers despite its staggering price tag of $146,000 a year. The FDA had approved another drug, riluzole (Rilutek), in 1995, based on a trial that found it increased survival by two to three months, but it did not improve muscle strength and neurologic function, nor did it have an effect in the later stages of ALS.

Now, scientists are working to determine who might benefit most from edaravone—and how their insights can propel the development of new drugs in the pipeline.

Clues in failure

The fact that edaravone at first seemed to fail in clinical trials points to an important consideration, says Orla Hardiman, MD, FRCP, FAAN, professor of neurology at the Trinity College Biomedical Sciences Institute in Dublin, Ireland. "ALS is a spectrum disorder with different subtypes that might respond to different treatments," she says. "We're unlikely to find a drug that works for everybody."

Indeed, Dr. Hardiman says, edaravone won't work for everyone. In fact, in a 24-week trial conducted by researchers in Japan, the drug demonstrated a detectable benefit only in a small subgroup of patients: those in the early stages of ALS with respiratory and motor function, who were still progressing.

Dr. Hardiman and a colleague from the Netherlands estimated in a 2017 comment in The Lancet Neurology that less than 7 percent of patients with ALS would meet the criteria for the study. "The difficulty is that many ALS patients in the United States may want prescriptions for this drug, yet the probability is that it may not benefit the vast majority of them," Dr. Hardiman says.

Finding responders

Despite these limitations, edaravone's approval represents a breakthrough in identifying a responsive subgroup, Dr. Hardiman says. But identifying subgroups depends on discovering biomarkers—substances or traits that are associated with the presence of a disease or symptom and can be measured or tracked, says Catherine Lomen-Hoerth, MD, PhD, professor of clinical neurology and director of the ALS Center at the University of California, San Francisco (UCSF). "A lot of trials are collecting blood and doing experimental analyses to see what biological differences might exist between treatment and control groups with ALS," she says. "Much research is being done on biomarkers, but currently, scientists don't have any they can rely on to track outcomes in studies."

Identifying biomarkers

Having biomarkers could allow researchers and clinicians to predict who might be at risk for ALS, diagnose it in earlier stages, determine how an individual's disease might progress, or assess the effect of medication, says Terry Heiman-Patterson, MD, professor of neurology and director of the Center for Neurodegenerative Disorders at the Temple University Lewis Katz School of Medicine in Philadelphia. One example is neurofilament light (NF-L), a type of protein in neurons that's detectable in blood and, in elevated amounts, is associated with a range of neurologic disorders.

"There may be a rise in NF-L, which we believe is a marker of neurons dying, so you may be able to detect ALS very early and possibly before the manifestation of clinical weakness," says Nicholas Olney, MD, FAAN, ALS research fellow at UCSF's Memory and Aging Center. "That would give you a target to monitor in clinical trials. So if you see a stabilization or fall in NF-L, it would support the idea that your drug is working."

Other potential biomarkers include genetic variations, blood-borne measures of inflammation, and differences in gray or white matter discernible through an MRI technology called phase-sensitive inversion recovery. "We need multiple biomarkers for diagnosis, prognosis, and degeneration," says Dr. Heiman-Patterson. "One biomarker won't serve all purposes."

New therapies

Greater insight into what characterizes ALS and its symptoms could accelerate drug development in a number of areas. Therapies being investigated include, among others, a drug designed to reduce neuroinflammation; an oral drug that blocks the activation of proteins called tyrosine kinases, which play a role in inflammation; and regulatory T cells, which may control ALS-activated immune responses. Other medications include specific anticonvulsants; a drug used for heart arrhythmias; and an antipsychotic drug often used to control the tics of Tourette syndrome. These types of drugs may help control hyperexcited neurons involved in muscle symptoms, says Merit E. Cudkowicz, MD, director of the Massachusetts General Hospital (MGH) Amyotrophic Lateral Sclerosis Clinic and the Neurological Clinical Research Institute at MGH and Harvard Medical School.

"A feature of some of these trials is that researchers are not giving the therapies to everybody, but to those who seem to have the biology they're trying to affect," says Dr. Cudkowicz. "That's a paradigm shift-recognizing that people have different biologies and are at different stages of illness and may be candidates for a particular drug at a particular time."