Peter Frampton found new purpose after inclusion body myositis diagnosis

Ten years ago, at age 60, Peter Frampton thought, "I'm getting old." The singer and guitarist—whose double album Frampton Comes Alive!, featuring classics like "Show Me the Way" and "Baby, I Love Your Way," topped the charts for 10 weeks in 1976—was in Big Sur, CA, with his son, Julian. "It was a father-son rustic weekend," Frampton recalls. "We took our guitars, we jammed, I wrote a song, and we went hiking in this beautiful area." At a rise in the trail, Julian was "up the hill in a flash," Frampton says. "I was far behind. When I got to the top, I looked at him and said, 'You know, Julian, I'm finding this more difficult than usual.'"

Frampton now pinpoints that hilltop moment as the first hint that something was wrong. At the time, the United Kingdom native chalked up his fatigue to wear and tear from a decades-long career that has encompassed playing in bands the Herd and Humble Pie; collaborating with fellow music legends such as George Harrison, Jerry Lee Lewis, Ringo Starr, and boyhood chum David Bowie; touring with Cheap Trick, Gregg Allman, Lynyrd Skynyrd, Stevie Nicks, and the Steve Miller Band; and winning the Grammy Award for Best Instrumental Album, for Fingerprints, in 2006.

But foreboding signs continued, including when Frampton found it difficult to run while tossing a Frisbee backstage a few years after the Big Sur hike. For two years he continued dismissing a sense that things were not quite right. Then, in 2015 he fell on stage twice in three weeks. "I got up and we all laughed, but it was humiliating," he says.

And sobering enough that he went for a checkup in Nashville, where he'd recently reestablished residency after a long stint in Ohio. Immediately his primary care doctor noticed that Frampton had lost 10 pounds since they'd last met. "He thought we should look into it," Frampton says. "Thank goodness he did."

Frampton was referred to a neurologist, who instructed the musician during the exam to make a fist and keep it tight. Despite Frampton's efforts, the doctor could easily pry the fingers back from his palm. The doctor also asked Frampton to jump 10 times on each leg. On his right leg, he had no problem; on his left, he could manage only four jumps.

After laboratory testing, the neurologist sat Frampton down and told him he'd initially thought Frampton might have amyotrophic lateral sclerosis (ALS). "But you don't have ALS," the doctor said. "You have IBM [inclusion body myositis]." Like ALS, IBM is a progressive neuromuscular disorder, but unlike ALS, it's not fatal. Further tests, including a muscle biopsy, confirmed the diagnosis.

"I've had ups and downs throughout my life," Frampton says. He was arrested for driving while intoxicated in younger days, his career cratered after superstardom but was later resurrected, and he was in a serious car crash in the late 1970s. "I knock the dust off and get myself back up," says Frampton, who no longer drinks. "I'm very pragmatic about this disease and am always positive. I have to be. IBM isn't life-ending, it's life-altering.

A Rare and Disabling Disorder

Like ALS, IBM causes muscles to weaken and atrophy. But the two diseases differ significantly beyond IBM's survivability. Inclusion body myositis progresses more slowly and typically affects muscles in an asymmetric pattern—the reason Frampton's neurologist tested whether leg strength and balance were greater on one side than the other. Frampton was 10 pounds lighter in part because he'd lost muscle.

Muscles usually affected by IBM include the quadriceps, which help lock the knee and provide power while walking up steps. Lack of strength in these muscles can trigger falls, which is often why people go see a doctor. IBM also affects finger flexors, the forearm muscles that enable finger movement and dexterity. "That's not good for a guitarist," says Yadollah Harati, MD, FAAN, professor of neurology and chief of the neuromuscular section at Baylor College of Medicine in Houston. "Movements that involve grabbing objects—like turning a car key, using a screwdriver, holding utensils, or turning a doorknob—often become more difficult."

A minority (about one-third) of people with IBM eventually have trouble swallowing, although Frampton hasn't experienced this symptom. Other than a surgical procedure to treat swallowing problems, IBM has no available treatment or cure. "Ultimately, it becomes debilitating," Dr. Harati says.

The condition is considered rare, affecting an estimated 30,000 Americans. "I think it's much more common than what we identify," Dr. Harati says. The disease typically develops after age 50, most often in men (who are two to three times more likely to get IBM than women), so symptoms may be attributed to aging or mistaken for arthritis, ALS, or other muscle disorders. Getting an accurate diagnosis often takes five to eight years. "People think becoming significantly weaker with age is normal," Frampton says. "It's not."

Neurologists sometimes refer to IBM more specifically as sporadic inclusion body myositis, or sIBM, to distinguish it from an even rarer variant called familial inclusion body myositis (fIBM), which—unlike sIBM—runs in families. (Similar-sounding inclusion body myopathies are an entirely distinct set of genetic diseases.) Outside of research circles, "IBM" is often synonymous with sIBM.

IBM's cause is unclear and continues to be debated. "Myositis" refers to inflammation of muscle, and "inclusion body" refers to abnormal protein clumps within empty spaces called vacuoles that are visible in biopsied muscle cells. Inflammation suggests IBM is an autoimmune disorder, in which the immune system attacks healthy tissue. Yet drugs usually prescribed for autoimmune disorders, such as corticosteroids and immunosuppressants, tend to have little or no effect against IBM. There may be a link between sIBM and acquired dysfunction of the mitochondria, the energy-producing component of cells, says Bruce H. Cohen, MD, FAAN, director of the brain, muscle, and mitochondrial research program at the Children's Hospital Medical Center of Akron, OH. The most current research suggests the mitochondrial problem may be the cause of sIBM, he says, but no therapies approved by the US Food and Drug Administration are available for mitochondrial disease.

After his diagnosis, Frampton went to see Lisa Christopher-Stine, MD, director of the Johns Hopkins Myositis Center in Baltimore. With rock-star stereotypes in mind, Dr. Christopher-Stine wondered if Frampton would be a demanding, entitled patient. "He was the opposite," she says. "He was disarming, genuine, charming, and a lovely human being from the first moment. It took about a minute to feel like I was speaking to an old friend."

Clinically, her first impression was that Frampton was a typical IBM patient—male and older than 50. But then she discovered something remarkable: Frampton could still play guitar at a rock-god level. "I assumed everybody's finger flexors got weak," she says. "But his ability to work them was preserved."

Music and exercise help

Frampton has had some weakness in his hands, but his playing has not been affected. "I can't lift things over my head and wouldn't be able to put stuff in the overhead compartment on airplanes," he says, five years after that first exam. "But on guitar, I'm still at the top of my game."

This revelation shifted Dr. Christopher-Stine's thinking. "He brought to my attention how little we use our fingers the way he does," she says. "We don't have data to project where he will be in five more years, and one size doesn't fit all. However, he's one of my slowest-progressing IBM patients overall. Maybe if you use your fingers that often, it delays the inevitable." If true, this could have implications for maintaining quality-of-life skills such as buttoning a shirt or using the toilet unassisted. She has started suggesting to patients that they take up guitar or piano.

Activity in general helps maintain function, Frampton believes. He exercises six days a week-getting his heart rate up on the treadmill or a stationary bike and doing lunges to prevent falls—and had a trainer with him when he performed on the road. Since the COVID-19 pandemic, he logs on to Zoom for trainer sessions, continuing to maintain his six-days-a-week schedule and making the most of at-home equipment such as elastic bands and free weights. "My stairs are my stair climber!" he says.

Neurologists recognize the promise of exercise but are reluctant to give a blanket endorsement to any particular regimen. "The best data suggest that patients who are more functional and have better outcomes after having the disease a long time are more likely to have exercised," says Conrad C. Weihl, MD, PhD, professor of neurology at Washington University School of Medicine in St. Louis. Although there's a chicken-and-egg question about whether exercise allows function or the other way around, "I tell all patients they should exercise," Dr. Weihl says.

But he's mindful of another finding: "Patients given an exercise program by a physical therapist don't do as well as those who just do what they enjoy," he says. "You might not go to a gym, but maybe you'll play pickleball or do tai chi." What's important is doing an activity you'll stick with—and being safe while exercising. "You don't want people to fall or hurt themselves," Dr. Weihl says.

Overexertion is another concern, says Dr. Harati. "The goal is to keep existing muscle alive and working with consistent, moderate activity," he says. With strenuous exercise, patients risk breaking down muscle further or triggering an immune response. "Going to the gym and lifting heavy weights will not beat the disease," Dr. Harati says. "It could even be detrimental."

Rockin' for research

With the clock ticking on a career-ending disease, Frampton has pushed to perform as much as he can while he's still able. "I do not want to be that guy up on stage who cannot play what he wants to play," he says. "I only want to do it if I can enjoy myself, and that means I've got an audience that's enjoying it too."

After falling again while on vacation in Hawaii in early 2019, Frampton decided to stage farewell concerts, kicking off with a 51-date tour of the United States in summer and fall 2019. He also went public with his diagnosis in an interview on CBS This Morning in February 2019. "In every interview for the tour after that, IBM would be mentioned," Frampton says. "Everyone was aware."

He established the Peter Frampton Myositis Research Fund at Johns Hopkins to raise money for research. One dollar from every ticket for the US tour, along with proceeds from T-shirt sales, went to the fund. Shriners Hospitals for Children contributed half of its fundraising sales from one of his records. In addition, some famous artists gave, according to Dr. Christopher-Stine. "And certain promoters handed me $5,000 checks out of the blue," Frampton says. Donations from the tour totaled more than $275,000, Dr. Christopher-Stine says.

Frampton now sees advocacy for IBM as his new vocation. "I will always be raising awareness and money for my research fund," he says. The money will help pay for clinical trials, such as the one Frampton enrolled in to test the effect of the diabetes drug pioglitazone on IBM. The trial was scheduled to start for him last spring just as the COVID-19 pandemic shut the country down. "Because of my diagnosis, I have to be very careful," Frampton says. "I couldn't travel to Johns Hopkins to start the trial, but my doctors have made the drug available to me without traveling."

He recognizes that pioglitazone may not help. "But if I can't be cured, I will have done my little part to help scientists come up with the right drug and make sure future generations won't have to deal with this disease," Frampton says. Before the pandemic, he had intended to speak at medical conferences and possibly meet others with IBM, but those plans are now on hold.

A hoped-for European farewell tour also has been scrubbed, with no plans yet to reschedule. During the pandemic, Frampton has been keeping busy at home with recording projects for charities, such as "Ringo's Big Birthday Show," an online benefit that celebrated the former Beatle's 80th birthday on July 7. A tribute video Frampton posted on YouTube features photos of the two together over the years—they met in 1969—along with footage of Frampton playing Starr's "It Don't Come Easy" on three different guitars.

On tour before the pandemic, Frampton didn't tell fans he was wearing a leg brace under his jeans to support his knee and refrained from mentioning IBM until the end of a performance. "Then I'd say, 'You know I have health issues, but all I can feel is loving warmth coming from you as if you're trying to hold me up,'" he says. "It was a phenomenal feeling."

"Having a figurehead for this disease is important," Dr. Weihl says. "Parkinson's has Michael J. Fox; spinal cord injury had Christopher Reeve." Frampton helps people identify with a larger community and explain their disease to friends, says Dr. Weihl. His advocacy also can aid researchers seeking participants for clinical trials. "We can only gain knowledge from the patients we know about," Dr. Weihl says. "That's why the awareness that Peter Frampton is bringing right now is so important."

At his 2019 concerts, Frampton invited anyone in the audience who had IBM to come backstage for a meet-and-greet. "One man told me, 'I'd been to so many doctors, and nobody had a clue what was wrong with me. Then one morning I turn on CBS, and there you are talking about this disease,'" Frampton relates. "The man said he had checked off his symptoms as I described them, then turned to his wife and said, 'Hon, Frampton just diagnosed me.'"

Frampton's memoir Do You Feel Like I Do? (Hachette) will be available in bookstores toward the end of October. Between October 2018 and June 2019, he and his band recorded three albums in his Nashville studio. All Blues (UMe), released last year, was No. 1 on the Billboard blues albums chart for 15 weeks. He recorded a second blues collection and is finishing production on an all-instrumental album. "They're all cover songs because I didn't know how long I had left to play and didn't think I had time to write new stuff," says Frampton, who's now at work on a solo album of new material. "I have no plans for stopping," he says.

While he's always been drawn to the blues, Frampton hadn't considered the poignancy of a song by St. Louis Jimmy Oden called "Going Down Slow" until he recorded it for All Blues. As Frampton sang, he could sense the rest of the band quieting even as they all propelled the rollicking tune forward. "I have had my fun if I don't get well no more/You know my health is now fading and I'm going down slow," Frampton sang.

"It was as if I could hear their thoughts and mine," he says. "I couldn't help but ponder at that point why we were recording so much so quickly. I had a little moment with that one."

The state of IBM research

No effective treatment for inclusion body myositis (IBM), a neurologic disorder that rock star Peter Frampton was diagnosed with in 2015, has been found so far, and several drugs have proved disappointing in clinical trials. "But this is an exciting period in IBM research, and Peter Frampton is increasing awareness just at a time when I believe therapies will emerge," says Conrad C. Weihl, MD, PhD, professor of neurology at Washington University School of Medicine in St. Louis.

In one area of research, neurologists are investigating the role of cytotoxic T cells. Sometimes called killer cells, cytotoxic T cells are responsible for attacking and destroying other cells in the body. Usually they target invaders such as infectious agents, but in autoimmune diseases, cytotoxic T cells can attack healthy tissue.

"One potential approach to treating IBM might be targeting the specific population of T cells involved," says Steven A. Greenberg, MD, professor of neurology at Harvard Medical School and associate neurologist at Brigham and Women's Hospital in Boston. As cytotoxic T cells become more evolved and differentiated over time, they also become more potent. "Targeting highly differentiated T cells that have been around in the body for years honing their attacks, getting stronger, and dividing more might be a way to treat IBM," Dr. Greenberg says. He chairs a medical advisory board for a company that is preparing to begin clinical trials of a drug that binds to select cytotoxic T cells and destroys them without depleting helpful T cells.

Other trials are continuing or have been proposed for drugs that have failed to meet target goals in previous research. These include arimoclomol, a drug that prevents the abnormal clumping or folding of proteins that is thought to cause muscle damage in IBM, and rapamycin, an immunosuppressant given to kidney transplant patients. The drug bimagrumab, which binds to receptors along a molecular pathway shown to have potential muscle-sparing activity, generated early excitement but performed poorly in clinical trials. "Either the drug is ineffective or we don't have a good grasp of the right end points to study," says Lisa Christopher-Stine, MD, associate professor of medicine and neurology at Johns Hopkins Medicine and director of the Johns Hopkins Myositis Center in Baltimore.

Before the COVID-19 pandemic, Frampton had enrolled in a trial of pioglitazone, a diabetes medication that increases production of an enzyme linked to improved mitochondrial function, which contributes to energy in cells and that is impaired in people with IBM. "This is a pilot study to see if we can detect beneficial signals in blood tests or muscle biopsies," says Dr. Christopher-Stine. "The answer might not be this drug but another that's developed based on successfully targeted pathways we see—such as increasing PGC-1, a key regulator of energy metabolism that may protect skeletal muscle from atrophy."

Pioglitazone is one of many drugs that increase PGC-1, says Bruce H. Cohen, MD, FAAN, director of the brain, muscle, and mitochondrial research program at the Children's Hospital Medical Center of Akron, OH. "Exercise is another potent way to increase PGC-1 quickly, but you need to keep exercising," he adds. Unlocking clues in IBM may unlock clues for treating diabetes, Parkinson's disease, some dementias, and even cancer, Dr. Cohen says.

IBM's rarity can challenge researchers recruiting patients for clinical trials. "We need to know more about how patients progress and what they consider meaningful," Dr. Weihl says. To find current trials, search "inclusion body myositis" at clinicaltrials.gov.