UHealth’s Qalsody Clinic Provides Cutting-Edge Care for ALS Patients
Summary
- The University of Miami’s Qalsody Clinic is one of six specialty clinics at the ALS Center tailored to meet the needs of patients with Lou Gehrig’s disease.
- The Qalsody Clinic has become one of the nation’s top clinics for patients with SOD1 ALS.
- Tofersen is helping some ALS patients regain abilities that they once assumed were lost forever.
Amanda Sifford is amazed she’s still alive. Like many in her family, she has a genetic form of amyotrophic lateral sclerosis (ALS), also called Lou Gehrig’s disease, a progressive and ultimately fatal neurological condition.
Sifford keeps treasured photos of more than a dozen loved ones who died of ALS. Losing her father to the disease was the most painful. They also carried the rare SOD1 mutation that almost ended her life. Around 2% of ALS patients are SOD1 positive.
ALS gradually destroys motor neurons, leading to muscle weakness, paralysis and, eventually, respiratory failure. By 2023, Sifford’s lung function had declined so severely that even basic daily tasks became exhausting.
“I could barely walk from my front door to the car,” said Sifford, a public-school psychologist from Cape Coral, Fla. “Just bending over (to get into the car) would compress my diaphragm. I’d have to sit there for three or four minutes just to catch my breath enough to drive.”
Amanda was initially a participant in a long-term observational study at the University of Miami Miller School of Medicine’s world-class ALS research program.
Amanda may have only had a few months to live when, in April 2023, the U.S. Food and Drug Administration approved toferson (brand name Qalsody), a breakthrough drug treatment for SOD1 ALS. Tofersen works by reducing the overall amount of SOD1 protein, including its toxic form, that drives neurodegeneration in patients with her form of genetic ALS. For Sifford and others, it’s been more than a treatment. It is a second chance at life.
After about six months of treatment, Sifford noticed that her breathing had become easier.
“We never expected this kind of stabilization, let alone improvement,” said Nathan Carberry, M.D., a neurologist, assistant professor of clinical neurology at the Miller School and founding director of the Qalsody Clinic at UHealth — University of Miami Health System. “It’s giving patients back function and, in many cases, time.”
Establishing the Qalsody Clinic
The Qalsody Clinic is one of six specialty clinics at the University of Miami ALS Center tailored to meet the needs of patients with Lou Gehrig’s disease. The center, the largest of its kind in Florida, provides care for about 400 patients and seamlessly integrates clinical care and research.
UHealth became one of the first institutions nationwide to offer tofersen. The Qalsody Clinic, part of the Department of Neurology’s Division of Neuromuscular Disorders, has quickly become one of the nation’s top clinics for patients with SOD1 ALS. The ALS Center, a designated Center of Excellence by the ALS Association, has a longtime reputation for comprehensive care and research. Patients travel from across the United States and even from abroad to receive specialized treatment at the clinic.
Until now, drugs developed for ALS have only offered the hope of slowing disease progression. Tofersen is different in that patients like Sifford are regaining abilities that they once assumed were lost forever. One of Sifford’s favorite pastimes is dancing and, for years, she simply couldn’t do it. Recently, she went dancing with friends in Key West. Tofersen gave that back to her.
“We’re seeing something we haven’t seen before in ALS,” said renowned ALS expert Michael Benatar, M.D., Ph.D., the Walter Bradly Chair in ALS Research, chief of the Neuromuscular Division, professor of neurology at the Miller School and executive director of The ALS Center. “For patients with SOD1 mutations, this is a potentially transformative therapy. And timing matters. We believe that it is imperative to start treatment as early as possible in order to maximize benefits.”
While tofersen has been quite effective at slowing SOD1 ALS, there are significant risks. The drug can trigger an inflammatory response and may result in serious side effects, such as spinal cord inflammation (myelitis), dizziness and refractory headaches with elevated intracranial pressure.
When Sifford experienced myelitis and was hospitalized, Dr. Benatar and Dr. Carberry used the knowledge gleaned from using tofersen in research studies and in the clinic to treat the inflammation, which allowed her to recover.
“Myelitis causes severe weakness and someone who’s not familiar with that side effect might think it’s ALS progression,” said Dr. Carberry. “It is essential to differentiate disease progression from treatment-related complications, notably inflammation. We pay close attention to these kinds of nuances. By innovating better ways to manage the side effects, we can keep patients on this beneficial medication for longer.”
From Research to Reality
The research team led by Dr. Benatar and Joanne Wuu, Sc.M., research associate professor of neurology at the Miller School and the associate director of research at the ALS Center, has spent years studying how a protein called neurofilament light chain (NfL) might be used as a biomarker to aid therapy development.
“The progress we’re witnessing today is the result of decades of research by many scientists around the world,” said Dr. Benatar. “Biomarkers like NfL have emerged, not only as important research tools, but also as a helpful prognostic marker and a mechanism to monitor treatment response to tofersen in the clinic.”
In 2018, Dr. Benatar and Wuu published seminal data showing that, for people at genetic risk for developing a form of SOD1 ALS, the concentration of NfL in the blood goes up before symptom onset. That finding and their body of work has made an indelible impact in the field and ALS clinical trials. The FDA’s decision to grant accelerated approval to tofersen was based, at least in part, on the impact of the drug in lowering NfL.
The Benatar-Wuu Research Group has been studying SOD1 and other forms of ALS for nearly two decades. In 2007, Dr. Benatar initiated the Pre-Symptomatic Familial ALS (Pre-fALS) study, which follows people with SOD1 as well as other mutations who do not yet show any signs of the disease, to better understand when and how the disease begins and if it might be possible to prevent ALS.
Sifford joined Pre-fALS in 2011 because more than a dozen people in her family had died from SOD1 ALS. While in the study, she began developing symptoms of ALS, albeit very gradually. But by November 2023, the disease had progressed to the point that it compromised her breathing. At the time, her slow vital capacity, a measure of lung function, was around 34%. Since starting tofersen, that number has increased to 59%.
“I had tears when they came back in the room with the results,” Sifford said.
Making an Effective Drug Better
After successfully treating Sifford’s brief bout with myelitis, Drs. Carberry and Benatar continue to give Sifford intrathecal steroids with each tofersen infusion, as well as an additional maintenance medication, to mitigate the risk of complication recurrence.
With her side effects stabilized, Sifford is seeing ongoing improvements. The disease had made walking difficult, and she couldn’t step onto a curb without assistance. With the infusions, she regained that capability.
International Reach
SOD1 ALS can cause disease in patients when they are quite young. Andres Dorigoni, who lives in Guatemala and was referred to UM by his caregivers, travels to Miami each month for his tofersen infusions. He is only 33.
“Living with ALS has been a great life challenge,” said Dorigoni. “I am the father of a 4-month-old baby, and my greatest desire is to always be there for him. Having lost my mother and sisters to this same disease makes me aware of what it means and how it affects every aspect of my life.”
He has only recently started the treatment, provided by Biogen. The drug has stabilized his strength and he shows no evidence of further progression.
“These changes have allowed me to feel stronger and look forward to a better quality of life, which also gives me confidence and encouragement to continue facing this condition,” Dorigoni said.
Dr. Carberry remains optimistic about his continued disease stabilization.
While the ALS research community hoped that the effects of tofersen would be dramatic, Dr. Benatar and team members said that it wasn’t initially clear how the drug would impact patients.
“What’s remarkable is that we are seeing patients’ strength improve, a first for ALS,” he said.
All patients in the Qalsody Clinic have normalized NfL levels after receiving the drug, said Dr. Carberry. One study by researchers at Washington University in St. Louis showed that the drug increased arm, leg and diaphragm strength in a small group of patients.
Can Tofersen Prevent SOD1 ALS?
The research team’s work is also strongly geared toward prevention. In partnership with Biogen, Dr. Benatar designed and is spearheading the well-known ATLAS clinical trial to determine whether tofersen, if given early enough, can prevent SOD1 carriers from developing clinical manifestations of ALS.
“Now, we’re focused on early treatment, even before patients have symptoms,” said Dr. Carberry, who is also an integral member of the Benatar-Wuu research team. “The aspirational goal for ATLAS is to delay or even prevent the onset of ALS symptoms.”
Depending on the results of the ATLAS trial, the Qalsody Clinic might have an added mission: To prevent ALS in presymptomatic SOD1 mutation carriers. Until then, the clinic remains a lifeline for SOD1 ALS patients, even the ones receiving care elsewhere.
Sifford is making sure her peers know about the clinic and the care she receives there. She comments regularly on ALS forums and elsewhere, often praising her UM caregivers and research team, who have provided extensive care and support for the past 15 years.
“The medical team at the University of Miami is topnotch,” she wrote in a recent social media post. “I am so fortunate to be under their care.”
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Tags: ALS, ALS Center, amyotrophic lateral sclerosis, center of excellence, Dr. Michael Benatar, Dr. Nathan Carberry, Newsroom, SOD1 genetic mutation