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Patient is first in Wisconsin to receive recently approved treatment
MADISON, Wis. — For seven generations — as far back as she can track — someone in Michelle Francis’ family has died from a hereditary form of amyotrophic lateral sclerosis, or ALS.
Using genealogy and research from family members, she has documented the names and faces of many of them, 65 in total; a poster she created shows many of their faces to the world.
Though all forms are rare, the disease was made common in the minds of many from the life of Lou Gehrig, who died of a version of the disease, and the “Ice Bucket Challenge” internet sensation in 2014 that raised millions of dollars for ALS research.
Francis and her family have an ultra-rare version of ALS caused by a mutation in the superoxide dismutase 1, or SOD-1, gene that causes the gene to create a toxic protein that forces motor neurons to degenerate, which leads to the muscle weakness for which the disease is known. Patients with all forms of ALS tend to only live a few years after symptoms present.
Francis, who lives in Rockford, Ill., was diagnosed in June 2019 in her late 40s and has been living with the disease for about four years. She first started noticing cramps in her feet and leg pain, but after a year or so the disease progressed to cause the loss of the use of her legs. She now uses a wheelchair but still can transfer herself from the chair.
Now, for people like Francis, a treatment first used in Wisconsin at UW Health is giving her reason to be hopeful.
In July 2020, Biogen, a pharmaceutical company, started a phase 3 clinical trial of a new drug called tofersen. It showed positive early-stage results in slowing the disease’s progression in people with the SOD-1 mutation.
This new, promising, treatment for this inherited form of ALS was brought to Wisconsin by Dr. Collin Kreple, neurologist, UW Health, and assistant professor of neurology, University of Wisconsin School of Medicine and Public Health. He joined UW Health in July 2022 from Washington University in St. Louis, where he was part of the 39-site international phase 3 clinical trial for the drug.
This drug is unique, not only because it is for an inherited form of ALS that impacts about 330 people in the United States, but because it targets a single genetic mutation, he said. There are three FDA-approved treatments for all forms of ALS, but tofersen is the only one approved for the form caused by the SOD-1 mutation.
The drug was approved by the FDA in April 2023 after it showed “nominally significant” reductions in a blood biomarker for the SOD-1 form of ALS called plasma neurofilament light chain.
“It’s exciting because it shows this form of gene-targeted therapy may be an effective way of slowing down this disease,” Kreple said.
Francis, who tried to join the clinical trial since its inception, was not able to participate because she had a slow-progressing form of the condition, and the trial already had enough participants with slow progression, she said. However, while at a conference in 2022 with other people who have ALS, they asked her if she was part of an expanded access program for tofersen. Sometimes called “compassionate use,” expanded access programs can allow a patient with a “serious or immediately life-threatening disease or condition” to gain access to treatment outside of clinical trials when no alternative options are available, according to the FDA.
Starting in late 2022, with Kreple’s assistance, Francis worked to bring the treatment to UW Health and in April 2023, just before the FDA fully approved the drug, she received the first dose.
The drug is administered through a lumbar puncture, which is a shot using a long needle into the bottom of the spine. Some spinal fluid is removed, and then the drug is injected into the spine, replacing the fluid.
Initially, Francis was slightly fearful of the procedure given its description, she said.
“It’s not that bad, if feels like any other shot you would get,” she said. “It’s worth it; I didn’t think I would find a drug in my lifetime.”
The drive to find an effective treatment wasn’t necessarily for herself, but for her family’s future, she said.
“I wanted to do it for my kids,” she said. “At least with this, I can say I was scared, but I did it.”
And now, a few of her extended family members are trying to get on the drug.
Francis receives the treatment once each month, after getting a dose every other week, initially. She rides to Madison with her son, Justin Francis, or daughter, Yvonne Sherrill, or a friend.
Sherrill drove her mom to the first appointment to receive the drug, and despite the travel time each month, it’s worth it to help, she said.
“I’m very hopeful because I want my mom to be OK; I want my mom, I need my mom,” Sherrill said. “I want to bank on the medicine, but not get my hopes up, but I’m hopeful for her, hopeful for me, hopeful for my nieces.”
As the clinical trial data alludes, Francis also has shown improvement in plasma neurofilament light chain, in fact, it has gone down by 50%, Francis said. She has also met people with this form of ALS who take the drug who have reported the progression of their symptoms has slowed or they have even regained some physical function.
Because her condition is so slow-moving compared to most cases of ALS, Francis can’t tell yet if her disease progression has slowed, but she hasn’t noticed it worsen after about six months of treatment.
This is not a surprise to Kreple, who sees Francis’ data regularly and has heard these anecdotes from people in the clinical trial, he said.
What might be most exciting is the opportunity to change the generational damage this disease has caused, Kreple said.
“I think it gives hope for people with this inherited form of ALS,” he said. “It could possibly change that family history of loss, and the idea that you could change this story is really exciting.”