On a quiet farm in Erie County, Pennsylvania, 67-year-old Diane Zaczyk used to think nothing of hefting 50-pound sacks of chicken feed onto her shoulder.
Strong, stubborn and devoted to caring for her flock of chickens, ducks and geese, Diane rarely paused to think about her own health.
For years, the real battle had belonged to her husband, Joel, who endured surgery and treatment for oral cancer.
Diane became his caregiver, whipping up high-protein eggnog by the gallon to help him keep weight on. “Joel’s doctors were always impressed that his weight was really good,” she said with pride.
But not long ago, it was Diane’s strength that began to slip away. She found herself struggling to lift the feed bags she had carried for decades. Then her right foot started to drag. Stairs became harder.
At first, she blamed age or maybe her diabetes. Sometime around Christmas 2023, she could no longer ignore it.
Tests ruled out Lyme disease. Then myasthenia gravis, a neuromuscular disorder. Finally, this past February, came the answer that no one wanted: ALS.
Amyotrophic lateral sclerosis affects the nervous system — specifically, the nerve cells in the brain and spinal cord. The progressive and fatal disease, also commonly known as Lou Gehrig’s disease, causes loss of muscle control, according to the Mayo Clinic.
Experts do not know what causes ALS, but about 10% of cases are inherited, or familial, explained neurologist Sandeep Rana, director of Allegheny Health Network’s ALS Center, who has been treating ALS patients, including Diane Zaczyk, for nearly three decades.
Following Zaczyk’s diagnosis, she underwent genetic testing that revealed she had a very rare, inherited form of ALS — a diagnosis only about 500 people in the U.S. share.
In September, Zaczyk will receive her sixth injection of a monthly genetic treatment approved by the Food and Drug Administration in April 2023 for those with inherited ALS via a mutation of the superoxide dismutase 1, or SOD1, gene.
She is the first patient at AHN to receive it, Rana confirmed. The hospital network is the only provider currently offering the treatment in Western Pennsylvania, according to the Qalsody website.
Qalsody — its generic name is tofersen — is a gene therapy that reduces the levels of the toxic SOD1 protein that is created by the mutated gene. Research has shown that Qalsody reduces a marker of injury to the nerves in the brain, called neurofilament light chain, Rana said.
Neurofilament light chain is a protein that acts as a biomarker for neuronal damage and neurodegeneration. It is released into the cerebrospinal fluid and blood when neurons are injured, per a 2023 study published in the International Journal of Molecular Sciences.
Today, Qalsody is the only FDA-approved therapy that employs antisense oligonucleotide molecules that bind to the SOD1 mRNA, which signals the cell to destroy the mRNA before it can be translated into the harmful protein. The treatment has paved the way for similar approaches targeting other genetic forms of ALS, according to the International Alliance of ALS/MND Associations.
While the Qalsody’s phase 3 clinical trial did not show a statistically significant slowdown in disease progression, it is still considered an ALS treatment breakthrough as it targets the genetic cause of the disease, according to a 2023 article by Columbia University Irving Medical Center.
When the gene that is responsible for Zaczyk’s form of ALS mutates, it doesn’t just stop working — it actually gains a harmful new function. The mutation makes the gene produce an abnormal protein, and that protein damages the body, Rana explained.
If doctors can “quiet” or turn down the activity of the gene via monthly lumbar injections of Qalsody, like Zaczyk receives, the gene stops producing that toxic protein, which can help prevent further damage, Rana said.
Another AHN patient was set to receive the treatment, but died from ALS complications before it could begin, Rana said. “By the time she reached us, the disease had already progressed quite a bit.”
Early diagnosis of ALS is essential, especially in the case of those patients like Zaczyk who have the SOD1 mutation, Rana said.
While the treatment, which is injected directly into the spinal column during a hospital visit, cannot cure or reverse the disease, researchers believe more testing will reveal that it has the ability to halt additional damage and slow down the progression of symptoms that have already begun, Rana said. “We wanted to get the word out that there is this potential treatment available.”
So the Zaczyks make the trek to Pittsburgh from their Union City home — about 5 hours round trip — every month so she can receive the injection and get checked over by her medical team.
In August, she suffered a bit of a setback, after a small spill at home resulted in a broken leg. She missed her August injection but expressed optimism that the lull in treatment may be useful in upcoming diagnostic testing. The results could reveal how well the treatment is working and whether it is slowing down the production of the toxic protein from her mutated gene, she said.
She said the injections — so far — have few side effects aside from some muscle stiffness the next day. But she admitted that might just be from the long car ride.
“I started rather late. I was pretty much already in the wheelchair. If someone was able to find out they had this much earlier, their whole physical progress might be affected, might be totally different,” Zaczyk said.
That’s why Zaczyk wanted to share her story: to raise awareness and to urge others to start talking to their doctor right away if they’re noticing sudden weakness and other potential ALS symptoms. And to urge them to insist on genetic testing to see if they too might be a candidate for the treatment.
Early signs of ALS
ALS “starts with a weakness,” Rana said. “Usually, it’s painless weakness. It could be in the hand, it could be in the leg. It could also sometimes start at the tongue,” causing slurred speech or difficulty swallowing.
From there, ALS spreads to other parts of the body, and “it’s relentlessly progressive. Most classic ALS patients, usually survival is about three to five years after the onset of symptoms. So it’s a pretty rapidly evolving disease.”
Often, patients are bedridden within two to five years from onset, he said.
There are no significant differences in how an inherited ALS subtype like Zaczyk’s presents compared to the more common ALS manifestation, Rana said.
“You cannot tell them apart. They look the same.” Inherited ALS can only be revealed via genetic testing, which, Rana said, is becoming an essential tool for patients. As more treatments are approved, some will likely prove more effective for specific forms of the disease.
Once a patient is diagnosed with this inherited form of ALS, their family members may also choose to undergo genetic testing to see if they also share the gene.
Zaczyk said she has shared her diagnosis with relatives across Ohio, Pennsylvania and New York. Some have shown interest in genetic testing, while others prefer not to know, wanting to avoid the worry that can come with the results. Still, they understand the importance of seeing a doctor if they ever develop muscle weakness like she experienced at the onset of her illness, she said.
While ALS remains incurable, therapies like this give patients hope, slow their progression of symptoms and ultimately give them more time with their loved ones, Rana said.
“Our hope is that we can slow down the disease, give them more time, and maybe even halt it for longer periods of time,” he said. Keeping patients independent in their “acts of daily living improves the quality of life.”
