The impact of genetic ALS

For many patients and caregivers with neurological diseases, receiving a diagnosis often triggers a complex series of emotions.  And while it’s an answer that helps provide clarity, it’s not always the answer one wants to hear.  This reality is especially evident when genetics are involved, as the decision to get tested comes with potentially life-altering outcomes – not just for yourself, but for your entire family. 

Jeremy S. exemplifies this challenge. With the passing of his uncle and the gradual confirmation that a number of his family members carry C9orf72 mutations, which can lead to either amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD), Jeremy began looking into educational information around genetic ALS. His decision to get tested was deeply personal and, despite the results, he has shown great resilience and says that his biggest fear is failing to seize the day.

Jeremy’s Story with ALS

In 2015 Jeremy received news that his uncle had passed away from ALS. It was the first time a person in his family had been diagnosed with this disease, and while Jeremy was understandably bereaved, he assumed it was an isolated incident. Unbeknownst to Jeremy, however, his uncle had suffered from a form of ALS caused by a genetic C9orf72 expansion mutation – meaning that both he and his entire family would be at risk of inheriting the gene causing the disease.

Fast forward to 2019 and Jeremy received a distressing phone call. It was his cousin Jon, who explained that both Jon and Jon’s older brother Seth had been recently diagnosed with ALS caused by the C9orf72 expansion. Immediately, Jeremy understood that he was at risk and knew that he needed to get both himself and his mother tested. After receiving the results, Jeremy learned an unfortunate and devastating truth: they would become the fourth and fifth members of his family to test positive for the gene responsible for 20-30 percent of genetic ALS cases worldwide1.

Jeremy S. (middle) with cousins Jon (left) and Seth (right)

“After understanding the implications that this genetic defect would have on my entire family, I was simply devastated. Nothing can prepare you for something like this,” Jeremy explains. “One of the most difficult things to deal with is the uncertainty. While I’ve been told I will definitely develop one of the diseases associated with the mutation, nobody can give me a timeframe. Even within my own family, you can see the variability in the [age of] onset of the disease.”

The collective trauma that Jeremy and his family experienced following his results was unfathomable. Not only was this information difficult to comprehend, but it sent a ripple effect through his entire family – as other close relatives realized they may now be at higher risk. For Jeremy and his family, the questions immediately became: “Who else should get tested?,” “Are there any treatment options?” and, perhaps most importantly, “What do we do now?”

“I took some time away from my job to wrestle with my newfound reality and to contemplate what I wanted the rest of my life to look like,” Jeremy states. “It’s hard to plan for the future when things are so uncertain. I also think a lot more about the legacy I’m going to leave when I’m no longer here.”

As Jeremy contemplated his next steps, he committed to do whatever he could to ensure that future families would never again have to experience the same hardship that his family continues to endure. He joined clinical studies, sought out resources and worked to advocate for broader education surrounding genetic ALS and its impact on families everywhere. This brought him to Biogen.

Biogen’s Story with ALS

For nearly a decade, Biogen has remained unwavering in its commitment to furthering ALS research in an effort to bring therapies to people living with this rapidly progressing neurological condition. Starting in 2012 the company began a discovery and development program, carrying out a Phase 3 clinical trial called EMPOWER for broad ALS. Unfortunately, the trial failed to meet its primary endpoint and no efficacy was seen in individual components of function or survival – though much valuable information on the disease course in individual patients was collected.

It was this data, and the insights they provided on the individual level, that shifted Biogen’s focus to genetic ALS, with the goal of bringing a potential therapy to patients in need.

ALS is a rare, fatal neurodegenerative disease characterized by motor neuron loss in the brain and spinal cord. At present, about 10 percent of ALS cases are caused by a known genetic mutation that can be passed from one generation to another, while a staggering 90 percent have no known cause. Nevertheless, scientists believe it is likely that additional genetic mutations have yet to be identified – underscoring the importance of Biogen’s continued work in understanding ALS genetics.

“Our understanding of ALS has really exploded over the last 10 years,” explains Chris Henderson, Ph.D., Senior Vice President and Head of Research at Biogen. “We now understand the genetics of many human cases, which has provided us with the ability to directly target the causal genes in those patients. These genetics have allowed scientists to create animal models in the laboratory that quite faithfully represent several of the degenerative processes going on in ALS patients. By studying these models, as well as human tissue samples, researchers around the world have brought to light new biologies that we now believe to be involved in all forms of the disease. And each new biology is a potential target for a therapeutic, even in patients that have ALS with no known genetic cause.”

Chris Henderson, Ph.D.
Senior Vice President and Head of Research at Biogen

By applying emerging learnings about appropriate modalities and sensitive endpoints, Biogen began pursuing an antisense oligonucleotide (ASO) strategy that selectively targets some known genetic drivers of ALS including superoxide dismutase 1 (SOD1) mutation and C9ORF72 expansion – with the goal of potentially treating the same genetic mutation that has impacted families like Jeremy’s. The company is also working on a program targeting ataxin-2 (ATXN2), a gene that may be more broadly involved in ALS.

“We’ve witnessed incredible acceleration over the last years in terms of turning science into potential drugs for ALS,” Chris mentions. “But the scientific community could not have done this alone. I’ve been so impressed with the maturity and generosity of this group of patients and their willingness to support the development of potential therapeutics that in some cases may only benefit future generations.”

It’s a sentiment echoed by Jeremy who, when asked about his personal involvement in advocacy groups for the advancement of research into genetic ALS, stated: “I’ve found a really inspiring group of young asymptomatic gene carriers and together, with the support of I AM ALS, we've started the first advocacy group focused on genetic ALS. We understand how important patient involvement is from a research perspective and are constantly looking for ways to accelerate progress and, hopefully, contribute to finding a cure.”

With a mixture of perseverance, determination and an incredible spirit of collaboration between both patients like Jeremy and researchers around the world, Biogen is hopeful that the future of treating ALS is brighter than ever.


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