2026 Breakthrough Prize Recognizes the Shared Genetic Cause of ALS and FTD

Today (April 18), the Breakthrough Prize Foundation announced the recipients of the 2026 Breakthrough Prizes for Life Sciences, Mathematics, and Fundamental Physics. These awards celebrate the achievements of scientists and inspire the next generation of researchers.

This year, one of the Breakthrough Prizes in Life Sciences has been awarded to Rosa Rademakers, a neurogeneticist at the University of Antwerp, and Bryan Traynor, a neurologist at the National Institutes of Health. They are recognized for the identification of the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Their work has significantly advanced understanding of the genetic basis of these diseases.

“There are so many fantastic things going on in science, and then to have our specific research be selected, I think is amazing…We can only do these studies because of all the collaborators and all the patients who contributed their samples,” said Rademakers.

A Tale of Two Diseases: Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Among neurodegenerative disorders, ALS and FTD have long been regarded as separate entities, yet they have drawn particular attention because of their unexpected overlap. ALS is a disorder that primarily targets motor neurons. As these cells degenerate, motor control declines, leading to muscle weakness, atrophy, and, in advanced stages, the loss of voluntary movement. In contrast, FTD most often affects individuals in their forties and fifties and involves degeneration of the frontal and temporal lobes, progressively impairing personality, behavior, language, and memory.

Despite these differences, clinicians began to observe a striking connection between the two conditions. Historically, both have cases that run in families: One sibling might develop ALS; another develops FTD, or worse—develops both. But what was this seemingly shared genetic cause? This overlap prompted Rademakers and Traynor to investigate further through independent yet simultaneous efforts.

The Hunt for the Genetic Cause of ALS and FTD

Using Population-Based Studies for ALS

For Traynor, the question began at the clinical level. As a neurologist, he treats patients with very different symptom profiles. Despite these differences, a common underlying proteinopathy appeared in both conditions.¹ The key question was: Why?

Looking more closely at patients with ALS, Traynor began to notice changes in executive function “that you would expect in frontotemporal dementia.” What truly sparked his interest was when he studied an Italian family with ALS and profiled them using exome sequencing. “And lo and behold, the gene that we found in that Italian family, the mutation was in a gene called VCP, or valosin-containing protein,” said Traynor. However, this gene was already well-known to neurologists to cause FTD.² “That was really what piqued our interest in trying to look across the rest of the genome for other instances where you might see ALS and FTD genes that were underlying it together.”

With this in mind, the team conducted a genome-wide association study (GWAS) of ALS in Finland, which has the highest rate of ALS in the world and a relatively homogeneous population—an advantage for genetic studies.³ When examining the resulting Manhattan plots, Traynor looked for “skyscrapers,” where the height reflects the strength of association for a given single nucleotide polymorphism (SNP) and the disease. “We saw one of those skyscrapers right in chromosome nine on the short arm,” said Traynor. Because SNPs are so densely genotyped in a GWAS, the team was able to narrow the region of interest from seven million base pairs to just 100,000. Earlier linkage studies in families had also pointed to this same region.⁴

With this clearer picture, Traynor was confident the answer lay somewhere within that stretch of DNA. What he initially thought might take a few weeks, however, stretched into months—and eventually years.

Homing in On Family Trees for FTD

For Rademakers, the allure of genetics was rooted in trying to understand how this very simple code could give rise to life, but also, how just a single change in the DNA could have such profound effects and lead to disease.

Her path into the field began during her doctoral studies at the University of Antwerp, where she trained in the lab of molecular geneticist Christine Van Broeckhoven, a pioneer in early Alzheimer’s disease genetics who helped identify the first gene linked to the condition. Rademakers’s project initially set out to find Alzheimer’s disease-related genes in several families.

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As she worked to untangle these cases, Rademakers moved to the Mayo Clinic for a postdoctoral position in neuroscientist Michael Hutton’s lab, which had identified the only known gene for FTD.⁵ There, she was eager to expand her skills and continue her search for additional genetic causes. Her efforts led to the discovery of mutations in the progranulin gene, which was linked to familial FTD cases.⁶

Soon after, another opportunity reshaped her trajectory. When Hutton left the Mayo Clinic, Rademakers took over the lab in 2007. “I really got in this beautiful position. There were all these families already collected by collaborators, and those families had both FTD and ALS,” said Rademakers. It was likely that there was a common genetic defect; however, the challenge lay in finding it.

Around this time, the search had been narrowed to a region on chromosome nine as a genetic risk factor for FTD and ALS. While other studies, including Traynor’s, looked at populations, Rademakers tackled this mystery through a genealogical lens, focusing on the families within her collaborative network and collecting DNA from large multi-generational families.

One of her collaborators was Traynor, who had reached out. “They said that they could do a new method where they would sequence the entire chromosome nine from the beginning till the end, but they preferred to do this in a family, rather than their population-based study,” she said. Although they did not identify a single letter change, or point mutation, Rademakers and Traynor stayed in contact, updating each other while working separately.

A Hexanucleotide Repeat Expansion Hiding in Plain Sight

The road to a breakthrough was long and difficult, but Rademaker and Traynor persisted. After years of scouring chromosome nine, the two groups independently made a key discovery.^7,8 In 2011, both researchers realized they had been looking in the wrong place. With conventional sequencing, the researchers had been looking at protein-coding regions. However, by using new techniques such as next-generation genomic sequencing and repeat-primed PCR, they approached chromosome nine with a different lens.

Instead of a single-letter mutation, the culprit was a repeating sequence of six DNA letters—GGGGCC—located in the chromosome nine open reading frame 72 (C9orf72) gene. This region does not code for a protein, but rather it regulates how much of the protein is made. In healthy individuals, this sequence appears just a few times. In patients, it expands dramatically, repeating hundreds or even thousands of times; in turn, this leads to a buildup of toxic RNA and proteins in neurons.⁹

At the time, this kind of hexanucleotide repeat expansion had not been associated with neurodegenerative diseases like ALS or FTD. “It didn’t cross our minds that it could be something like that,” Rademakers said.

Not only did the researchers identify this C9orf72 repeat expansion, but they found that the mutation accounts for roughly a third of familial cases of both diseases in European populations and that it occurs in five percent of people with no family history. At last, they pinpointed the most common cause for both debilitating diseases.

“That's the beauty of genetics. We actually study the cause of the disease…If you find the small mistake in the DNA, then there's going to be a long time before we can understand exactly how that small change leads to disease. But if we can find it out, then it's a huge opportunity to develop a treatment,” said Rademakers.

Forging a New Path for ALS and FTD Research

With this discovery, clinicians can use genetic testing to inform patients and their family members whether they carry the mutation, while also giving researchers a clearer target for therapeutic development.

“The thing that most excites me at the moment is we’ve got a clinical trial ongoing…in patients carrying just this single mutation,” said Traynor. To support this effort, Traynor and his team conducted a drug-repurposing screen based on relevant genetic variants to identify potential treatments. One candidate that emerged was acamprosate, which, in cell models, showed efficacy comparable to the current standard of care.¹⁰ Traynor also hopes to pair these advances with a newly developed blood test for ALS.¹¹ This test measures a distinct set of proteins and may be capable of detecting the disease up to a decade before symptoms appear.

Overall, this collective work highlights the determination, perseverance, and collaboration required to make progress against complex neurodegenerative diseases. ALS and FTD, which were once thought to be entirely separate, are now understood to exist along a spectrum, with overlapping genetic and biological causes.

Although both diseases remain incurable, these insights are already helping clinicians provide clearer information to patients and their families. More importantly, they are laying the groundwork for a future in which earlier diagnosis and targeted therapies could fundamentally change how physicians like Traynor treat these conditions.

“We are doing amazing things, and not just talking about our lab, I'm talking about all of the labs across the world working on ALS and FTD, and I really do think we are really entering into that golden era of medicine and neurology,” said Traynor.