Researchers from DANDRITE (Danish Research Institute of Translational Neuroscience) have played a leading role in developing a new oral treatment that may both prevent and slow the progression of frontotemporal dementia (FTD). For the first time, a clinical trial in patients has shown that the therapy can restore normal levels of the protein progranulin in individuals carrying a genetic mutation linked to this severe neurodegenerative disease.
“This means we now have hope for a treatment that could potentially prevent the development of this form of dementia in people at genetic risk—thereby conceptually transforming the future of dementia therapy,” said Professor Anders Nykjær, one of the principal investigators behind the discovery.
Danish Researchers Unlock Key Mechanism Behind Dementia Development
Professor Nykjær and his colleagues were among the first to uncover how the sortilin receptor regulates the degradation of progranulin in nerve cells—a process that plays a central role in the onset of FTD.
“For several years, we have been studying the role of the sortilin receptor in neurodegeneration,” Nykjær explained. “Seeing this knowledge translated into a treatment that now shows promising clinical results is a major step forward—and a testament to the importance of basic research in developing new therapies.”
Understanding Frontotemporal Dementia and Its Rapid Progression
Frontotemporal dementia is the most common cause of dementia in people under 60 years of age. It leads to changes in behavior, personality, and language, progressing much faster than Alzheimer’s disease. Currently, no approved treatments exist to halt or slow its development.
The condition has gained public attention after actor Bruce Willis revealed his diagnosis, helping to raise awareness of its impact on younger adults.
Innovative Oral Treatment Targets Dementia-Causing Protein Pathway
The new therapy, known as VES001, was developed by Vesper Bio, a Danish biotechnology company co-founded by Anders Nykjær and Mads Kjølby. The drug works by inhibiting the sortilin receptor, preventing the breakdown of progranulin and thereby restoring its protective function in brain cells—without disrupting other essential neurological processes.
In the completed Phase Ib/IIa clinical trial, patients carrying GRN gene mutations—which cause a specific form of FTD known as FTD-GRN—showed a normalization of progranulin levels in the cerebrospinal fluid.
The treatment also displayed a favorable safety profile, with no serious adverse effects in participants who had not yet developed symptoms of the disease.
Frontotemporal Dementia Linked to Genetic Mutation (FTD-GRN)
FTD-GRN is a subtype of frontotemporal dementia caused by mutations in the progranulin gene (GRN). These mutations result in significantly reduced levels of progranulin, a protein vital for maintaining neuronal health.
By restoring progranulin production, VES001 aims to protect brain cells from degeneration—potentially preventing the onset of dementia symptoms altogether.
Clinical Findings Mark a Turning Point in Dementia Research
According to results from the Phase Ib/IIa study, treatment with VES001 increased progranulin levels by more than 95% in cerebrospinal fluid. Researchers emphasized that this is the first time an oral treatment has achieved such normalization in individuals with GRN mutations.
“These findings represent a conceptual breakthrough,” said Nykjær. “We may finally be able to intervene before irreversible brain damage occurs.”
Danish Science at the Forefront of Dementia Innovation
The success of VES001 highlights the pivotal role of Danish neuroscience research in uncovering the mechanisms that drive dementia. By translating fundamental biological discoveries into targeted therapies, Danish scientists have contributed to one of the most promising advances in the field to date.
“Basic research is the foundation of all medical breakthroughs,” Nykjær concluded. “This treatment demonstrates how decades of fundamental studies can lead directly to new hope for patients and families affected by dementia.”
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