Impact

Imagine a loved one – your spouse, sibling, parent – transformed into an entirely different person right before your eyes. Once pleasant and warm, they become aggressive and volatile and engage in completely uncharacteristic behaviors. Frontotemporal dementia (FTD) is a devastating neurodegenerative disease that completely alters an individual’s personality and behavior, often in the prime of their lives. Unlike Alzheimer’s disease, which is typically diagnosed after the age of 65, FTD is often diagnosed between the ages of 45 and 65 and is marked by progressive and rapid nerve cell loss in the frontal or temporal lobes of the brain. This neuronal loss impacts memory, personality, behavior, language, and movement.

A subset of people with FTD have an inherited form of disease caused by mutations in the GRN gene, which codes for the protein progranulin. Progranulin is a protein known to play a key role in lysosomal function and innate immunity in the brain. Progranulin is targeted to lysosomes where it is processed into its biologically active subunits, granulins, which are responsible for maintaining normal lysosomal function. People who have an FTD-GRN mutation in one allele fail to produce sufficient progranulin, impacting the production of granulins in neuronal lysosomes, triggering progressive neuronal deterioration and eventually death. These individuals typically begin developing symptoms in their 50s and rapidly decline thereafter, with death occurring 5-10 years after the onset of symptoms.

While there are no current approved treatment options, new insights into the biology of disease are guiding experts to discover new therapies with the potential to delay the onset of symptoms and slow disease progression.