Podcast recap: Wanda Smith on turning a family diagnosis into CureGRN
In last week’s episode of The Genetics Podcast, Patrick Short sat down with Wanda Smith, founder of CureGRN and long-time advocate for families affected by progranulin-related frontotemporal dementia (FTD). Wanda has spent decades helping brain and plasma banks, connecting with scientists, and helping families. In this blog, we cover how Wanda became involved with FTD and the impact of her work.
From misdiagnosis to discovery
Wanda’s journey began in the 1980s when her mother developed early behavioral changes at the age of 52. Multiple neurologists diagnosed her with Alzheimer’s, but an autopsy later showed no plaques or tangles in the brain. That mismatch set Wanda on an 18 year push to find others, bank samples, and partner with researchers.
Those efforts helped power the 2006 discovery that loss of function variants in the GRN gene cause a form of FTD. Within weeks of the gene discovery, her family’s specific mutation was identified. The focus shifted from unexplained dementia to a defined biology that could be measured, tracked, and treated.
Progranulin biology
GRN is a haploinsufficient gene. One healthy copy is not enough to produce the progranulin protein levels cells need. Lower progranulin disrupts lysosomal function and protein clearance and over time this can lead to FTD.
Researchers have also uncovered important modifiers and partners. TMEM106B appears to modify risk and age of onset in some families, and sortilin regulates how progranulin is trafficked inside cells. These insights are informing several therapeutic strategies.
The therapeutic pipeline
Six clinical programs are active today, with more in preclinical development. Approaches include small molecules that change progranulin processing, biologics that target sortilin and related pathways, and AAV-based gene therapies that aim to restore progranulin production in the brain.
Readouts begin as early as this year, and success in any one approach could lift the entire neurodegeneration field. Progranulin also shows signals across other conditions, including Alzheimer’s, Parkinson’s, and Lewy body disease, so the upside extends beyond GRN FTD.
Diagnosis, genetics, and biomarkers
The current diagnostic path is too slow and too dependent on symptoms. Many families see multiple clinicians over several years before anyone orders a genetic test. By then, brain imaging can still look normal while behavior, language, and motor changes are clear.
Wanda argues for flipping the order. Get genetics and simple blood biomarkers earlier, then layer imaging and specialty workups as needed. Neurofilament light in blood and cerebrospinal fluid (CSF) is a useful inflammation and neurodegeneration marker, and blood progranulin levels can help identify likely GRN carriers. Earlier answers open the door to prevention trials and more precise care plans.
Stigma, access, and real world barriers
Families face stigma, worry about labels, and concerns about insurance, employment, and long term care. Wanda explains that the language we use matters. Moving from symptom labels to biology can help reduce shame and increase participation in research and care.
Education and repetition across multiple channels are key. Some families want live groups and direct contact, while others prefer to learn privately first. CureGRN builds for both, and links people to strong partners like AFTD for helplines, genetic counseling, and support groups.
A global network
Progress depends on a wide net. Wanda and CureGRN collaborate with GENFI in Europe and emerging centers in India and beyond. As more sites adopt consistent genetic testing and data sharing, recruitment speeds up, trials reach the right people sooner, and evidence builds faster.
Looking ahead
Wanda has a clear and positive vision of what the near future could look like if certain roadblocks are removed. If one of the current programs slows or halts disease, the care model should shift. Genetics needs to move earlier in the pathway, and coverage and reimbursement need to be aligned with adapting needs. Recruitment into prevention studies needs to start well before symptoms.
For Wanda, success would not only change the trajectory for families with GRN mutations but also reshape the broader neurodegenerative field. It would prove that earlier testing and intervention can work, encourage more investment beyond amyloid in Alzheimer’s, and build a foundation for prevention across the wider TDP-43 spectrum.
Listen to the full episode below.