People may remember nasopharyngeal swabs as a feature of COVID-19 diagnostics. The deep swabs were used early on in the pandemic, before shallower swabs became available. But for researchers at biotech start-up Crownlands, which emerges from stealth today, the nasopharynx offers a very different diagnostic insight: a peek at the molecular state of a live person’s brain.
“We call it living neuroscience,” says Crownlands cofounder and CEO Nate Dalva, who hopes the company’s unique approach to noninvasive patient data collection will fuel future drug discovery in neurodegeneration.
Nestled in a cavity high in the nose is the olfactory epithelium—a patch of neurons, glia, and specialized immune cells. Researchers have found that these cells have a lot in common with neurons in the brain. For example, olfactory tissue from people with Alzheimer’s disease shows the same amyloid-β aggregates as are found within the brain. But unlike brain cells, olfactory neurons regenerate.
“They’re constantly turning over through life, which means that . . . we can go back and sample longitudinally,” says cofounder and head of discovery Kevin Zhu.
The trouble is, the cells are difficult to collect, even for expert physicians. So Crownlands researchers developed a specialized swab to flex through the nasal passageway and reach the olfactory epithelium more reliably.
“Our business model is building very large, longitudinal datasets.”
The researchers have collected and sequenced samples from 202 people participating in clinical studies, including healthy volunteers and a handful of people who have been diagnosed with Alzheimer’s or Parkinson’s disease. Today, they release a transcriptomic atlas of the tissue: a dataset comprising single-cell transcriptomes from 4 million cells. The company also has a publicly available chatbot to help researchers, or the casually interested public, explore the data.
In a preprint (PDF), which has not been peer reviewed, Zhu, Dalva, and colleagues report that the olfactory neurons offer a closer match to gene expression patterns in the brain than other clinically accessible samples like cerebrospinal fluid or blood. (The cells showed a very slight advantage over neurons derived from induced pluripotent stem cells, another approach neuroscientists often use to model what’s going on in a living person’s brain.)
In an analysis of samples from five people with Alzheimer’s and five with Parkinson’s disease, the researchers found well-known biomarkers of each disease in olfactory tissue.
Crownlands scientists are continuing to collect observational data from a clinical study on Alzheimer’s disease. “Our business model is building very large, longitudinal datasets,” Dalva says. He hopes such data, analyzed with artificial intelligence, may offer insight into risk factors for neurodegenerative diseases, biomarkers for their progression, and ways to sharpen clinical trials to enroll the people most likely to benefit.
Founded in 2024, Crownlands has raised an undisclosed sum from venture capital firms including Caffeinated Capital, First Round Capital Holdings, and Scribble Ventures.
