Huntington’s Disease: Cell ‘Tunnels’ Linked to Protein Spread & Potential New Treatment Target

BOCA RATON, FL – Researchers at Florida Atlantic University have discovered that brain cells utilize microscopic tunnels, called tunneling nanotubes, to transmit the toxic protein that causes Huntington’s disease, potentially opening new avenues for treatment of the devastating neurological disorder.

The study, published in Science Advances on March 21, 2026, details how these nanotubes act as direct connections between brain cells, allowing the harmful huntingtin protein to spread. Disrupting this pathway significantly reduced the protein’s transmission in laboratory settings and in mouse models, according to the research team.

Huntington’s disease is a rare, inherited brain disorder affecting approximately three to seven people per 100,000 worldwide, causing progressive movement, cognitive, and psychiatric symptoms. Currently, there is no cure, and existing treatments only manage symptoms without halting the disease’s progression. Individuals typically live 10 to 20 years after symptom onset, facing increasing disability.

For years, scientists have understood that the toxic protein doesn’t remain localized but spreads from cell to cell. Although, the precise mechanism of this spread remained elusive until now. The FAU research team identified a partnership between two proteins, Rhes and SLC4A7, as crucial to the formation of these tunneling nanotubes.

“This work fundamentally changes how we think about disease progression in Huntington’s,” said Srinivasa Subramaniam, Ph.D., associate professor in the Department of Chemistry and Biochemistry within FAU’s Charles E. Schmidt College of Science, and a member of FAU’s Stiles-Nicholson Brain Institute. “We’ve known that neurons somehow pass toxic proteins to one another, but now People can see the machinery that makes that possible. By identifying SLC4A7 as a key partner of Rhes, we’ve uncovered a new and potentially druggable target to stop that spread at its source.”

The researchers found that Rhes physically binds to SLC4A7 at the cell membrane, triggering changes that promote nanotube growth. Blocking SLC4A7, either genetically or with drugs, prevented nanotube formation and significantly reduced the spread of the toxic huntingtin protein. This effect was observed not only in isolated cells but also in mouse models of Huntington’s disease, where a reduction in protein transfer was seen in the brain’s striatum, the region most affected by the disease.

Randy Blakely, Ph.D., executive director of the FAU Stiles-Nicholson Brain Institute, emphasized the broader implications of the discovery. “This research shines a spotlight on an entirely new way cells communicate in health and disease. By learning how harmful proteins physically move from cell to cell, we gain powerful new leverage points for therapy. The idea that we could slow or even halt disease progression by blocking these microscopic tunnels opens an exciting frontier for treating not only Huntington’s disease, but a wide range of neurological disorders and cancers in the future.”

Tunneling nanotubes have also been implicated in other neurodegenerative disorders, including those involving tau protein, and in cancer, where tumor cells utilize similar structures to share signals and drug resistance. The involvement of Rhes and SLC4A7 in fundamental cellular processes suggests this pathway may be a common mechanism underlying damage spread in multiple diseases.

The study involved collaboration with researchers from the Facultad de Ciencias, National Autonomous University of Mexico. Institute of Cellular Physiology, National Autonomous University of Mexico; Max Planck Florida Institute for Neuroscience; and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology.