Using cell 'import' proteins to clear harmful TDP-43 clumps in dementia and ALS
Nuclear import receptors as modifiers of TDP-43 phase transition and toxicity in FTD/ALS
['FUNDING_R01'] · MAYO CLINIC JACKSONVILLE · NIH-11234295
This work looks at whether natural cell proteins called nuclear-import receptors can help remove sticky TDP‑43 protein clumps that damage nerve cells in frontotemporal dementia, ALS, and some Alzheimer-related dementias.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | MAYO CLINIC JACKSONVILLE (nih funded) |
| Locations | 1 site (JACKSONVILLE, UNITED STATES) |
| Trial ID | NIH-11234295 on ClinicalTrials.gov |
What this research studies
From a patient perspective, the team studies how TDP‑43, a protein that can form harmful clumps in nerve cells, gets stuck outside the cell nucleus and how that leads to damage. They focus on nuclear-import receptors (NIRs), which may act like molecular helpers to pull TDP‑43 back into the nucleus and dissolve aggregates. The work uses lab-grown cells and animal models to see if NIRs can reverse mislocalization and restore normal TDP‑43 function. The ultimate aim is to use those findings to guide the development of new treatments targeting TDP‑43 across several dementias and ALS.
Who could benefit from this research
Good fit: People diagnosed with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or Alzheimer-related dementia who are suspected to have TDP‑43 protein involvement would be the most relevant candidates for related patient studies or sample donation.
Not a fit: Patients whose disease is driven only by other pathologies (for example, pure amyloid or tau without TDP‑43) or those in very advanced stages may not benefit from therapies targeting TDP‑43.
Why it matters
Potential benefit: If successful, this could lead to therapies that clear TDP‑43 aggregates and protect nerve cells, potentially slowing or preventing progression in FTD, ALS, and some Alzheimer-related dementias.
How similar studies have performed: Preclinical work in cells and animal models from these labs and others shows promising reversal of TDP‑43 aggregation with NIRs, but this approach has not yet been tested in people.
Where this research is happening
JACKSONVILLE, UNITED STATES
- MAYO CLINIC JACKSONVILLE — JACKSONVILLE, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: ROSSOLL, WILFRIED — MAYO CLINIC JACKSONVILLE
- Study coordinator: ROSSOLL, WILFRIED
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions: Alzheimer disease dementia, Alzheimer syndrome, Alzheimer's Disease, Alzheimer's Disease and its related dementias