Why the TDP-43 protein leaves the nucleus in ALS and FTD
RNA-based regulation of TDP-43 nuclear export in ALS/FTD
['FUNDING_R01'] · JOHNS HOPKINS UNIVERSITY · NIH-11144328
This project looks at how a protein called TDP‑43 moves out of the cell nucleus in people with ALS and frontotemporal dementia, with the goal of finding ways to stop that harmful movement.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | JOHNS HOPKINS UNIVERSITY (nih funded) |
| Locations | 1 site (BALTIMORE, UNITED STATES) |
| Trial ID | NIH-11144328 on ClinicalTrials.gov |
What this research studies
From a patient's perspective, researchers are tracing how TDP‑43 interacts with RNA and how that interaction controls whether the protein stays in the nucleus or drifts into the cell body. They use cell-based experiments, permeabilized cell assays, and molecular tools to measure TDP‑43 mobility and to test the roles of RNA-binding and export complexes like NXF1/TREX. The team also examines how energy (ATP) and displacement from RNA influence TDP‑43 leaving the nucleus. Findings could point to molecular steps that therapies might target to keep TDP‑43 in the right place.
Who could benefit from this research
Good fit: People with ALS or frontotemporal dementia, especially those with known TDP‑43–related disease or TDP‑43 genetic changes, would be the most relevant group for future related trials or sample donation.
Not a fit: Patients whose disease is driven by non‑TDP‑43 mechanisms (for example some SOD1 ALS cases) are less likely to benefit directly from findings focused on TDP‑43 export.
Why it matters
Potential benefit: If successful, this work could point to new drug targets to prevent TDP‑43 mislocalization and slow neuron loss in ALS and some forms of FTD.
How similar studies have performed: Prior research has firmly linked TDP‑43 mislocalization to ALS/FTD but the exact export mechanism is only recently being explored, so this approach builds on established findings but is still early‑stage and novel.
Where this research is happening
BALTIMORE, UNITED STATES
- JOHNS HOPKINS UNIVERSITY — BALTIMORE, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: HOKE, AHMET — JOHNS HOPKINS UNIVERSITY
- Study coordinator: HOKE, AHMET
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: Amyotrophic Lateral Sclerosis Motor Neuron Disease