Targeting TDP-43 to improve diagnosis and treatment for ALS and frontotemporal dementia

TDP-43 Proteinopathy in ALS-FTD: Mechanism, Target Validation and Biomarker

NIH-funded research Johns Hopkins University · NIH-10809790

Researchers are developing a gene therapy and an early blood test for adults with ALS or frontotemporal dementia linked to TDP-43 problems.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionJohns Hopkins University NIH-funded
Lab location1 site (Baltimore, United States)
Project IDNIH-10809790 on NIH RePORTER

What this research studies

This project aims to understand how TDP-43 causes nerve cell damage in ALS and FTD and to test a new AAV9 gene therapy approach. The team is creating monoclonal antibodies that detect abnormal peptides produced when TDP-43 stops doing its normal job, which could become a prognostic blood test that finds disease before symptoms. They will work with patient samples, including people who carry the C9ORF72 genetic change, and use laboratory models to define a safe and effective treatment window. If you take part, you may be asked to give blood or other samples and to visit Johns Hopkins for evaluations.

Who could benefit from this research

Good fit: Adults with ALS or frontotemporal dementia, and people known to carry ALS-linked mutations such as C9ORF72, would be the most relevant candidates for participation.

Not a fit: People whose symptoms are caused by conditions unrelated to TDP-43, individuals under 21, or those unable to undergo gene-therapy procedures are less likely to benefit from this work.

Why it matters

Potential benefit: If successful, this work could allow earlier diagnosis of ALS and FTD and lead to a gene therapy that slows or prevents disease progression.

How similar studies have performed: AAV9 gene delivery has shown success in other motor neuron disorders, but applying this approach to TDP-43 driven ALS-FTD and using cryptic-exon antibodies as a biomarker is largely experimental.

Where this research is happening

Baltimore, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions Alzheimer disease dementiaAlzheimer syndrome
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.