Discovery

Northwestern University receives USD 1.84m NIH grant for tauopathy gene therapy development

Northwestern University has received a USD 1.84 million NIH RF1 grant from the National Institute of Neurological Disorders and Stroke to advance preclinical gene therapy development for tauopathies, a disease category that encompasses Alzheimer's disease, frontotemporal dementia, and progressive supranuclear palsy.

The award, issued in May 2026 and running through March 2029, supports work led by John A. Kessler in Northwestern's neurology department. The RF1 mechanism signals NINDS support for research with a defined translational trajectory rather than open-ended discovery.

The science behind BMP signaling and tau pathology

The project centers on bone morphogenetic protein signaling, which increases in the aging brain and appears to drive tau hyperphosphorylation across multiple disease contexts. Prior work from the Kessler laboratory demonstrated that noggin, a BMP inhibitor, reduced tau phosphorylation in iPSC-derived human neurons from both FTD and Alzheimer's disease backgrounds, and that noggin overexpression prevented neuropathological changes and behavioral abnormalities in two distinct mouse models — a P301S tauopathy model and an APOE4 knockin model. Postmortem human brain data were also consistent with the hypothesis.

The funded project aims to develop a clinically translatable AAV vector strategy for noggin overexpression, building on that preclinical evidence base.

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Translational relevance

The BMP pathway has not been a primary focus of the tau therapeutics field, which has largely concentrated on tau aggregation inhibitors, antisense oligonucleotides targeting tau expression, and active or passive immunotherapy approaches. The Kessler group's data positioning BMP inhibition upstream of tau phosphorylation offers a mechanistically distinct entry point, and the use of AAV vectors aligns with delivery approaches already in clinical use for other neurological indications. NINDS funding through an RF1 award, which is structured to support research with explicit translational intent, reflects the agency's assessment that the preclinical rationale warrants further development investment.


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