Skip Navigation

Jean-Pierre Julien, PhD

flower close-up

Jean-Pierre Julien, PhD

Laval University, Quebec

Intrabody-based therapy to inhibit TDP-43 interaction with p65 NF-κB

We discovered that an upregulation of TDP-43 in ALS acts as co-activator of nuclear factor-κB (NF-κB) and that this interaction can induce hyperactivity of NF-κB resulting in exaggerated innate immune responses and increased neuronal vulnerability to toxic environment. Here we propose to develop a therapeutic approach based on expression of nuclear intrabodies (antibodies that work inside the cell) against TDP-43 to specifically block its interaction with NF-κB p65. We have generated a hybrid cell line that produces monoclonal antibodies against the RRM1 domain of TDP-43. From these cell lines, we will derive cDNAs encoding single chain antibodies (scFv) that will be used to generate an adeno-associated virus. This virus will encode intrabodies aiming to block TDP-43 interaction with p65 in the nucleus and to alleviate protein aggregation.

 

return to project list

Steven Finkbeiner

Our Experts

Gladstone Institutes, UCSF
Two recently discovered genes that have been associated with both familial and sporadic forms of ALS encode the related proteins TDP43 and FUS cause neuron death in ALS.
Meet Our Experts