Phase 1-2 open-label, multiple-dose, dose-escalation study to evaluate the safety and tolerability of intravenous infusion of SNS01-T, a first-in-class modulator of eukaryotic translation initiation factor 5A (eIF5A) in patients (pts) with relapsed or refractory B-cell malignancies.

Craig, Michael; Bensinger, William I.; Siegel, David S.; Rhee, Frits van; Novitzky, Nicolás; McDonald, Andrew; Gutierrez, Martin; Libby, Edward N.; Thompson, John E.; Bexon, Alice; Barranco, Charles; Taylor, Catherine A.; Dondero, Richard; Browne, Leslie J.; Kurman, Michael R.; Lust, John A.

doi:10.1200/jco.2014.32.15_suppl.tps8616

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 49 Likewise, targeting eIF5A is under investigation for treating several human cancers 50 and the safety and tolerability of intravenous infusion of chemical inhibitor of eIF5A have already been evaluated in Phase I–II in patients with relapsed or refractory B-cell malignancies. 51 Taking advantage of the clinical data on pharmacokinetics, toxicity, safety and tolerability (e.g. knowledge of the absence of dose limiting toxicities, DLTs) would serve as basis in shaping the direction of novel “drug repurposing/repositioning” research study, in which a clinically approved drug is investigated for a novel application that is for the present application of its therapeutic potential in ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of eIF5A hypusination pathway as a new pharmacological target for stroke therapy

Bourourou

Gouix

Melis

et al. 2020

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

In eukaryotes, the polyamine pathway generates spermidine that activates the hypusination of the translation factor eukaryotic initiation factor 5A (eIF5A). Hypusinated-eIF5A modulates translation, elongation, termination and mitochondrial function. Evidence in model organisms like drosophila suggests that targeting polyamines synthesis might be of interest against ischemia. However, the potential of targeting eIF5A hypusination in stroke, the major therapeutic challenge specific to ischemia, is currently unknown. Using in vitro models of ischemic-related stress, we documented that GC7, a specific inhibitor of a key enzyme in the eIF5A activation pathway, affords neuronal protection. We identified the preservation of mitochondrial function and thereby the prevention of toxic ROS generation as major processes of GC7 protection. To represent a thoughtful opportunity of clinical translation, we explored whether GC7 administration reduces the infarct volume and functional deficits in an in vivo transient focal cerebral ischemia (tFCI) model in mice. A single GC7 pre- or post-treatment significantly reduces the infarct volume post-stroke. Moreover, GC7-post-treatment significantly improves mouse performance in the rotarod and Morris water-maze, highlighting beneficial effects on motor and cognitive post-stroke deficits. Our results identify the targeting of the polyamine-eIF5A-hypusine axis as a new therapeutic opportunity and new paradigm of research in stroke and ischemic diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of eIF5A hypusination pathway as a new pharmacological target for stroke therapy

Bourourou

Gouix

Melis

et al. 2020

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…In addition, a proprietary linear PEI derivative named JetPEIs is available commercially, which allows in vitro and in vivo transfection of various RNAs in a relatively safe manner (Urban-Klein et al, 2005;Höbel and Aigner, 2013). Notably, SNS01-T, an in vivo-JetPEI-based nanoparticle formulation for codelivery of siRNA and plasmid targeting EIF5A, has entered phase I/II clinical trials (NCT01435720) for treatment of B-cell lymphoma (Craig et al, 2014).…”

Section: Poly (Ethyleneimine) and Its Derivativesmentioning

confidence: 99%