Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a Phase I open-label dose escalation study

Laham, Roger J.; Chronos, N.; Pike, Marilyn C.; Leimbach, Mark E.; Udelson, James E.; Pearlman, Justin D.; Pettigrew, Roderic I.; Whitehouse, M. J.; Yoshizawa, Carl N.; Simons, Michael

doi:10.1016/s0735-1097(00)00988-8

Cited by 204 publications

(108 citation statements)

References 43 publications

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“…Given that stress-induced relapse is a significant problem in the treatment of anxiety disorders, the finding that FGF2 reduces reinstatement has potentially important clinical implications. Although FGF2 has been trialed in humans as a potential inducer of angiogenesis (Laham et al, 2000;Lederman et al, 2002;Simons et al, 2002), until now it has not been considered as a potential pharmacological adjunct to exposure therapy.…”

Section: Discussionmentioning

confidence: 99%

Acute Systemic Fibroblast Growth Factor-2 Enhances Long-Term Extinction of Fear and Reduces Reinstatement in Rats

Graham

Richardson

2009

Neuropsychopharmacol

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Despite having made substantial advances in the treatment of anxiety disorders over the past few decades it appears that we have now reached a 'therapeutic impasse'. Further clinical progress requires a greater understanding of the neural mechanisms underlying fear inhibition. In this study, we examined, for the first time, the effects of fibroblast growth factor-2 (FGF2), a mitogen involved in the molecular cascade of memory, on extinction and relapse in rats. In all experiments, rats were first trained to fear a white noiseconditioned stimulus, and then had this learned fear extinguished the following day. Extinction is the process underlying exposure-based therapy in humans. Experiments 1 and 2 demonstrated that FGF2 facilitated the loss of learned fear (ie, extinction) when given either prior to or immediately after extinction but not when given 4 h after extinction. This suggests that FGF2 must be present during the consolidation of the extinction memory to have an effect. Experiment 3 further supported this interpretation by showing that short-term extinction must occur for FGF2 to facilitate long-term extinction, suggesting that FGF2 is facilitating the translation of memory from short-term to long-term storage. In experiment 4 rats given FGF2 immediately after extinction exhibited less shock-induced reinstatement, which is a model preparation of relapse, than did vehicle-treated rats. Together, these experiments demonstrate that FGF2 facilitates extinction and attenuates relapse. Thus, FGF2 may be a novel pharmacological adjunct to exposure therapy.

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Section: Discussionmentioning

confidence: 99%

Acute Systemic Fibroblast Growth Factor-2 Enhances Long-Term Extinction of Fear and Reduces Reinstatement in Rats

Graham

Richardson

2009

Neuropsychopharmacol

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“…factor (bFGF or FGF-2) and vascular endothelial growth factor (VEGF), are being studied as a safe and potentially effective therapy to reduce myocardial ischemia either in conjunction with bypass surgery or percutaneous catheter-based recanalization, or as a monotherapy in "no option" patients [1][2][3]. All the current strategies involve invasive approaches in high-risk patients to deliver the growth factors locally.…”

Section: Arious Growth Factors Such As Basic Fibroblast Growthmentioning

confidence: 99%

Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia

Sato

Laham

Pearlman

et al. 2000

The Annals of Thoracic Surgery

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“…5,6 Sensitive noninvasive imaging techniques providing regional assessment of blood flow such as positron emission tomography and MRI may overcome this problem in preclinical studies, and are already being evaluated in clinical angiogenesis trials. [14][15][16] In conclusion, plasmid VEGF 165 delivery by direct intramyocardial injection to the pig myocardium improves regional perfusion but only in areas adjacent to the site of administration into a region of ischaemia.…”

Section: Angiographic Assessment After Pvegf 165 Transfermentioning

confidence: 87%

Effects of intramyocardial pVEGF165 delivery on regional myocardial blood flow: evidence for a spatial ‘delivery–efficacy’ mismatch

et al. 2004

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Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a Phase I open-label dose escalation study

Abstract: Intracoronary administration of rFGF-2 appears safe and is well tolerated over a 100-fold dose range (0.33 to 0.36 microk/kg). Preliminary evidence of efficacy is tempered by the open-label uncontrolled design of the study.

Cited by 204 publications

References 43 publications

Acute Systemic Fibroblast Growth Factor-2 Enhances Long-Term Extinction of Fear and Reduces Reinstatement in Rats

Acute Systemic Fibroblast Growth Factor-2 Enhances Long-Term Extinction of Fear and Reduces Reinstatement in Rats

Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia

Effects of intramyocardial pVEGF165 delivery on regional myocardial blood flow: evidence for a spatial ‘delivery–efficacy’ mismatch

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