LINKS: Rodatristat Publications ALTA-2530 Publications Other Publications

Modulation of Serotonin in PAH

Professor Mandy MacLean, University of Glasgow Scotland
PVRI – Pulmonary Vascular Research Institute

Rodatristat Ethyl Publications 

A Trial Design to Maximize Knowledge of the Effects of Rodatristat Ethyl in the Treatment of Pulmonary Arterial Hypertension (ELEVATE 2)

29 April 2022

Pulmonary Circulation 2022; 12:e12088

Lazarus HM, Denning J, Wring S, Palacios M, Hoffman S, Crizer K, Kamau-Kelley W, Symonds W, Feldman J

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ELEVATE 2: A Multicenter Study of Rodatristat Ethyl in Patients with WHO Group 1 Pulmonary Arterial Hypertension

13 September 2021

European Respiratory Society Annual Congress

Lazarus HM, Denning J, Kamau-Kelley W, Wring S, Palacios M, Humbert M

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Rodatristat is Metabolically Stable and Has Low Potential for Drug Interactions with PAH Medications

February 2020

PVRI World Congress on Pulmonary Vascular Disease; Lima, Peru

Palacios M, Crizer K, Gaukel, E, and Wring S

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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Repeated Once or Twice Daily RVT-1201, a TPH Inhibitor for Treatment of PAH

1 October 2019

European Respiratory Society International Congress; Madrid, Spain

Wring S, Rurka J, Crizer KR, Palacios M, Snyder M, Keller L, Evans P, Carpenter D

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Optimization and Validation of a LC-MS/MS Method for Peripheral Serotonin (5-HT) as a Pharmacodynamic Biomarker of Treatment with Tryptophan Hydroxylase Inhibitors

3 June 2019

67th Conference on Mass Spectrometry and Allied Topics; Atlanta, GA

Crizer KR, Viel F, Thibault FS, Palacios M, Wring S

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Translational Analysis of RVT-1201 Nonclinical and Clinical Pharmacokinetic and Pharmacodynamic Biomarker Data to Predict Clinical Dose of a Novel TPH Inhibitor for Treatment of Pulmonary Arterial Hypertension

2 February 2019

3th PVRI Annual World Congress on PVD; Barcelona, Spain

Wring S, Alonso-Galicia M, Crizer KR, Gaukel E, Holman N, Pack T, Palacios M, Rurka J, Carpenter D, Rhodes M.

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Tryptophan hydroxylase 1 Inhibition Impacts Pulmonary Vascular Remodeling in Two Rat Models of Pulmonary Hypertension

1 February 2017

J Pharmacol Exp Ther. 2017 Feb;360(2):267-279.

Aiello RJ, Bourassa PA, Zhang Q, Dubins J, Goldberg DR, De Lombaert S, Humbert M, Guignabert C, Cavasin MA, McKinsey TA, Paralkar V

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Tryptophan Hydroxylase (TPH) Platform Publications

The Serotonin Hypothesis of PAH – Reviews

Recent advances in pulmonary arterial hypertension

F1000Res. 2018 Jul 24;7.

Wilkins MR, Aman J, Harbaum L, Ulrich A, Wharton J, Rhodes CJ.

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Drug-induced pulmonary arterial hypertension: a primer for clinicians and scientists

Am J Physiol Lung Cell Mol Physiol. 2018 Jun 1;314(6):L967-L983.

Orcholski ME, Yuan K, Rajasingh C, Tsai H1 Shamskhou EA, Dhillon NK, Voelkel NF, Zamanian RT, de Jesus Perez VA

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Serotonin and pulmonary hypertension–from bench to bedside?

Curr Opin Pharmacol. 2009 Jun;9(3):281-6.

MacLean MR, Dempsie Y.

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Peripheral Serotonin Modulation with Tph1 Inhibitors

GPCRs in pulmonary arterial hypertension: tipping the balance

Br J Pharmacol. 2018 Aug;175(15):3063-3079.

Iyinikkel J, Murray F.

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Peripheral Serotonin Synthesis as a New Drug Target

Trends Pharmacol Sci. 2018 Jun;39(6):560-572.

Matthes S, Bader M.

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Tryptophan Hydroxylase 1 Inhibition Impacts Pulmonary Vascular Remodeling in Two Rat Models of Pulmonary Hypertension

J Pharmacol Exp Ther. 2017 Feb;360(2):267-279.

Aiello RJ, Bourassa PA, Zhang Q, Dubins J, Goldberg DR, De Lombaert S, Humbert M, Guignabert C, Cavasin MA, McKinsey TA, Paralkar V.

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Clinical Data Linking Serotonin to PAH

Appetite-suppressant drugs and the risk of primary pulmonary hypertension

International Primary Pulmonary Hypertension Study Group. N Engl J Med. 1996 Aug 29;335(9):609-16.

Abenhaim L, Moride Y, Brenot F, Rich S, Benichou J, Kurz X, Higenbottam T, Oakley C, Wouters E, Aubier M, Simonneau G, Bégaud B.

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Increased plasma serotonin in primary pulmonary hypertension

Am J Med. 1995 Sep;99(3):249-54.

Hervé P, Launay JM, Scrobohaci ML, Brenot F, Simonneau G, Petitpretz P, Poubeau P, Cerrina J, Duroux P, Drouet L.

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Preclinical Data Linking Serotonin to PAH

Imatinib attenuates hypoxia-induced pulmonary arterial hypertension pathology via reduction in 5-hydroxytryptamine through inhibition of tryptophan hydroxylase 1 expression

Am J Respir Crit Care Med. 2013 Jan 1;187(1):78-89.

Ciuclan L, Hussey MJ, Burton V, Good R, Duggan N, Beach S, Jones P, Fox R, Clay I, Bonneau O, Konstantinova I, Pearce A, Rowlands DJ, Jarai G, Westwick J, MacLean MR, Thomas M.

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Gene therapy by targeted adenovirus-mediated knockdown of pulmonary endothelial Tph1 attenuates hypoxia-induced pulmonary hypertension

Mol Ther. 2012 Aug;20(8):1516-28.

Morecroft I, White K, Caruso P, Nilsen M, Loughlin L, Alba R, Reynolds PN, Danilov SM, Baker AH, Maclean MR.

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Converging evidence in support of the serotonin hypothesis of dexfenfluramine-induced pulmonary hypertension with novel transgenic mice

Circulation. 2008 Jun 3;117(22):2928-37.

Dempsie Y, Morecroft I, Welsh DJ, MacRitchie NA, Herold N, Loughlin L, Nilsen M, Peacock AJ, Harmar A, Bader M, MacLean MR.

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Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia-induced pulmonary hypertension

Hypertension. 2007 Jan;49(1):232-6.

Morecroft I, Dempsie Y, Bader M, Walther DJ, Kotnik K, Loughlin L, Nilsen M, MacLean MR.

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Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension

Circ Res. 2006 May 26;98(10):1323-30.

Guignabert C, Izikki M, Tu LI, Li Z, Zadigue P, Barlier-Mur AM, Hanoun N, Rodman D, Hamon M, Adnot S, Eddahibi S.

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Cross talk between endothelial and smooth muscle cells in pulmonary hypertension: critical role for serotonin-induced smooth muscle hyperplasia

Circulation. 2006 Apr 18;113(15):1857-64.

Eddahibi S, Guignabert C, Barlier-Mur AM, Dewachter L, Fadel E, Dartevelle P, Humbert M, Simonneau G, Hanoun N, Saurini F, Hamon M, Adnot S.

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ALTA-2530 Publications 

BOS Pathophysiology

Advances in Understanding Bronchiolitis Obliterans After Lung Transplantation

Chest, 150(1), 219–225. doi: 10.1016/j.chest.2016.04.014

Verleden, S. E., Sacreas, A., Vos, R., Vanaudenaerde, B. M., & Verleden, G. M.

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Airway inflammation in children and adolescents with bronchiolitis obliterans

Cytokine, 73(1), 156–162. doi: 10.1016/j.cyto.2014.10.026

Rosewich, M., Zissler, U. M., Kheiri, T., Voss, S., Eickmeier, O., Schulze, J., … Zielen, S.

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Immunological Link Between Primary Graft Dysfunction and Chronic Lung Allograft Rejection

The Annals of Thoracic Surgery, 86(1), 189–197. doi: 10.1016/j.athoracsur.2008.03.073

Bharat, A., Kuo, E., Steward, N., Aloush, A., Hachem, R., Trulock, E. P., … Mohanakumar, T.

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Post-transplant bronchiolitis obliterans

European Respiratory Journal, 22(6), 1007–1018. doi: 10.1183/09031936.03.00039103

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Evidence for Targeting IL-1 in BOS Pathophysiology

Modulation of NLRP3 Inflammasome through Formyl Peptide Receptor 1 (Fpr-1) Pathway as a New Therapeutic Target in Bronchiolitis Obliterans Syndrome

International Journal of Molecular Sciences, 21(6), 2144. doi: 10.3390/ijms21062144

D’Amico, R., Fusco, R., Cordaro, M., Siracusa, R., Peritore, A. F., Gugliandolo, E., … Impellizzeri, D.

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IL-1α released from damaged epithelial cells is sufficient and essential to trigger inflammatory responses in human lung fibroblasts

Mucosal Immunology, 7(3), 684–693. doi: 10.1038/mi.2013.87

Suwara, M. I., Green, N. J., Borthwick, L. A., Mann, J., Mayer-Barber, K. D., Barron, L., … Mann, D. A.

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IL-1 Family of Cytokine Signaling

Structural Basis of IL-1 Family Cytokine Signaling

Frontiers in Immunology, 10, 1412. doi: 10.3389/fimmu.2019.01412

Fields, J. K., Günther, S., & Sundberg, E. J.

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Patient Engagement Publications 

A Framework for Engaging PAH Patients in the Drug Development Process

5 September 2019 Pulmonary Hypertension Association’s Annual PH Professional Network (PHPN) Symposium; Washington, D.C.

Mascherino L.

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