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 Pharmacokinetic / Pharmacodynamic-Based Rationale for Dose Selection of the TPH Inhibitor Rodatristat Ethyl in ELEVATE2 – a Phase 2b Study in Pulmonary Arterial Hypertension
May 14, 2021
American Thoracic Society Annual Meeting
Tissue Distribution And Biomarker Data For Rodatristat, A Novel Serotonin (5-HT) Synthesis Inhibitor For PAH, Demonstrate Negligible Blood-brain Barrier Penetration And Pharmacologically Meaningful Exposure In Lung
August 5, 2020
American Thoracic Society Annual Meeting
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
Once Daily Oral Dosing of RodatristatEthyl (RVT-1201) Achieves Reductions in Serotonin Biosynthesis Comparable to Those Associated with Reversal of Vascular Remodeling in PAH Animal Models
22 October 2019
CHEST Annual Meeting; New Orleans, LA
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
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
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
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.
Tryptophan Hydroxylase (TPH) Platform Publications
The Serotonin Hypothesis of PAH – Reviews
Recent advances in pulmonary arterial hypertension
F1000Res. 2018 Jul 24;7.
The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series)
Pulm Circ. 2018 Apr-Jun;8(2):2045894018759125.
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.
Review of the Ongoing Story of Appetite Suppressants, Serotonin Pathway, and Pulmonary Vascular Disease
Am J Cardiol. 2016 May 15;117(10):1691-1696.
The serotonin hypothesis of pulmonary hypertension revisited
Adv Exp Med Biol. 2010;661:309-22.
Serotonin and pulmonary hypertension–from bench to bedside?
Curr Opin Pharmacol. 2009 Jun;9(3):281-6.
Pulmonary hypertension: therapeutic targets within the serotonin system.
Br J Pharmacol. 2008 Oct;155(4):455-62.
Peripheral Serotonin Modulation with Tph1 Inhibitors
GPCRs in pulmonary arterial hypertension: tipping the balance
Br J Pharmacol. 2018 Aug;175(15):3063-3079.
Peripheral Serotonin Synthesis as a New Drug Target
Trends Pharmacol Sci. 2018 Jun;39(6):560-572.
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.
Clinical Data Linking Serotonin to PAH
Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American pulmonary hypertension
Chest. 2000 Mar;117(3):870-4.
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.
Increased plasma serotonin in primary pulmonary hypertension
Am J Med. 1995 Sep;99(3):249-54.
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.
Gene therapy by targeted adenovirus-mediated knockdown of pulmonary endothelial Tph1 attenuates hypoxia-induced pulmonary hypertension
Mol Ther. 2012 Aug;20(8):1516-28.
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.
Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia-induced pulmonary hypertension
Hypertension. 2007 Jan;49(1):232-6.
Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension
Circ Res. 2006 May 26;98(10):1323-30.
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.
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
Airway inflammation in children and adolescents with bronchiolitis obliterans
Cytokine, 73(1), 156–162. doi: 10.1016/j.cyto.2014.10.026
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
Post-transplant bronchiolitis obliterans
European Respiratory Journal, 22(6), 1007–1018. doi: 10.1183/09031936.03.00039103
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
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
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
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.
