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4 results on '"Jonathan LaCombe"'

1. Evaluation of the therapeutic potential of Epigallocatechin-3-gallate (EGCG) via oral gavage in young adult Down syndrome mice

Author

Charles R. Goodlett, Megan Stringer, Roshni Patel, Randall J. Roper, Jonathan LaCombe, and Joseph M. Wallace

Subjects
Down syndrome, Genotype, DYRK1A, Administration, Oral, lcsh:Medicine, Morris water navigation task, Pharmacology, complex mixtures, Article, Catechin, Oral gavage, Target validation, Learning and memory, Gene product, Mice, medicine, Animals, heterocyclic compounds, Femur, Young adult, Maze Learning, lcsh:Science, Multidisciplinary, business.industry, Body Weight, lcsh:R, food and beverages, X-Ray Microtomography, medicine.disease, In vitro, Disease Models, Animal, Treatment Outcome, Cancellous Bone, lcsh:Q, Gene expression, sense organs, Down Syndrome, Trisomy, business
Abstract

Epigallocatechin-3-gallate (EGCG) is a candidate therapeutic for Down syndrome (DS) phenotypes based on in vitro inhibition of DYRK1A, a triplicated gene product of Trisomy 21 (Ts21). Consumption of green tea extracts containing EGCG improved some cognitive and behavioral outcomes in DS mouse models and in humans with Ts21. In contrast, treatment with pure EGCG in DS mouse models did not improve neurobehavioral phenotypes. This study tested the hypothesis that 200 mg/kg/day of pure EGCG, given via oral gavage, would improve neurobehavioral and skeletal phenotypes in the Ts65Dn DS mouse model. Serum EGCG levels post-gavage were significantly higher in trisomic mice than in euploid mice. Daily EGCG gavage treatments over three weeks resulted in growth deficits in both euploid and trisomic mice. Compared to vehicle treatment, EGCG did not significantly improve behavioral performance of Ts65Dn mice in the multivariate concentric square field, balance beam, or Morris water maze tasks, but reduced swimming speed. Furthermore, EGCG resulted in reduced cortical bone structure and strength in Ts65Dn mice. These outcomes failed to support the therapeutic potential of EGCG, and the deleterious effects on growth and skeletal phenotypes underscore the need for caution in high-dose EGCG supplements as an intervention in DS.

Published
2020
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2. Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy

Author

Louis Paradis, Benoît Mâsse, Alexandra Langlois, Thomas G. Poder, Philippe Bégin, Jonathan Lacombe-Barrios, Thomas Eiwegger, Anne Des Roches, Gordon Sussman, Kerstin Killer, Hélène Leroux, Kathryn Samaan, Julia Upton, Marie-Hélène Lavergne, and Pauline Azzano

Subjects
lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Efficacy, Dose, Desensitization, Omalizumab, Oral immunotherapy, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Food allergy, Clinical endpoint, medicine, Dosing, Anti-IgE, 030304 developmental biology, Protocol (science), 0303 health sciences, Maintenance dose, business.industry, Research, General Medicine, 3. Good health, 030228 respiratory system, Safety, lcsh:RC581-607, business, medicine.drug
Abstract

Background Previous proof-of-concept studies have shown that a short course of omalizumab can safely accelerate the oral immunotherapy schedule for multiple allergens simultaneously. Considering the high cost of medication, the dose-related efficacy of omalizumab at decreasing the duration of oral immunotherapy up-dosing phase must be objectively quantified before cost–benefit analyses can be performed. The primary objective of this trial will be to compare the efficacy of 2 omalizumab dosages to placebo at decreasing time-to-maintenance dose during a symptom-driven multi-food OIT protocol. Methods A total of 90 participants aged 6 to 25 with multiple food allergies (3 or more) will be enrolled at four sites in Canada. Participants will be randomized to: (A) Omalizumab 8 mg/kg per month (n = 36); (B) Omalizumab 16 mg/kg per month (n = 36); or (C) Placebo (n = 18). Study drug will be administered at full dosage for 12 weeks, then progressively tapered at 50% dosage (8 mg/kg vs 4 mg/kg vs placebo) for 4 weeks and at 25% dosage (4 mg/kg vs 2 mg/kg vs placebo) for another 4 weeks. After a pre-treatment period of 8 weeks, participants will undergo an initial food escalation (IFE) to an OIT mix containing 3 allergens and start daily home dosing with biweekly increases until a target daily maintenance of 1500 mg protein is achieved. The amount escalated at each visit will vary based on treatment tolerance according to a standardized up-dosing algorithm. Participants will be followed for at least 12 months following the initial food escalation. The primary endpoint will be time from IFE to the target maintenance dose of 1500 mg protein. Time-to-event analytic methods, including the log-rank test, will be used to compare the 3 arms. Discussion This trial uses a novel pragmatic approach to compare OIT with omalizumab to OIT without omalizumab in a blinded manner, which allows to single out the effect of this anti-IgE medication on treatment effectiveness speed without the recourse to predetermined schedules. The innovative patient-centered up-dosing algorithm allows to maximise treatment effectiveness speed without compromising patient safety, regardless of whether the patient is on omalizumab or not. This study will also provide novel prospective data to inform on the optimal and most cost-effective dosage for this indication. Trial registration ClinicalTrials.gov, NCT04045301, Registered 5 August 2019, https://clinicaltrials.gov/ct2/show/NCT04045301

Published
2020
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3. Canadian Society of Allergy and Clinical Immunology annual scientific meeting 2016

Author

Duncan Lejtenyi, Vincent Stagg, Michael N. Fein, Young Woong Kim, Mark W. Tenn, Peter Vadas, Marylin Desjardins, David Dai, Allan B. Becker, Charlotte Miller, David Holt, Elissa M. Abrams, Jaclyn Quirt, Brenda Reid, Leman Yel, Roxane Labrosse, Daniel Suez, Dhaifallah Alotaibi, Helen Neighbour, Alex Simidchiev, Eiman Al-Selahi, Thomas V. Gerstner, Mary Messieh, Sanju Mishra, Edward M. Conway, Lucy Duan, Xichun Sun, Amin S. Kanani, Chaim M. Roifman, Mark Stein, Delia Heroux, ChenXi Yang, Chrystyna Kalicinsky, Chun T. Che, Barbara McCoy, Louis Paradis, Herman Tam, Martine Lemire, Donna Martin, Philippe Bégin, Linda Pedder, Jeffrey S. Zaltzman, Timothy Teoh, Greg J. Evans, Preeti Zimmer, Lucy Chen, Christopher Mill, Kateryna Vostretsova, Scott J. Tebbutt, Casey P. Shannon, Gillian Bartlett, Nikita Raje, Evelyn Gunawan, Bruce Mazer, Kevin E. Renahan, Stephane Barakat, Charles S. Barnes, Sudhir Gupta, Salaheddin M. Mahmud, Elli Rosenberg, Alexander Ho, Michael Trus, Meghan B. Azad, Harley Eisman, Ricardo Jimenez, Savannah Grodecki, Jean-Phillipe Drolet, Christelle Bourgeois, Lisa W. Fu, Gail M. Gauvreau, Cristina Longo, Shiyuan Zhang, Andrea E. Burke, Frank Albers, Heinz Leibl, Victoria E. Cook, Christopher Carlsten, Elinor Simons, Jenny Thiele, Amber Oberle, Padmaja Subbarao, Matthew C. Tunis, Ahmed A. Darwish Hassan, R. Robert Schellenberg, Alexander Singer, Jennifer A. Sullivan, Paul K. Keith, Isaac Melamed, Meredith D. Chiasson, Andrew Moses, Amin Kanani, Bassel Dawod, Danay Maestre-Batlle, Diana L. Lefebvre, Rishma Chooniedass, Jeffrey R. Brook, Gina Lacuesta, Adelle Atkinson, Lorena Vehling, Sofianne Gabrielli, Tracie A. Barnett, Judy Morris, Iftikhar Hussain, Tibor Schuster, Edson Castilho, Edmond S. Chan, Colin Barber, Mihaela Paina, Brooke I. Polk, Amrit Singh, Keely Loewen, Brenda MacGibbon, Lisa M. Steacy, Michelle L. North, Yasmin Othman, Gordon L. Sussman, Elodie Portales-Casamar, Yahya Fiteih, Joel Liem, Diana Quint, Sandor Fritsch, Yann Amistani, Hanan Alshamali, Kenneth Paris, Francisco J.D. Noya, Vanessa Omana, Jacques Hébert, Harissios Vliagoftis, Vishal Avinashi, Moshe Ben-Shoshan, Olga M. Pena, Lori A. Connors, Annika Klopp, Andrew Wakeman, Desmond Leddin, François Graham, Ori Scott, Lori Connors, Amanda Ciccolini, Hans Pasterkamp, Eyal Grunebaum, Stephen Couban, Sebastien LaVieille, Geert W. ‘t Jong, Claire Tacon, Kavisha Jayasundara, Anne K. Ellis, S.E. Turvey, Beverley Temple, Fernando Aleman, Jean S. Marshall, Malcolm R. Sears, Peter Menikefs, Kevin Woodward, Roberta L. Woodgate, Piushkumar J. Mandhane, Martin Noel, Marianne Beland, Necdet B Gunsoy, John-Paul Oliveria, Saiful Huq, Adrienne Roos, Josiane Cognet-Sicé, Lawrence Joseph, Mark Larché, Anne Des Roches, Katia Charland, Michelle Bolner, Anette Kocbach Bølling, Gordon Sussman, Teresa Pun, Olivier Chambenoi, Nikhil Joshi, Mark FitzGerald, Francine M. Ducharme, M.R. Sears, Vy Hong-Diep Kim, Raphael Hanna, Leah T. Stiemsma, Piushkumar Mandhane, Brad Millson, Donald Stark, Persia Pourshahnazari, Laurie Lee, Mohammad A. Alsayegh, Joseph Shuster, Hani Hadi, Thomas B. Issekutz, Anna Cvetkovic, Barret A. Monchka, Christos M. Tsoukas, Jonathan Lacombe-Barrios, Douglas P. Mack, Elizabeth A. Lee, Susan Waserman, Sebastien K. Gerega, Scott Sawyer, Parameswaran Nair, Shairaz Baksh, Miriam Diamond, Judah A. Denburg, Wade Watson, Ann E. Clarke, Christopher F. Rider, Christopher Mills, Kara Robertson, Jay M. Portnoy, Sima Chiva-Razavi, Lindsay Douglas, Kathy Abiteboul, Damian Tworek, Babar Haroon, F. Estelle R. Simons, Hana Müllerová, Pascale Dupuis, Sara F. Johnson, Gilbert Nadeau, William Powley, Lana Rosenfield, Stuart E. Turvey, Reza Alizadehfar, Greg Plunkett, Steven G. Smith, Chris Olesovsky, Christine McCusker, and Mousa Khadada

Subjects
Allergic Rhinitis, lcsh:Immunologic diseases. Allergy, Allergy, medicine.medical_specialty, Clinical immunology, business.industry, Alternative medicine, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, Meeting Abstracts, Food Allergy, Chronic Granulomatous Disease, Asthma, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Family medicine, Immunology, Medicine, lcsh:RC581-607, business
Published
2017
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