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904 results on '"Hood J"'

4. A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee

Author

Deshmukh, V, Hu, H, Barroga, C, Bossard, C, KC, S, Dellamary, L, Stewart, J, Chiu, K, Ibanez, M, Pedraza, M, Seo, T, Do, L, Cho, S, Cahiwat, J, Tam, B, Tambiah, JRS, Hood, J, Lane, NE, and Yazici, Y

Subjects
Biomedical and Clinical Sciences, Health Sciences, Clinical Sciences, Sports Science and Exercise, Stem Cell Research - Nonembryonic - Human, Arthritis, Osteoarthritis, Regenerative Medicine, Aging, Biotechnology, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Musculoskeletal, Animals, Anti-Inflammatory Agents, Cartilage, Articular, Cell Differentiation, Cells, Cultured, Chondrocytes, Dimethyl Sulfoxide, Imidazoles, Indazoles, Male, Osteoarthritis, Knee, Pyridines, Rats, Sprague-Dawley, Regeneration, Solvents, Wnt Signaling Pathway, Wnt signaling, Chondrocyte, ACLT, DMOAD, Small molecule, Biomedical Engineering, Human Movement and Sports Sciences, Arthritis & Rheumatology, Clinical sciences, Sports science and exercise
Abstract

ObjectivesOsteoarthritis (OA) is a degenerative disease characterized by loss of cartilage and increased subchondral bone within synovial joints. Wnt signaling affects the pathogenesis of OA as this pathway modulates both the differentiation of osteoblasts and chondrocytes, and production of catabolic proteases. A novel small-molecule Wnt pathway inhibitor, SM04690, was evaluated in a series of in vitro and in vivo animal studies to determine its effects on chondrogenesis, cartilage protection and synovial-lined joint pathology.DesignA high-throughput screen was performed using a cell-based reporter assay for Wnt pathway activity to develop a small molecule designated SM04690. Its properties were evaluated in bone-marrow-derived human mesenchymal stem cells (hMSCs) to assess chondrocyte differentiation and effects on cartilage catabolism by immunocytochemistry and gene expression, and glycosaminoglycan breakdown. In vivo effects of SM04690 on Wnt signaling, cartilage regeneration and protection were measured using biochemical and histopathological techniques in a rodent acute cruciate ligament tear and partial medial meniscectomy (ACLT + pMMx) OA model.ResultsSM04690 induced hMSC differentiation into mature, functional chondrocytes and decreased cartilage catabolic marker levels compared to vehicle. A single SM04690 intra-articular (IA) injection was efficacious in a rodent OA model, with increased cartilage thickness, evidence for cartilage regeneration, and protection from cartilage catabolism observed, resulting in significantly improved Osteoarthritis Research Society International (OARSI) histology scores and biomarkers, compared to vehicle.ConclusionsSM04690 induced chondrogenesis and appeared to inhibit joint destruction in a rat OA model, and is a candidate for a potential disease modifying therapy for OA.

Published
2018

5. A novel Wnt pathway inhibitor, SM04690, for the treatment of moderate to severe osteoarthritis of the knee: results of a 24-week, randomized, controlled, phase 1 study

Author

Yazici, Y, McAlindon, TE, Fleischmann, R, Gibofsky, A, Lane, NE, Kivitz, AJ, Skrepnik, N, Armas, E, Swearingen, CJ, DiFrancesco, A, Tambiah, JRS, Hood, J, and Hochberg, MC

Subjects
Pain Research, Chronic Pain, Clinical Research, Aging, Osteoarthritis, Clinical Trials and Supportive Activities, Arthritis, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Musculoskeletal, Aged, Antirheumatic Agents, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Imidazoles, Indazoles, Injections, Intra-Articular, Male, Middle Aged, Osteoarthritis, Knee, Pain Measurement, Pyridines, Radiography, Severity of Illness Index, Wnt Signaling Pathway, DMOAD, Small molecule, Wnt pathway, Biomedical Engineering, Clinical Sciences, Human Movement and Sports Sciences, Arthritis & Rheumatology
Abstract

ObjectiveTo assess the safety, pharmacokinetics, and exploratory efficacy of SM04690, a novel Wnt pathway inhibitor, as a potential disease modifying treatment for knee osteoarthritis (OA).DesignSubjects with Kellgren-Lawrence grade 2-3 knee OA were randomized in successive dose-escalation cohorts to receive a knee intra-articular (IA) injection with 0.03, 0.07, or 0.23 mg SM04690, or placebo (PBO) (4:1 ratio). Safety, pharmacokinetics, efficacy (WOMAC Total/Function/Pain, Pain VAS, Physician Global Assessment [MDGA], and OMERACT-OARSI Response), OA-related biomarker (P1NP, ß-CTX, and cartilage oligomeric matrix protein [COMP]), and radiographic/imaging data were collected at baseline and during 24-week follow-up.Results61 subjects (SM04690 n = 50; PBO n = 11) enrolled. Two dose limiting toxicities (DLTs), increased pain following injection and paroxysmal tachycardia (also the single serious AE), were reported in the 0.07 mg cohort. A total of 72 AEs were reported; Sixteen (occurring in eight subjects) were considered related to study medication. There were three discontinuations; one due to an AE (0.03 mg cohort). Bone marrow edema (BME) remained constant for most subjects. No doses were excluded from further study due to DLT criteria. Plasma levels of SM04690 were below the limit of detection at all time points. At Week 24, improvements from baseline were seen in all cohorts for the exploratory measures WOMAC Total, WOMAC Function, WOMAC Pain, MDGA, Pain VAS, and OMERACT-OARSI response. Joint space width (JSW) improvement was observed in the 0.07 mg cohort (P = 0.02 vs PBO).ConclusionSM04690 appeared safe and well tolerated, with no evidence of systemic exposure. Exploratory efficacy analyses suggested positive trends for measurements of OA pain, function and disease-modifying osteoarthritis drug (DMOAD) properties. CLINICALTRIALS.Gov registrationNCT02095548.

Published
2017

7. Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment

Author

Deshmukh, V., O'Green, A.L., Bossard, C., Seo, T., Lamangan, L., Ibanez, M., Ghias, A., Lai, C., Do, L., Cho, S., Cahiwat, J., Chiu, K., Pedraza, M., Anderson, S., Harris, R., Dellamary, L., KC, S., Barroga, C., Melchior, B., Tam, B., Kennedy, S., Tambiah, J., Hood, J., and Yazici, Y.

Published
2019
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11. In the News

Author

Salvail, J.Z., Wright, G. A., Kleinewietfeld, M., Wu, C., Yosef, N., Hood, J. L., Jallouk, A. P., Campbell, N., Ratner, L., Wickline, S. A., and Luis, A. D.

Published
2013

26. Central Venous Catheters and Infection

Author

Curran, E. T., Booth, M., Hood, J., Cooke, R. P. D., Watson, N. A., Myerson, K., Umasankar, R. S., Cook, J., Bernau, Frances, Dexter, T. J., Elliott, Tom, and Faroqui, Muzaffar

Published
1998

40. Irish cardiac society Proceedings of Annual General Meeting held 4th/5th November, 1994

Author

Oslizlok, P., Duff, D., Denham, B., Penny, W. J., Banning, A. P., Groves, P. H., Brewer, L., Lewis, M. J., Cheadle, H., Crawford, N., Kearney, P. P., Starkey, I. R., Fort, S., McMurray, J. V., Shaw, T. R., Sutherland, G. R., Hennessy, T., McCann, H., Sugrue, D., Foley, D. P., Melkert, R., Keane, D., Serruys, P. W., Vaughan, C. J., O’Connell, D. P., McDonald, D., Blake, S., Garadah, T., Mehana, N., King, G., Gearty, G., Crean, P., Walsh, M., Galvin, J., Codd, M. B., McCann, H. A., Sugrue, D. D., Gaylani, N. El, Weston, C., Thomas, A., Davies, L., Tovey, J., Musumeci, F., Singh, H. P., Hargrove, M., Fennell, W., Aherne, T., Crowley, J. J., Hassanein, H., Shapiro, L. M., McCrissican, D., Morton, P., O’Donnell, A. F., McBrinn, S., McCarthy, J., McCarthy, D., Neligan, M. C., McGovern, E., Herity, N. A., Allen, J. D., Silke, B., Adgey, A. A. J., Johnston, P. W., Anderson, J., McIlroy, R. L., Dunn, H. M., Nikookam, K., McNeill, A. J., Foley, P., Foley, D., de Jaegere, P., Serruys, P., O’Callaghan, D., Vela, J., Maguire, M., Horgan, J., Graham, A. N. J., Wilson, C. M., Hood, J. M., D’SA, A. A. B. Barros, Khan, M. M., McClements, B., Dalzell, G., Campbell, N. P. S., Webb, S. W., Shandall, A., Buchalter, M. B., Northbridge, D. B., McMurray, J., Dargie, H. J., Sullivan, P. A., McLoughlin, M., Varma, M. P. S., Charleton, P., Turkington, E., Rusk, R. A., Richardson, S. G., Hale, A., O’Shea, J. C., Murphy, M. B., Diamond, P., McAleer, B., Davies, S., Kinnaird, T., Duly, E., McKenna, C. J., Codd, M., McGee, H. M., Browne, C., Horgan, J. H., and The Council on Acute Coronary Care of the Irish Heart Foundation

Published
1995
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43. Irish society of gastroenterology: Proceedings of meeting held in university college, Galway in may 1892

Author

Brannigan, A., Williams, N. N., Grahn, M., Williams, N. S., Fitzpatrick, J. M., O’Connell, P. R., Soong, C. V., Blair, P., Halliday, M. I., Hood, J. M., Rowlands, B. J., D’sa, A. A. B. Barros, Cahill, R. J., Beattie, S., Hamilton, H., O’Morain, C., Kelly, S. J., O’Malley, K. E., Stack, W. A., O’Donoghue, D., Baird, A. W., Cronin, K. J., Kerin, M. J., Crowe, J., MacMathuna, P., Lennon, J., Gorey, T. F., Chua, A., O’Kane, V., Dinan, T. G., Keeling, P. W. N., Mulligan, E., Cronin, K. L., Dervan, P., Ireland, A., Murphy, D., O’Sullivan, G., Ryan, E., Kelly, P., Gilvarry, J., Sant, S., Fan, X. J., Chua, A., Shahi, C. N., O’Connell, M., Weir, D. G., Kelleher, D., McDevitt, J., O’Donoghue, J. M., Horgan, P. G., Byrne, W. J., McGuire, M., Given, H. F., Daw, M. A., Kavanagh, P., O’Mahony, P., Joy, T., Gleeson, F., Mullan, A., Gibney, M., Mannion, Anne, Stevens, F. M., McCarthy, C. F., Killeen, A. A., Murchan, P. M., Reynolds, J. V., Leonard, N., Marks, P., Keane, F. B. V., Tanner, W. A., O’Connell, M. A., Corridan, B., Collins, R., Shannon, R., Cahill, R., Joyce, W. P., Goggin, M., O’Donoghue, D., Hyland, J., Traynor, O., Qureshi, A., DaCosta, M., Brindley, N., Burke, P., Grace, P., Bouchier-Hayes, D., Leahy, A. L., Courtney, G., Osbome, H., O’Donovan, N., O’Donoghue, M., Collins, J. K., Morrissey, D., McCarthy, J. E., Redmond, H. P., Hill, A. D. K., Grace, P. A., Naama, H., Austin, O. M., Bouchier-Hayes, D. M., Daly, J. M., Mulligan, E., Fitzpatrick, J. M., Breslin, D., Delaney, C. P., O’Sullivan, S. T., O’Sullivan, G. C., Kirwan, W. O., Weir, C. D., McGrath, L. T., Maynard, S., Anderson, N. H., Halliday, M. I., D’sa, A. A. B. Barros, Gokulan, C., O’Gorman, T. A., Breshihan, E., Lam, Pin Yin, Skehill, R., Grimes, H., McKeever, J. A., Stokes, M. A., Mehigan, D., Keaveny, T. V., Meehan, J., Molloy, A., Q’Farrelly, C., Scott, J., Dudeney, M. S., Leahy, A., Grace., P. A., McEntee, G., Hcaton, N. D., Douglas, V., Mondragon, R., O’Grady, J., Williams, R., Tan, K. C., Xia, H. X., Keane, C. T., O’Morain, C. A., O’Mahony, A., O’Sullivan, G. C., Corbett, A., O’Mahony, A., Ireland, A., Harte, P., Mulcahy, H., Patchett, S., Stack, W., Gallagher, M., Connolly, K., Doyle, J., Flynn, J. R., Maher, M., Hehir, D., Horgan, A., Stuart, R., Brady, M. P., Johnston, P. W., Johnston, B. T., Collins, B. J., Collins, J. S. A., Love, A. H. G., Marshall, S. G., Parks, T. G., Spence, R. A. J., O’Connor, H. J., Cunnane, K., Duggan, M., MacMalhuna, P., Delaney, C. P., Kerin, M., Gorey, T. F., Attwood, S. E. A., Viani, L., Jeffers, M., Walsh, T. N., Byrne, P. J., Frazer, I., Hennessy, T. P. J., Hill, G. L., Dickey, W., McMillan, S. A., Bharucha, C., Porter, K. G., Rolfe, H., Thornton, J., Attwood, S. E. A., Coleman, J., Stephens, R. B., Hone, S., Holmes, K., Kelly, I. P., Corrigan, T. P., McCrory, D., McCaigue, M., Barclay, G. R., Stack, W. A., Quirke, M., Hegarty, J. E., O’Donoghue, D. P., O’Hanlon, D., and Byrne, J.

Published
1992
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