Lawrence J. MacPherson
Novartis
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Featured researches published by Lawrence J. MacPherson.
Inflammation Research | 1995
E. M. O'Byrne; David Thomas Parker; E. D. Roberts; Ronald L. Goldberg; Lawrence J. MacPherson; V. Blancuzzi; D. Wilson; H. N. Singh; R. Ludewig; Vishwas Ganu
Matrix metalloproteinases (MMP) are elevated in human osteoarthritic cartilage [1] and in cartilage from rabbits with experimental osteoarthritis (OA) following partial meniscectomy [2]. CGS 27023A is a M M P inhibitor that inhibits stromelysin, collagenase and gelatinase. CGS 27023A is an orally active inhibitor of stromelysin. CGS 27023A at 75 gmoles/kg p.o. inhibits release of proteoglycan into synovial fluid following intra-articular injection of stromelysin into rabbit knees. The purpose of these experiments was to determine whether CGS 27023A would inhibit cartilage proteoglycan loss in a partial meniscectomy model of osteoarthritis in rabbits [3]. Doxycycline was used as a reference drug [4].
Inflammation Research | 1995
Ronald L. Goldberg; David Thomas Parker; Lawrence J. MacPherson; Vishwas Ganu; Richard Melton; Shou-Ih Hu; V. Blancuzzi; D. Wilson; J. R. Doughty; S. Spirito; E. M. O'Byrne
Mat r ix me ta l lopro teases ( M M P s ) such as s t romelysin , col lagenase and gela t inase are e levated in the synovial fluids o f pa t ien ts wi th arthri t is . The ext racel lu lar ma t r ix o f car t i lage is suscept ible to deg rada t ion by these proteases . A desi rable p r o p e r t y o f a ma t r ix me ta l lop ro tease inh ib i to r ( M M P I s ) is one tha t inhibi ts ma t r ix me ta l lopro teases f rom degrad ing car t i lage in the joint . W e repor t here our f indings of a mode l tha t tests the d u r a t i o n o f ac t ion and oral b ioava i lab i l i ty o f M M P I s to inhibi t M M P s in the synovia l fluid.
Archive | 1999
Elizabeth O’Byrne; V. Blancuzzi; Hem Singh; Lawrence J. MacPherson; David Thomas Parker; E. Donald Roberts
Breakdown of articular cartilage is a primary feature of osteoarthritis (OA) that leads to loss of joint function. Cartilage degradation involves a progressive loss of proteoglycan matrix and chondrocytes, surface fraying, and erosion. Matrix metalloproteases (MMPs) have been implicated in the destruction of cartilage in OA. CGS 27023A is an orally active inhibitor of stromelysin (MMP-3) and collagenase (MMP-1). CGS 27023A was used to evaluate the effects of an MMP inhibitor on the development of cartilage pathology in a surgical model of OA in rabbits and naturally occurring OA in guinea pigs. Focal OA lesions were produced in rabbits by partial lateral meniscectomy (MNX). Rabbits given CGS 27023A at 100mg/kg in food for 8 weeks following MNX had a lower mean score for cartilage pathology (P <.005) than controls. Spontaneous OA occurs naturally in the knees of guinea pigs, starting during the first 6 months of age and progressing during the next year. By 12 months of age, articular cartilage degeneration including loss of proteoglycan and chondrocytes and surface fibrillation were observed in the medial tibia of the majority of untreated guinea pigs. Guinea pigs administered CGS 27023A in food from 6 months to 12 months of age had reduced histology scores for cartilage lesions (P <.05). These observations support the hypothesis that an MMP inhibitor would ameliorate cartilage destruction by protecting the collagen framework and proteoglycan matrix in OA patients.
Archive | 1993
Lawrence J. MacPherson; David Thomas Parker
Journal of Medicinal Chemistry | 1997
Lawrence J. MacPherson; Erol K. Bayburt; Michael Paul Capparelli; Brian J. Carroll; Robert Goldstein; Michael R. Justice; Lijuan Zhu; Shou-Ih Hu; Richard Melton; Lynn Fryer; Ronald L. Goldberg; J. R. Doughty; Salvatore Spirito; V. Blancuzzi; Doug Wilson; E. M. O'Byrne; Vishwas Ganu; David Thomas Parker
Archive | 1995
Lawrence J. MacPherson; David Thomas Parker; Arco Y. Jeng
Archive | 1994
Lawrence J. MacPherson; David Thomas Parker; Arco Y. Jeng
Archive | 1997
Philippe Nantermet; David Thomas Parker; Lawrence J. MacPherson
Journal of Medicinal Chemistry | 1993
Lawrence J. MacPherson; Erol K. Bayburt; Michael Paul Capparelli; Regine Bohacek; Frank H. Clarke; Rajendra D. Ghai; Yumi Sakane; Carol Berry; Jane V. Peppard; Angelo J. Trapani
Archive | 1996
Lawrence J. MacPherson; David Thomas Parker