G Ishikawa1, Y Koya2, H Tanaka3, Y Nagakura4. 1. Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: go.ishikawa@astellas.com. 2. Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: yukari.koya@astellas.com. 3. Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: hirotsugu.tanaka@astellas.com. 4. Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: yukinori.nagakura@astellas.com.
Abstract
OBJECTIVE: Osteoarthritis (OA) patients experience exaggerated pain during movements such as walking. Anti-nerve growth factor (NGF) antibodies have recently shown analgesic effects in OA patients. We examined the effect of a single dose of anti-NGF antibody on pain during motion, joint edema and lesion in a rat model of OA to determine whether the analgesic effect demonstrated in clinical studies can be translated to a preclinical model. METHODS: Sodium monoiodoacetate (MIA)-induced arthritic rats that develop a right-left gait imbalance when walking as an index of pain during motion. This imbalance was assessed using a gait analysis system called "CatWalk". Edema size and lesion score in the relevant knee joint were also measured. The effect of a single intravenous injection of an anti-NGF monoclonal antibody AS2886401-00 on these parameters was assessed. RESULTS: AS2886401-00 administered at 0.3 or 1 mg/kg on Day 3 post-MIA injection resulted in a statistically significant improvement in gait imbalance even on Day 35. When gait measurement was set on Week 3 post-MIA administration, administration of the antibody at a timing close to the gait measurement, i.e., 1 or 24 h prior to the measurement, was less effective. AS2886401-00 did not suppress either edema or lesion. CONCLUSIONS: A single dose of anti-NGF antibody exerts a long-lasting analgesic effect on pain during motion in a rat model of OA. This finding could be associated with the analgesic efficacies that anti-NGF antibodies have exhibited in clinical studies. It appears unlikely that analgesia is secondary to inhibition of joint edema and lesion.
OBJECTIVE:Osteoarthritis (OA) patients experience exaggerated pain during movements such as walking. Anti-nerve growth factor (NGF) antibodies have recently shown analgesic effects in OA patients. We examined the effect of a single dose of anti-NGF antibody on pain during motion, joint edema and lesion in a rat model of OA to determine whether the analgesic effect demonstrated in clinical studies can be translated to a preclinical model. METHODS:Sodium monoiodoacetate (MIA)-induced arthriticrats that develop a right-left gait imbalance when walking as an index of pain during motion. This imbalance was assessed using a gait analysis system called "CatWalk". Edema size and lesion score in the relevant knee joint were also measured. The effect of a single intravenous injection of an anti-NGF monoclonal antibody AS2886401-00 on these parameters was assessed. RESULTS:AS2886401-00 administered at 0.3 or 1 mg/kg on Day 3 post-MIA injection resulted in a statistically significant improvement in gait imbalance even on Day 35. When gait measurement was set on Week 3 post-MIA administration, administration of the antibody at a timing close to the gait measurement, i.e., 1 or 24 h prior to the measurement, was less effective. AS2886401-00 did not suppress either edema or lesion. CONCLUSIONS: A single dose of anti-NGF antibody exerts a long-lasting analgesic effect on pain during motion in a rat model of OA. This finding could be associated with the analgesic efficacies that anti-NGF antibodies have exhibited in clinical studies. It appears unlikely that analgesia is secondary to inhibition of joint edema and lesion.
Authors: Jaymin Upadhyay; Christian Geber; Richard Hargreaves; Frank Birklein; David Borsook Journal: Neurosci Biobehav Rev Date: 2017-08-12 Impact factor: 8.989