Table 3.
NGF blockade in experimental models of osteoarthritis
| Type of study | OA Model | Drug | Results | Reference |
|---|---|---|---|---|
| Therapeutic: One time injection | Destabilization of the medial meniscus (DMM); mouse | TrkA inhibitor (TrkAD5; 2 mg/kg, s.c.) | Reversed weight-bearing asymmetry for 3 days when given at the 16-week time point | McNamee 2010 |
| Therapeutic: One time injection | Monosodium iodoacetate (MIA); rat | anti- NGF (AS2886401–00; 0.3 or 1 mg/kg, i.v.) | Anti-NGF (0.3 or 1 mg/kg) given on day 3 or day 28 was able to suppress gait imbalances. Anti-NGF given on day 3 exacerbated knee swelling by day 35 of the model. | Ishikawa 2015 |
| Therapeutic: One time injection | Bilateral MIA; rat | anti-NGF (extracted from the patent application WO 2004/058184 A2; 9 mg/kg, s.c.) | Anti-NGF given on day 2 after MIA induction reversed burrowing deficits 24 hours later | Bryden 2015 |
| Therapeutic: One time injection | MIA; rat | anti-NGF (L148M (Exalpha Biological Inc.); 10mg/kg, i.p.) | Anti-NGF therapy given on day 21 inhibited gait changes for one week | Miyagi 2017 |
| Preventative or Therapeutic | MIA; rat | anti-NGF (muMab911; 10 mg/kg; s.c. weekly) |
Preventative (from day 0): Prevented development of weight-bearing asymmetry. Mechanical allodynia of the hind paw was reduced on day 28 only. There was a trend in increased cartilage damage score with treatment. Therapeutic (injections on days 14 and 21): Reversed weight-bearing asymmetry and hind paw mechanical allodynia through day 28. No change in cartilage damage score. |
Xu 2016 |
| Preventative or Therapeutic | Meniscal transection (MNX); rat | TrkA inhibitor (AR786; 30 mg/kg, orally, twice daily) |
Preventative (from 1 h before surgery): Prevented development of weight-bearing asymmetry and hind paw mechanical allodynia. Preventative (from 1 h before surgery – day 14): Withdrawal of treatment on day 14 continued to provide relief in weight-bearing asymmetry until day 24, but hind paw mechanical allodynia developed rapidly when treatment stopped and was fully developed by day 19. Therapeutic (day 14–21): Weight-bearing asymmetry and hind paw mechanical allodynia reduced after 5 days of treatment. |
Nwosu 2016 |
| Therapeutic | MIA; rat | Therapeutic (day 14–21): Weight-bearing asymmetry reduced after 3 days of treatment. Hind paw mechanical allodynia reduced after 5 days of treatment. Synovitis and cartilage degeneration were reduced with treatment. | ||
| Preventative or Therapeutic | Medial meniscal tear (MMT); rat | anti-NGF (tanezumab; 0.1, 1 or 10 mg/kg; s.c. once a week) |
Preventative (from day 0): All doses decreased gait changes observed at day 3 post surgery, but all doses increased cartilage damage scores in rats taken down at day 7, 14, or 28. Therapeutic (0.1 mg/kg, day 23–37): Cartilage damage score increased with treatment. Therapeutic (0.1 mg/kg, day 57–71): Cartilage damage score increased with treatment, but not significantly since damage was already severe by the time treatment was started. |
LaBranche 2017 |
| Preventative or Therapeutic | Male partial medial meniscectomy (PMX); mouse | anti-NGF vaccination |
Preventative (first immunization 2 weeks prior to surgery): Immunization with 3 boosters reduced weight-bearing asymmetry. No change in cartilage damage score. Therapeutic (first immunization week 10 after surgery): Immunization with 2 boosters reduced weight-bearing asymmetry until antibody titers decreased. |
von Loga 2019 |
| Therapeutic | Mechanical loading; mouse | anti-NGF (MedImmune, AstraZeneca; 3 mg/kg; i.p. every two weeks) | Therapeutic (week 2 and 4 post loading): Each anti-NGF injection reduced hind paw mechanical allodynia for 6 days until the allodynia began to return. Similarly, anti-NGF reduced weight bearing asymmetry for 1 week post injection but returned by week 2. | Ter Heegde 2019 |