Figures & data
Figure 1 NGF signaling pathways in mediating neurotrophic and nociceptor effects.
Notes: NGF signals through the high-affinity TrkA and low p75NTR receptors. TrkA activates both PI3 kinase (PI3K) and Ras pathways, which lead to cell survival and neurite outgrowth. Signaling through p75NTR leads to apoptosis, which is blocked by the TrkA-activated PI3K pathway. PI3K activation also leads to activation of the nonselective cation channel TRPV1 by phosphorylation, thereby generating action potential for nociceptive functions. Moreover, TRPV1 phosphorylation results in increased translocation of TRPV1 to the plasma membrane to enhance channel activity. Antibody-mediated NGF blockade results in the abolition of both neurotrophic and nociceptor functions.
Abbreviation: NGF, nerve growth factor.
Abbreviation: NGF, nerve growth factor.
Figure 2 Proposed study schema to assess NGF-dependence of tanezumab efficacy. (A) Proof-of-concept study in which NGF is measured in EPS and urine before and after treatment with placebo or tanezumab at two different doses. (B) Pivotal study in which NGF levels are measured at pre- and posttreatment time points to establish NGF levels as a predictive biomarker for anti-NGF therapy.
Abbreviations: EPS, expressed prostatic secretion; NGF, nerve growth factor.
