Proof of Concept Trial of Tanezumab for the Treatment of Symptoms Associated With Interstitial Cystitis

Evans, Robert J.; Moldwin, Robert; Cossons, Nandini; Darekar, Amanda; Mills, Ian W.; Scholfield, David

doi:10.1016/j.juro.2010.12.088

Cited by 142 publications

(96 citation statements)

References 20 publications

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“…206 Intravenous tanezumab, an anti-nerve growth factor, demonstrated a statistically significant decrease in daily pain score and improvement in global response assessment in a Phase 2 RCT. 207 A meta-analysis of all female patients diagnosed with urologic CPPS showed a significant benefit with tanezumab treatment compared to placebo. Guideline: Monoclonal antibodies are not available or recommended for IC/BPS at this point, but further studies are needed.…”

Section: Monoclonal Antibodies Against Tnf-alphamentioning

confidence: 99%

CUA guideline: Diagnosis and treatment of interstitial cystitis/ bladder pain syndrome

Cox

Golda

Nadeau

et al. 2016

CUAJ

115

121

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MethodologyThe following guidelines were based on MEDLINE and PUBMED searches of English language literature, in addition to consensus conference proceedings. Levels of evidence and grades of recommendation were assigned for each investigation and treatment, as per the modified Oxford Centre for Evidence-Based Medicine grading system. Where the literature was inconsistent or scarce, a consensus expert opinion was generated to provide treatment guidelines.

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Section: Monoclonal Antibodies Against Tnf-alphamentioning

confidence: 99%

CUA guideline: Diagnosis and treatment of interstitial cystitis/ bladder pain syndrome

Cox

Golda

Nadeau

et al. 2016

CUAJ

115

121

View full text Add to dashboard Cite

show abstract

“…For instance, with the clarification of the role NGF plays in chronic inflammatory pain, researchers evaluated the efficacy of anti-NGF therapy in chronic pain associated with osteoarthritis (Sanga et al, 2013;Tiseo et al, 2014), interstitial cystitis (Evans et al, 2011), diabetic neuropathy (Bramson et al, 2015), chronic pelvic pain syndrome (Nickel et al, 2012), and chronic low back pain (Gimbel et al, 2014), and the results were optimistic. Given that chronic abdominal pain is one of the main manifestations of IBS-D, it is worth further investigation as to whether anti-NGF therapy could show similar optimistic results in IBS-related abdominal pain, as well as other symptoms.…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?

Liu

Yao

2016

J. Zhejiang Univ. Sci. B

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Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort associated with abnormal bowel habits. Diarrhea-predominant IBS (IBS-D) is a major subtype of IBS, the predominant manifestations of which are abdominal pain and diarrhea. The pathogenesis of IBS-D remained unknown until recently. The effects of psychosocial stress, central hypervigilance, neuroendocrine abnormality, disturbed gastrointestinal motility, mucosal immune activation, intestinal barrier dysfunction, visceral hypersensitivity (VH), altered gut flora, and genetic susceptibility may be involved in its development. Recently, increased attention has been placed on the neural-immune-endocrine network mechanism in IBS-D, especially the role of various neuroendocrine mediators. As a member of the neurotrophin family, nerve growth factor (NGF) has diverse biological effects, and participates in the pathogenesis of many diseases. Basic studies have demonstrated that NGF is associated with inflammatory-and stress-related VH, as well as stress-related intestinal barrier dysfunction. The aim of this study is to summarize recent literature and discuss the role of NGF in the pathophysiology of IBS-D, especially in VH and intestinal barrier dysfunction, as well as its potential as a therapeutic target in IBS-D.

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“…In the last 20 years the link between the biology of nerve growth factor (NGF) and pain has been well established Pezet and McMahon, 2006;Mantyh et al, 2011). At present, there are at least five major pharmaceutical companies running clinical trials of humanized antibodies designed to sequester NGF for the treatment of pain in conditions as varied as osteoarthritis, lower back pain and interstitial cystitis (Cattaneo, 2010;Lane et al, 2010;Evans et al, 2011;Brown et al, 2012Brown et al, , 2013. The first example of an NGF sequestering drug is Tanezumab a humanized monoclonal antibody that potently binds NGF developed by Rinat/Pfizer (Lane et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

Lewin

Lechner

Smith

2014

Handbook of Experimental Pharmacology

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Nerve growth factor (NGF) is central to the development and functional regulation of sensory neurons that signal the first events that lead to pain. These sensory neurons, called nociceptors, require NGF in the early embryo to survive and also for their functional maturation. The long road from the discovery of NGF and its roles during development to the realization that NGF plays a major role in the pathophysiology of inflammatory pain will be reviewed. In particular, we will discuss the various signaling events initiated by NGF that lead to long lasting thermal and mechanical hyperalgesia in animals and in man. It has been realized relatively recently that humanized, function blocking antibodies directed against NGF show remarkably analgesic potency in human clinical trials for painful conditions as varied as osteoarthritis, lower back pain and interstitial cystitis. Thus, anti-NGF medication has the potential to make a major impact on day-to-day pain treatment in the near future. It is therefore all the more important to understand the precise pathways and mechanisms that are controlled by NGF to initiate and sustain mechanical and thermal hyperalgesia. Recent work suggests that NGF-dependent regulation of the mechanosensory properties of sensory neurons that signal mechanical pain may open new mechanistic avenues to refine and exploit relevant molecular targets for novel analgesics.

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Proof of Concept Trial of Tanezumab for the Treatment of Symptoms Associated With Interstitial Cystitis

Abstract: Tanezumab has shown preliminary efficacy in the treatment of pain associated with interstitial cystitis.

Cited by 142 publications

References 20 publications

CUA guideline: Diagnosis and treatment of interstitial cystitis/ bladder pain syndrome

CUA guideline: Diagnosis and treatment of interstitial cystitis/ bladder pain syndrome

Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

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