Meeting translational needs for novel neuropathic pain drug development
Event Details
- Date:
- Thursday, 17 April 2014 - Thursday, 17 April 2014
- Time:
- 11:00 am - 12:00 pm
- Room:
- Rm 219 Sir Lew Edwards Building, St Lucia Campus, UQ
- UQ Location:
- Sir Llew Edwards Building (St Lucia)
- Event category(s):
Event Contact
- Name:
- Mr Lawrence Bremner
- Phone:
- 67374
- Email:
- l.bremner@uq.edu.au
- Org. Unit:
- Medicine
Event Description
- Full Description:
- Abstract
Target validation issues have been a major cause of attrition in Phase 2 efficacy trials, particularly of novel medicines for pain. There have been major advances in understanding the neurobiology and molecular mechanisms underlying pain, yet pain conditions represent a major unmet clinical need. Current treatment for chronic neuropathic pain is least effective, we need to treat around 4 patients before even one patient has 50% pain relief, and these drugs have major side-effects. Clinical trials of new drugs for neuropathic pain have seen a number of high profile failures in recent years, as animal in vivo model results did not predict responses in patients. The reason was not a failure to identify potential pain targets in preclinical studies, but to translate these successfully to chronic pain patients.
We have adopted a translational approach based on clinical validation of novel drug targets in common pain states, using: 1) in vitro human DRG neuron (nociceptor) pain models for pharmacological studies (“clinical trial in a dish”); 2) clinical objective biomarkers and surrogates including skin biopsy, pain evoked cerebral potentials (CHEPS) and functional MRI; and 3) new human volunteer/patient drug target models linked to the drug target mechanism, for validation and use in Phase I / IIa trials (“matchmaking”). The aim was to deliver pre-clinical to POC / Phase II success (and PD in Phase I / IIa) by conducting rational mechanistic trials in homogenous patient cohorts. The selection and assessment of patients with target related biomarkers would better predict clinical outcome.
Our approach has supported target validation and guided the success of 2 novel pain drugs in Phase II trials for chronic neuropathic pain, and one for chronic itch, which will be illustrated: Angiotensin II Type 2 receptor antagonist EMA401 (first discovered by Prof Maree Smith, UQ), p38 MAP kinase inhibitor Dilmapimod, and Trk A inhibitor CT327.
Directions to UQ
- Google Map:
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- Directions:
- St Lucia Campus | Gatton campus.
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