ABSTRACT
Chronic neuropathic pain, which is one of the most common forms of chronic pain, is a highly prevalent condition
that dramatically decreases productivity and quality of life; it is often associated with insomnia, anxiety and
depression, and does not respond well to existing treatments with >50% of patients who are refractory to current
medications. Additionally, many pain relief medications are highly addictive, and may involve numerous issues
with withdrawal and risks of overdosing. In 2017, more than 47,000 Americans died from an opioid overdose,
according to the Centers for Disease Control and Prevention, causing a National Emergency. Thus, there is an
urgent need to develop non-opioid analgesics to treat chronic neuropathic pain.
To date, attempts at developing novel analgesics have been and continue to be hindered by high clinical attrition
and cross-species translational difficulties, resulting in lack of efficacy in pivotal Phase II clinical studies. A very
promising avenue for advancing pain research is provided by the recently-established possibility of performing
of studies directly on human sensory neurons. Functional, electrophysiology-based studies of human nociceptive
neurons are now possible, allowing the direct phenotypic screening and drug candidate profiling in human tissue-
based assays at the preclinical stage. This approach has the potential to overcome many of the limitations
associated with cross-species differences encountered when using animal models of pain for the identification
and selection of clinical drug candidates.
AnaBios has developed a novel translational drug screening platform for the generation of human-relevant data
in preclinical pain drug discovery. Over the past 9 years, we have developed methods that enable the recovery
and interrogation of hDRG; these technologies allow for studies aimed at advancing knowledge of basic pain
biology as well as supporting drug discovery efforts. For preclinical-stage drug development programs it is critical
to assess: 1) the potential of a new drug candidate in human-relevant models; 2) the activity in specific pain
states; 3) the potency. Our proposal aims at introducing new in vitro models to enable the assessment of potential
analgesic activity, directly on human samples, at early preclinical stages. Specifically, the development and
qualification of in vitro models of pathological states associated with pain is a central goal of the proposal.
The availability of qualified pathological models will provide a highly valuable tools for advancing the
development of new non-addictive drugs for the treatment of pain. The utilization of primary human cells in
translational research and drug discovery can provide data that are essential for addressing two critical
translational challenges: the selection of the dose for first-in-human studies and, the selection of the appropriate
patient population for proof of concept pivotal Phase 2 clinical studies. This proposal will advance the
development of our novel screening platform and will ultimately help bypass the cross-species translational
hurdles which have impeded the progress of pain drug development for decades.
