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Pain Management 2016
October 03-04, 2016
Volume 5, Issue 5(Suppl) J Pain Relief
ISSN: 2167-0846 JPAR, an open access journal
conferenceseries .com
October 03-04, 2016 Vancouver, Canada
International Conference on
Pain Research & Management
Susan Macdonald et al., J Pain Relief 2016, 5:5(Suppl)
ADX-102, a novel aldehyde trap, reduces nociceptive behavior in mouse models of carrageenan and
CFA induced pain
Susan Macdonald1, Valerie Cullen1, Todd Brady1, Isaac Levi2, Sigal Meilin2 and Scott Young 1
1Aldeyra Therapeutics, USA
2MD Biosciences Inc., USA
Avariety of aldehyde species have been shown to activate ion channels, such as TRPA1 and TRPV1, involved in mediating
pain. Furthermore, aldehyde dehydrogenase 2 which diminishes aldehyde loads by oxidizing aldehydes to acids has been
shown to modulate acute inflammatory pain in animal models. Thus, aldehyde signaling represents a novel therapeutic target
for the treatment of pain. ADX-102 is a novel small molecule that covalently binds aldehydes including malondialdehyde and
4-hydroxynonenal, which have been shown to mediate inflammatory pain. For that reason, the effect of ADX-102 on acute
inflammatory pain was tested in the carrageenan-induced and Complete Freund’s Adjuvant (CFA)-induced models in mice.
ADX-102 was administered intraperitoneally prior to and after pain induction, at different doses and schedules (30 mg/kg
twice daily [BID], 100 mg/kg once daily [QD], or 100 mg/kg BID). Thermal hypersensitivity, mechanical hypersensitivity
and paw swelling were assessed at various times to explore the effect of modulating aldehyde signaling on different molecular
mechanisms underlying pain. Diclofenac was used as a positive control and vehicle was used as a negative control. ADX-102
mediated dose-dependent reductions in nociceptive behavior in both models of acute pain. In the CFA model, treatment with
100 mg/kg QD or 100 mg/kg BID ADX-102 resulted in statistically significant reductions in thermal hypersensitivity, but
reduced mechanical hypersensitivity only after treatment with 100 mg/kg ADX-102 BID. In the carrageenan model, ADX-102
treatment resulted in statistically significant reductions in thermal hypersensitivity at ADX-102 doses of 30 mg/kg BID and 100
mg/kg BID, but did not affect mechanical hypersensitivity. Minor effects on paw swelling were observed in both models. The
data imply that ADX-102 may differentially affect thermal and mechanical pain pathways. Overall, the results support the role
of aldehyde signaling in pain and suggest that aldehyde traps represent a novel approach for the treatment of pain.
Biography
Susan Macdonald received her PhD from the University of Massachusetts Medical School and did Post-doctoral work at Onyx Pharmaceuticals. She has extensive
experience in Research and Development in the biopharmaceutical industry and is currently Vice President of Research and Development at Aldeyra Therapeutics,
a biotechnology company developing a proprietary family of aldehyde traps, which sequester and allow for the degradation of toxic aldehydes, and thus have broad
therapeutic potential. She has published numerous articles and book chapters.