Human Apyrase Therapy for Diabetic Neuropathic Pain

DESCRIPTION provided by applicant Neuropathic pain such as diabetic neuropathic pain DNP can be difficult to treat with only of patients achieving meaningful andgt pain relief Current therapies e g duloxeline mainly address symptoms by focusing on blocking neurotransmission in the pain pathway with limited efficacy potentially severe side effects and narrow therapeutic index Hence novel therapies are needed to safely manage symptoms and also target the underlying pathophysiological mechanisms that will improve the functional status and life quality of affected patients APT an optimized human apyrase selectively scavenges excess pro inflammatory and algogenic extracellular ATP eATP and ADP eADP and metabolizes them to eAMP thereby attenuating vascular or central inflammation and pain Ubiquitous CD further metabolizes eAMP to adenosine which has been shown to reduce neuropathic pain in animals and humans It has been shown that administration of APT exhibited a long lasting days anti hyperalgesic effect in the model of Complete Freudandapos s Adjuvant induced inflammatory pain with no noticeable side effects In the proposed studies we will evaluate the dose response of APT in both the chronic constriction injury CCI model of neuropathy and the model of STZ induced diabetic neuropathy We also will determine the potential side effects of APT using the rotarod and functional observational battery assays in healthy rats Specific Aim To determine whether APT s c will abrogate neuropathic pain in the CCI model in rats without behavioral side effects Specific Aim To determine whether APT s c will abrogate neuropathic pain in the STZ induced diabetic model in rats without significant side effects The long term goal is to develop APT as a safe and disease modifying analgesic therapy Weekly or monthly dosing will provide sustained pain relief for neuropathic pain patients without significant side effects tolerance or addiction PUBLIC HEALTH RELEVANCE We will determine whether an optimized human apyrase will abrogate diabetic neuropathic pain without behavioral side effects in animal models