Transaction Description:
MICRODOSING IMPLANT TO MITIGATE DEPRESSION ASSOCIATED WITH OPIOID USE DISORDER - PROJECT SUMMARY/ABSTRACT THE OPIOID EPIDEMIC IS ONE OF THE MAJOR CRISES OF OUR TIME, CAUSING OVER 80,000 OPIOID-RELATED OVERDOSE DEATHS PER YEAR IN THE UNITED STATES AND LEVYING MASSIVE ECONOMIC BURDEN ON OUR HEALTHCARE SYSTEM. MORE THAN HALF OF THE ~2 MILLION INDIVIDUALS SUFFERING FROM OUD HAVE CO-OCCURRING MENTAL ILLNESS, AND IT IS WELL-ESTABLISHED THAT DEPRESSION DURING WITHDRAWAL IS A MAJOR CAUSE OF RELAPSE. THEREFORE, THERAPEUTIC STRATEGIES TO BETTER ADDRESS DEPRESSION ASSOCIATED WITH OUD ARE DESPERATELY NEEDED. 5HT2A AGONISTS (E.G. LYSERGIC ACID DIETHYLAMIDE (LSD) AND PSILOCYBIN) SHOWED THERAPEUTIC PROMISE FOR TREATMENT-RESISTANT DEPRESSION (TRD) IN EARLY STUDIES, BUT RESEARCH INVOLVING THESE PSYCHEDELIC AGENTS FELL PRECIPITOUSLY ONCE THEY WERE CATEGORIZED AS SCHEDULE I BANNED SUBSTANCES IN 1971. ALTHOUGH THE BENEFITS OF 5HT2A AGONISTS ARE BEING RE-DISCOVERED – THE FDA RECENTLY GRANTED “BREAKTHROUGH THERAPY” DESIGNATION TO PSILOCYBIN IN 2018 – PATIENTS MUST REMAIN UNDER OBSERVATION WITH PSYCHOLOGICAL SUPPORT DURING ADMINISTRATION, AND THE THERAPEUTIC IMPACT OF A SINGLE DOSE EVENTUALLY SUBSIDES. AN ALTERNATIVE TREATMENT PARADIGM WITH PROMISE OF RELIEVING MOOD DISORDER AND LESSENING THE LIKELIHOOD OF RELAPSE LONG-TERM IS KNOWN AS MICRODOSING, WHERE SUB-PERCEPTUAL DOSES OF 5HT2A AGONISTS ARE INGESTED EVERY 3-7 DAYS. THOSE WHO MICRODOSE REPORT A RANGE OF BENEFITS INCLUDING IMPROVED MOOD AND DECREASED CRAVING FOR ADDICTIVE SUBSTANCES, AND SCIENTIFICALLY RIGOROUS TRIALS AND PRECLINICAL STUDIES IN ANIMAL MODELS ARE BEGINNING TO CORROBORATE SOME, ALBEIT NOT ALL, OF THE ANECDOTAL CLAIMS. HOWEVER, PRACTICAL BARRIERS SUCH AS LOW COMPLIANCE, ABUSE AND DIVERSION, ACCESS, MEDICAL COST, AND PLACEBO/EXPECTANCY EFFECTS FROM FREQUENT INTERACTIONS WITH THE CLINICAL STAFF STYMIE FURTHER CLINICAL INVESTIGATION INTO THIS PROMISING THERAPEUTIC MODALITY. TO OVERCOME THESE PRACTICAL LIMITATIONS, WE HAVE DEVELOPED BIORESORBABLE MICRODEVICES THAT DELIVER INTERMITTENT SUB-PERCEPTUAL 5HT2A AGONIST MICRODOSES. THE INNOVATION THAT MAKES INTERMITTENT MICRODOSING POSSIBLE IS THE USE OF A MICROFLUIDIC “FUSE" THAT CREATES A PRE-PROGRAMMED DELAY FOR THE DESIRED PULSATILE RELEASE PROFILE. THE FUSES ARE FABRICATED FROM SURFACE- ERODING CELLULOSE ACETATE PHTHALATE (CAP) AND PLURONIC® F-127 (P) POLYMER COMPOSITES PACKED INTO MICROCHANNELS WITHIN A POLY--CAPROLACTONE (PCL) DEVICE BODY. A SERIES OF MICROFABRICATED DRUG RESERVOIRS BENEATH THE CAPP FUSE RELEASE THEIR CONTENTS AS THE FUSE DISSOLVES. THE CURRENT STTR PROPOSAL WILL MOVE THESE DEVICES CLOSER TO CLINICAL RELEVANCE BY PRODUCING DEVICES WITH HIGHLY TAILORED RELEASE PROFILES (AIM 1) AND DEMONSTRATING ABSORPTION AND BIOACTIVITY OF PSILOCYBIN UPON RELEASE FROM THE IMPLANTS (AIM 2). SUCCESS OF THIS PROPOSAL WILL RESULT IN A DISRUPTIVE NEW TECHNOLOGY TO ENABLE MICRODOSING AS A THERAPEUTIC MODALITY AND OFFER MUCH-NEEDED NEW OPTIONS FOR PATIENTS SUFFERING FROM OUD. AFTER ACCOMPLISHING OUR AIMS IN PHASE I, WE WILL BE WELL-POSITIONED TO PURSUE EFFICACY AND BIOCOMPATIBILITY STUDIES, PERFORM PILOT GMP MANUFACTURING, AND SET A PRE- IND MEETING WITH THE FDA THROUGH THE PHASE II STTR/SBIR PROGRAM.
