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Principal Investigator: Mohammed Adnan Mohammed Hanif Qureshi
Organization: NEMALIFE INC.
Fiscal Year: 2024
Award: $322,070
Funding agency: National Institute on Alcohol Abuse and Alcoholism
Project Abstract
Alcohol use disorders (AUDs) are globally prevalent neurobehavioral disorders where individuals consume
excessive alcohol despite its adverse effects on their lives. The global incidence of deaths related to AUDs was
estimated at 3 million in 2016, while in the US, 140,000 deaths annually are alcohol-related. While there are
FDA-approved treatments for AUDs, they require chronic treatment to remain effective. In contrast, psychedelics
offer a potential paradigm shift in addiction treatment because a single dose can cause long-lasting abstinence
from alcohol. However, natural psychedelics, such as ibogaine, have serious side effects that make them
unsuitable neurotherapeutics. Pyschoplastogens are non-hallucinogenic derivatives of psychedelics with
improved safety profiles that make them good candidates for new neurotherapeutics for AUDs. NemaLife, Inc.’s
Infinity Screening System 2.0 (ISS 2.0) is a high-throughput in vivo screening platform that uses the nematode
Caenorhabditis elegans for drug discovery. ISS 2.0 records video data that is automatically processed by our AI
pipeline for metrics such as live/dead and animal activity. This Phase 1 project will combine the novelty of a
targeted psychoplastogen library and new machine learning-based behavioral screening. This foundational
capability will allow us to perform AI-assisted behavioral profiling of worm models of AUDs to screen for new
neurotherapeutics for alcohol addiction.
AIM 1: Develop high-throughput AI-assisted behavioral profiling assays for alcohol use disorders
The ISS 2.0 platform offers the ability to conduct high-throughput drug screens using the nematode C. elegans.
In Aim 1, we will optimize assays for alcohol use disorder and test a series of well-established psychedelic
compounds to identify positive controls. We will examine two AUD paradigms and develop behavioral metrics.
Finally, we will correlate these metrics to create phenotypic profiles of animals exhibiting AUD behavior, which
will be used to train and implement additional machine learning algorithms into ISS 2.0 to allow it to distinguish
between addictive and non-addictive behavior in real-time.
AIM 2. Identify potential AUD therapeutics from a targeted library of psychoplastogens
Psychoplastogens have better safety profiles than psychedelics and might make effective treatments for AUDs.
We can leverage our AI-enabled platform for screening psychoplastogens and establishing their therapeutic
value. Therefore, we propose to use the ISS 2.0 behavioral profiling capabilities developed in Aim 1 to screen
about 200 compounds for their potential as therapeutics for AUD. We will then characterize the potential
mechanisms of action of the hits through transcriptomic profiling, laying the groundwork for future studies using
rodent models of AUD in a Phase 2 application. Combining rapid identification of anti-addictive compounds with
high-throughput worm screens and validation in rodent models will significantly de-risk clinical trials of lead
candidates and accelerate the development of next-generation AUD treatments.
Terms: <12-Methoxyibogamine><12-methoxy-ibogamine><Abstinence><Acceleration><Address><Adverse effects><Agar><Age><Alcohol Chemical Class><Alcohol dependence><Alcohols><Animal Behavior><Animal Model><Animal Models and Related Studies><Animals><Antabuse><Assay><Behavior><Behavior Disorders><Behavioral><Bioassay><Biologic Sciences><Biological Assay><Biological Sciences><Bioscience><Brain><Brain Nervous System><C elegans><C. elegans><C.elegans><Caenorhabditis elegans><Cessation of life><Chronic><Clinical Trials><Custom><Data><Death><Development><Disulfiram><Dose><Drugs><Elements><Encephalon><Exhibits><FDA approved><Future><Hallucinogenic Agents><Hallucinogenic Drugs><Hallucinogenic Substances><Hallucinogens><Heavy Drinking><High Throughput Assay><Humidity><Ibogaine><Illumination><Image><Incidence><Individual><Invertebrata><Invertebrates><Knowledge><Laboratories><Libraries><Life Sciences><Lighting><Machine Learning><Mammalia><Mammals><Marketing><Medication><Microfluidic Device><Microfluidic Lab-On-A-Chip><Microfluidic Microchips><Microfluidics><Modeling><N-acetylhomotaurine><Nalorex><Naltrexone><Nematoda><Nematodes><Nemexin><Pharmaceutical Preparations><Phase><Phenotype><Population><Process><Property><Protocol><Protocols documentation><Psychedelic Agents><Psychedelics><Psychotomimetic Agents><Publishing><Pump><ReVia><Risk><Rodent Model><Safety><Self Administered><Self Administration><Series><Source><Substance Use Disorder><System><Temperature><Testing><Tetraethylthiuram Disulfide><Therapeutic><Time><Training><United States><Validation><Video Recording><Videorecording><Visual><Vivitrol><Work><abstaining from alcohol><abstaining from ethanol><abstinence from alcohol><abstinence from ethanol><acamprosate><acamprostate><addiction><addictive disorder><ages><alcohol abstinence><alcohol abuse therapy><alcohol abuse treatment><alcohol addiction><alcohol dependency><alcohol dependent><alcohol treatment><alcohol use disorder><alcohol-related death><analog><behavioral disorder><chemical synthesis><clinical risk><compulsion><customs><developmental><drink heavily><drug discovery><drug use screening><drug/agent><economic cost><effective therapy><effective treatment><ethanol abstinence><ethanol use disorder><excessive alcohol consumption><excessive alcohol ingestion><excessive alcohol intake><excessive drinking><excessive ethanol ingestion><extreme drinking><feeding><heavy alcohol use><high dimensionality><high throughput screening><high-throughput drug screening><imaging><improved><in vivo><innovate><innovation><innovative><lead candidate><machine based learning><machine learned algorithm><machine learning algorithm><machine learning based algorithm><microfluidic chip><model of animal><neurobehavioral disorder><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><programs><psychedelic drug><psychotomimetic drug><roundworm><screening><screenings><sensor><side effect><societal costs><substance use and disorder><transcriptome profiling><transcriptomic profiling><transcriptomics><validation studies><validations><video recording system><µfluidic>