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PWS Therapeutics in Development

Many drugs, devices, and other new PWS therapies are currently in development. The development phases range from very early discovery and preclinical studies to active clinical trials (Phase 1, 2, 3) or FDA-approved drugs or devices that are being studied for their safety and efficacy in PWS. The information below provides an overview of the therapeutics in development for PWS. More details of active PWS clinical trials can be found in our clinical trial directory.

Projects denoted with * have been funded through FPWR. We thank our many donors and fundraisers for your contributions to these research programs. You can get involved with FPWR and help fund the development of research tools and therapeutics – click here to learn how!

Approach How It Works Development Phase Investigators / Company
*= FPWR funded
Advantages Potential Limitations
Genetic Therapies – These therapies seek to activate the PWS region genes on the silent maternal chromosome 15 OR provide critical missing genes OR provide a substitute function for PWS genes. These are early stage projects – optimizing approaches and examining feasibility / efficacy in cell and animal models of PWS. Learn more about genetic therapy for PWS >>
Gene activation by small molecules Drugs targeting enzymes that establish / maintain epigenetic marks, activating the PWS genes on the maternal chromosome 15 Discovery / Preclinical * Dr. Jiang Addresses the underlying cause of PWS, so has the potential to profoundly impact symptoms. Would be applicable to all subtypes of PWS (del, UPD, imprinting) Could activate other genes within or outside the PWS region; those consequences are not yet known There may be critical “windows" in which therapy would be effective
CRISPR-based activation Delivery of a specialized gene/protein to specifically target and activate the PWS region on the normally silent maternal chromosome 15 Discovery

* Dr. Nicholls
  * Dr. Lalande

* Dr. Iglesias

Addresses the underlying cause of PWS, so has the potential to profoundly impact symptoms  Applicable to all subtypes. Specificity may be better.
Potential for 1x therapy
Gene delivery likely to be challenging.  Gene therapy is new, so FDA approval path may be difficult. Potential for ‘off target’ effects.
Oligonucleotide therapy Use of small pieces DNA or RNA to modify gene expression Preclinical

* Dr. Chamberlain

Addresses the underlying cause of PWS, so has the potential to profoundly impact symptoms  Dosage may be better titrated than other gene therapy approaches Delivery may be more readily accomplished Need for repeat therapy  Oligonucleotide must be brain penetrant and will probably need to target a large number of cells  – this will be challenging
AAV-Based Gene Activation Delivery of specialized molecules to activate PWS genes Discovery Taysha Gene Therapies Addresses the underlying cause of PWS, so has the potential to profoundly impact symptoms  Applicable to all subtypes. Gene delivery and targeting likely to be challenging.
Epigenome Editing designer epigenome modifiers Discovery * Dr. Mussolino  Addresses the underlying cause of PWS, has the potential to profoundly impact symptoms.  Applicable to all subtypes.  Development and delivery of epigenetic modifiers is at early stage; targeting and delivery will be challenging 
Hyperphagia / Obesity Drugs  These drugs are being evaluated for their ability to curb appetite and/or induce weight loss in people with PWS.
Carbetocin (oxytocin analog) Binds to oxytocin receptors, regulates trust, emotions, appetite Phase 3 completed Levo Therapeutics Potential to address an underlying deficiency in PWS, Oxytocin analog may be more specific to oxytocin receptors, potentially less side effects than oxytocin Not yet FDA approved, may act differently than oxytocin, Long term safety and efficacy in PWS population not yet known
Diazoxide Controlled Release (DCCR) May affect leptin pathways Phase 3 completed * Essentialis, now Soleno Therapeutics New formulation of FDA approved drug   Well defined safety profile – has been used for decades in infants and children with hyperinsulinemia Long term safety and efficacy in PWS population not yet know
Setmelanotide (RM-493) Bypasses proposed POMC neuron defect Phase 2 completed. Trial did not meet standards for efficacy. Rhythm Possibility of targeting underlying defect in hunger circuits Drug may also induce oxytocin release in the brain Efficacy in PWS population not yet clear. Long term safety not yet known
Tesomet A combination of tesofensine and metoprolol to reduce appetite and  induce weight loss Phase 2a completed, Phase 2b underway Saniona Proposed to act by reducing appetite, decreasing food craving and increasing fat utilization Not yet FDA approved  Long term safety not yet known 
Cannabidivarin - CBDV Works through endocannabinoid system Phase 2 enrolling * Dr. Hollander May address both appetite and behavior  Not yet FDA approved  Long term safety not yet known
Aardvark 101 Gut peptide stimulator Phase 2 enrolling * Aardvark Potential to reduce hunger and obesity. Gut restricted. Not yet FDA approved. Long term safety not yet known.
CBD Hyperphagia and behaviors Program halted due to company sale.   Defined formulation of CBD. Potential to address both hyperphagia and anxiety Not yet FDA approved. Long term safety not yet known.
Peripheral Endocannabinoid (CB1R blocker) Decrease activity of endocannabinoid system to decrease appetite Phase 2 pending * Inversago  CB1R induced weight loss in a small PWS study but had side effects; ‘peripheral’ version is expected to have decreased side effects Not yet known if targeting this system peripherally will induce weight loss in PWS
Triple reuptake inhibitor (CSTI500) Hyperphagia Phase 2 pending Consynance Expected to reduce appetite Not yet FDA approved. Long term safety not yet known.
GDD3898 Reduce excess body fat Preclinical Lipidio Topical compound to reduce  excess body fat May not address hunger
GLP Receptor Agonists (exenatide, liraglutide, etc) Suppresses appetite FDA approved, pilot studies in PWS Various FDA approved May improve glucose metabolism, increase satiety May slow gut motility, which can be problematic in PWS, small studies do not show significant weight loss
Behavior and AppetiteThese drugs may cause weight loss and favorably impact behavior / social interaction.
Oxytocin Binds to oxytocin receptors, regulates trust, emotions, appetite Phase 1  ( Miller) AND Phase 2 (Tauber, Einfeld, Hollander, Hokken-Koelega) Dr. Miller       
Dr. Tauber – infant   
* Dr. Tauber – adult    
Dr. Einfeld   
*Dr. Hollander
Potential to address an underlying deficiency in PWS, may address behavior and appetite, FDA approved for other purposes Complex biology, likely to be complex effects There may be specific therapeutic windows depending on age/stage Studies in other disorders (autism) have been mixed thus far
Mental Health
Mindfulness, Cognitive therapies Adaptation of effective behavioral techniques to PWS population Pilot studies Various (see mental health workshop) Safe approach to improve overall well-being Impact may be restricted to a subset of symptoms and/or individuals
Pitolisant Excessive daytime sleepiness Phase 2 complete. Phase 3 opening Q3 2023 Harmony Biosciences Approved for Narcolepsy in the US and the EU. Potential to also impact behavior and cognition. Long-term safety not yet known. 
Oleoyl Serine osteoperosis Preclinical Beryl Addresses an important clinical issue (bone health) that is not fully addressed with current medications Efficacy and long-term safety not yet known
Procedures / Devices   these devices may improve appetite and behavior in PWS 
Transcranial Direct Current Stimulation Treatment used for depression and other neurological disorders that could be applicable for PWS. Pilot * Dr. Butler Used for some disorders (eg, headache).  Noninvasive, generally thought to be safe Does not address underlying cause of disorder so impact may be restricted to subset of symptoms and/or individuals
Vagus Nerve Stimulation Vagus nerve may not communication effectively with brain in PWS Phase 3 opening Q4 2023 FPWR Approved for some mental health problems and epilepsy. New devices are noninvasive Degree of stimulation can be tightly regulated by device Initial studies encouraging, but have been small to date.

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