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. 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 | 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 Appetite – These 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 |
Miscellaneous | |||||
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. |
The Foundation for Prader-Willi Research (federal tax id 31-1763110) is a nonprofit corporation with federal tax exempt status as a public charity under section 501(c)(3).
The mission of FPWR is to eliminate the challenges of Prader-Willi syndrome through the advancement of research and therapeutic development.
Foundation for Prader-Willi Research
Phone: 888-322-5487
Email: info@fpwr.org
FPWR
440 N Barranca Ave #3620
Covina, CA 91723
Copyright © 2020. All Rights Reserved. Terms of Use. Privacy Policy. Copyright Infringement Policy. Disclosure Statement.