Many drugs, devices and other new PWS therapies are currently in development. The development phases range from very early (discovery/preclinical) to active clinical trials (Phase 1, 2, 3) or FDA approved drugs/devices that are being studied for their safety/efficacy in PWS. More details of active PWS clinical trials can be found on this page; the information below provides an overview of the therapeutics in development for PWS.
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. | |||||
| 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 |
| TALE – based activation | Delivery of a gene or protein to specifically target and activate the PWS region on the normally silent maternal chromosome 15 | Discovery | * Dr. Segal | 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 |
| 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 | 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 | Replacement of function of PWS region genes using small pieces DNA or RNA | Preclinical | *Dr. Stamm | 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 |
| Hyperphagia / Obesity Drugs – these drugs are being evaluated for their ability to curb appetite and/or induce weight loss in people with PWS | |||||
| PeripheralEndocannabinoid (CB1R blocker) | Decrease activity of endocannabinoid system to decrease appetite | Preclinical | * Dr. Tam | CB1R induced weight loss in a small PWS study but had side effects; ‘peripheral’ version is expected to have decreased side effects | Early in development Not yet clear if targeting this system peripherally will induce weight loss in PWS |
| Diazoxide Controlled Release (DCCR) | May affect leptin pathways | Phase 3 planning | * Essentialis , now Soleno | New formulation of FDA approved drug Well defined safety profile – has been used for decades in infants and children with hyperinsulinemia | Long term safety in PWS population not yet know |
| Setmelanotide (RM-493) | Bypasses proposed POMC neuron defect | Phase 2 completed | Rhythm | Possibility of targeting underlying defect in hunger circuits Drug may also induce oxytocin release in the brain | Not yet FDA approved Long term safety not yet known |
| Livoletide (AZP-531) | Unacylated ghrelin to decrease the hunger-inducing effects of acylated ghrelin | Phase 2 completed, Phase 3 planning | Millendo | Has the potential to address PWS-specific increase in ghrelin | Not yet FDA approved, Long term safety not yet known |
| Tesomet | A combination of tesofensine and metoprolol to induce weight loss | Phase 2a completed | Saniona | Proposed to act by reducing appetite, decreasing food craving and increasing fat utilization | Not yet FDA approved Long term safety not yet known |
| Cannabidoil (CBD) oral solution | Suppresses appetite, reduce anxiety | Phase 2 planned | Insys | May address both appetite and behavior | Not yet FDA approved Long term safety not yet known |
| GLWL-01 | Reduces active ghrelin | Phase 2 | GLWL | ||
| GLP Receptor Agonists (exenatide, liraglutide, etc) | Supresses 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 |
| Carbetocin (oxytocin analog) | Binds to oxytocin receptors, regulates trust, emotions, appetite | Phase 2 (completed), Phase 3 pending | 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 |
| Mental Health | |||||
| Mindfulness, Cognitive therapies | Adaptation of effective behavioral techniques to PWS population | Pilot studies | Various (see MH workshop) | Safe approach to improve overall well-being | Impact may be restricted to a subset of symptoms and/or individuals |
| Miscellaneous | |||||
| Myostatin inhibitor / activin receptor | Builds muscle mass | Preclinical | various companies | Increased muscle mass might improve metabolism, endurance and quality of life in PWS | Early clinical studies in other disorders (e.g., muscular dystrophy) did not shown positive effects |
| 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 | Pilot | * Dr. Holland | Approved for obesity disorders New devices are noninvasive Degree of stimulation can be tightly regulated by device | Effects variable in small pilot study Potential side effects on speech |
| Deep Brain Stimulation | Stimulation of specific areas of the brain to control eating | Proposed, not yet in progress | Dr. Halpern | Appears to have positive effects in some other disorders (depression, Parkinson disease) | Rare but serious surgical complications possible |
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