Many drugs, devices and other therapeutics are currently in development for the treatment of PWS. The development phases range from very early (discovery/preclinical) to active clinical trials (Phase 1, 2, 3) or FDA approved drugs that are being studied for their safety/efficacy in 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 1 completed * Essentialis 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 ongoing 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
AZP-531 Unacylated ghrelin to decrease the hunger-inducing effects of acylated ghrelin Phase 2 completed Alize 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 2 planned 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
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 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
Oxytocin Analog, FE992097 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
antibiotic May improve hypotonia by facilitating nerve/muscle interaction Pilot studies Dr. Creemers Drug approved for other uses Underlying cause of hypotonia in PWS not yet well defined
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. Phase 1 * 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 1 * 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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