Advancing PWS Treatments: Key Insights from the Miller 2025 Review

Understanding the Urgent Need for PWS Treatments

Prader-Willi Syndrome (PWS) is a rare, complex neurodevelopmental disorder that affects appetite regulation and can present severe neurobehavioral challenges. While growth hormone remains the only FDA-approved therapy, it does not address the hallmark symptoms of PWS, leaving a critical unmet need.

A recent review by Miller et al. (2025) explores current and emerging therapies aimed at treating hyperphagia and behavioral challenges in PWS.

Investigational Therapies for PWS

Miller et al. (2025) provides an overview of several promising therapies currently in development for PWS. These treatments target different mechanisms, including:

✅ Neurotransmitter modulation to control hyperphagia and behavior

✅ Hormonal therapies influencing appetite-regulating pathways

✅ Gut-targeted therapies aiming to restore metabolic balance

Below is a summary of key investigational therapies discussed in the review:

Current Investigational Therapies for Prader-Willi Syndrome

Therapy	Mechanism of Action	Current Development Status
CSTI-500	Triple monoamine reuptake inhibitor targeting hyperphagia and neuropsychiatric symptoms	Phase II planned
DCCR (Diazoxide Choline)	KATP channel activator reducing appetite-stimulating neuropeptides	Phase III completed; FDA review pending
Carbetocin	Oxytocin analog targeting hyperphagia and obsessive-compulsive behaviors	Phase III ongoing
Oxytocin	Oxytocin modulator affecting social behaviors and hyperphagia	Completed trials with mixed results
ARD-101	Gut-restricted agent triggering anorexigenic hormone release	Phase II completed; Phase III planned
RGH-706	MCH receptor antagonist regulating appetite and metabolism	Phase II completed; awaiting results
Pitolisant	Histamine H3 receptor inverse agonist addressing excessive daytime sleepiness	Phase III ongoing
NNZ-2591	Cyclic glycine proline analog improving cognitive function and behavior	Phase II withdrawn
Cannabidivarin	Non-intoxicating cannabinoid targeting behavioral issues	Completed early-stage trials

CSTI-500: A Novel Approach to Address Hyperphagia and Neuropsychiatric Symptoms

One of the advancements highlighted in the Miller 2025 review is CSTI-500, an innovative therapy in development by ConSynance Therapeutics.

What makes CSTI-500 unique?

Triple monoamine reuptake inhibitor—targets multiple neurotransmitter systems linked to appetite control and behavior.
Demonstrated CNS target engagement in early clinical trials.
Potential to improve hyperphagia AND neuropsychiatric symptoms such as irritabillity, aggression, anxiety, and compulsivity.

At ConSynance, we are committed to developing transformative therapies that address the high unmet medical need in PWS. By targeting both hyperphagia and behavioral challenges, CSTI-500 has the potential to bring meaningful improvements to patients and their families.

The Future of PWS Treatment: A Promising Path Forward

The path to FDA approval for new PWS treatments has been challenging due to clinical trial complexities and limitations in current outcome measures. However, the growing pipeline of innovative therapies - including CSTI-500 and other investigational drugs - offers hope for a brighter future.

The next few months could be pivotal for the PWS community, with the potential approval of DCCR on the horizon. At ConSynance, we are hopeful that any regulatory success will help pave the way for future therapies, accelerating progress and expanding treatment options for individuals living with PWS.

With continued research, collaboration, and advocacy, we remain dedicated to developing transformative therapies that will improve quality of life for patients and their families.

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🔗 Read the full Miller et al. (2025) review on PubMed here: Pharmacological Aspects in the Management of Children and Adolescents with Prader-Willi Syndrome - PubMed