Amino AcidsGlycine

NNZ-2591 improves sleep in children and adolescents with Phelan-McDermid syndrome

In an open-label phase 2 trial, NNZ-2591 was associated with significant improvements in sleep assessments among 18 children and adolescents with Phelan-McDermid syndrome after 13 weeks of treatment. Sleep was one of 14 secondary efficacy endpoints, with significant improvement from baseline observed at week 13.

Last updated: Aug 26, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score38/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. NNZ-2591 in Children and Adolescents With Phelan-McDermid Syndrome: Single-Group, Open-Label, Phase 2 Trial Results.

observational

Neumeyer AM, Srivastava S, Holder JL, Milad MA, Squires L, Jones NE, Glass L, Berry-Kravis E · Neurology. Genetics (2025)

Participants: N/A
Duration: 13 weeks
Intervention: NNZ-2591 (synthetic analog of cyclic glycine-proline) administered orally twice daily, uptitrated from 4 mg/kg to 12 mg/kg over 6 weeks, then maintained for 13 weeks total
Outcome: Sleep assessments (part of secondary efficacy endpoints)
Effect Size: N/A (specific effect size for sleep not reported; p < 0.05 for sleep assessment improvement)
Population: Children and adolescents aged 3-12 years with Phelan-McDermid syndrome (mean age 8.6 years, mean weight 30.4 kg)

Result:

PubMed: 41450730DOI: 10.1212/NXG.0000000000200338

Mechanism Graph

NNZ-2591 is a synthetic analog of cyclic glycine-proline, a metabolite of insulin-like growth factor 1
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It modulates neurotrophic signaling pathways relevant to neurodevelopment
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Improves synaptic function and neural connectivity in PMS
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Result: Clinically meaningful improvements in sleep and other PMS symptoms

Limitations

  • ⚠Open-label design with no placebo control, limiting causal inference
  • ⚠Small sample size (n=18) reduces generalizability and statistical power
  • ⚠Sleep was a secondary endpoint and not assessed with validated sleep-specific instruments

Frequently Asked Questions

What is NNZ-2591?▼

NNZ-2591 is a synthetic analog of cyclic glycine-proline, a metabolite of insulin-like growth factor 1, being tested for Phelan-McDermid syndrome.

Did NNZ-2591 improve sleep in this study?▼

Yes, sleep assessments showed significant improvement from baseline at week 13 in children and adolescents with PMS.

What were the main side effects of NNZ-2591?▼

NNZ-2591 was well tolerated; most treatment-emergent adverse events were mild to moderate.

Is NNZ-2591 approved for PMS?▼

No, this is a phase 2 trial; the drug is not yet approved. Further evaluation is ongoing.

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References

  1. 1.Neumeyer AM, Srivastava S, Holder JL, Milad MA, Squires L, Jones NE, Glass L, Berry-Kravis E. "NNZ-2591 in Children and Adolescents With Phelan-McDermid Syndrome: Single-Group, Open-Label, Phase 2 Trial Results.." Neurology. Genetics, 2025. PMID: 41450730 DOI: 10.1212/NXG.0000000000200338
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.