GlcNAc for NGLY1 Deficiency

Recruiting at 2 trial locations

Overseen By Mary Freeman, MS, CGC

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Eva Morava-Kozicz

Disqualifiers: Shellfish allergy, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

18 Participants Needed

Trial Summary

What is the purpose of this trial?

In patients with NGLY1-CDDG, the disorder can lead to eye damage due to not being able to produce enough tears. This study is being done to see if the dietary supplement, GlcNAc, improves tear production in patients with NGLY1-CDDG.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot have taken GlcNAc within 28 days before starting the trial.

How is the drug GlcNAc-GlcN unique for treating NGLY1 deficiency?

GlcNAc-GlcN is unique because it targets the specific biomarker GlcNAc-Asn, which is associated with NGLY1 deficiency, potentially offering a direct way to monitor and treat this ultra-rare condition, for which there are no standard treatments. ^{1 2 3 4 5}

Research Team

Eva Morava-Kozicz, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for individuals with NGLY1-CDDG, a condition that impairs tear production and can damage the eyes. Participants must have a confirmed diagnosis, be willing to consent (or have a guardian who can consent), and not be planning eye surgery soon or participating in other drug trials.

Inclusion Criteria

My condition is confirmed to be NGLY1-CDDG.

Willingness of subject or legal guardian to provide consent

Parent or legal guardian available to provide consent on behalf of minor subjects or adult subjects who are unable to give informed consent due to developmental disabilities

Exclusion Criteria

You are allergic to any of the ingredients in the placebo.

I am scheduled for eye surgery within the next 3 months.

Participation in another therapeutic trial - the subject will not be permitted to participate in any other drug trial during the blinded phase and during the 28 days prior to Visit 1

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Washout

Participants already on GlcNAc undergo a washout period before consent and randomization

4 weeks

Treatment

Participants receive weight-dependent doses of GlcNAc or placebo for 6 weeks

6 weeks

1 visit (in-person) at 6 weeks

Open-label Treatment

Participants receive open-label weight-dependent doses of GlcNAc for 6 weeks

6 weeks

1 visit (in-person) at 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• GlcNAc-GlcN
• Placebo

Trial Overview The study tests whether GlcNAc, a dietary supplement, increases tear production in those with NGLY1-CDDG. Patients will either receive GlcNAc-GlcN or a placebo without knowing which one they're getting to compare the effects fairly.

Participant Groups

Group I: GlcNAc Experimental Treatment 1 Intervention

GlcNAc powder

Group II: Placebo Placebo Group 1 Intervention

Placebo xylose

Who Is Running the Clinical Trial?

Eva Morava-Kozicz

Lead Sponsor

Trials

4

Recruited

80+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

Findings from Research

N-acetylglucosamine-asparagine (GNA) has been identified as a key biomarker for N-glycanase 1 (NGLY1) deficiency, showing significant differences in levels between affected patients and healthy controls, which can help in identifying patients with this rare disorder.

The study developed a reliable assay to measure GNA levels across various biological samples, demonstrating that elevated GNA levels correlate with the absence of functional NGLY1 and can serve as a potential pharmacodynamic marker and surrogate endpoint in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GlcNAc-Asn is a biomarker for NGLY1 deficiency. Mueller, WF., Zhu, L., Tan, B., et al.[2022]

The first Polish patient diagnosed with NGLY1 deficiency (NGLY1-CDDG) exhibited significant symptoms including global developmental delay, hyperkinetic movement disorder, and hypolacrimia, highlighting the disorder's clinical features.

Whole exome sequencing identified two heterozygous nonsense variants in the NGLY1 gene, reinforcing the importance of genetic testing in diagnosing NGLY1-CDDG, especially in patients with developmental disabilities and movement disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NGLY1 deficiency: Novel patient, review of the literature and diagnostic algorithm. Lipiński, P., Bogdańska, A., Różdżyńska-Świątkowska, A., et al.[2022]

A natural history study involving 29 participants with NGLY1 deficiency revealed severe developmental delays and motor function decline, with most participants scoring below 20 on developmental assessments, indicating significant challenges in growth and development.

The study identified elevated levels of the biomarker GlcNAc-Asn in all participants, which could serve as a potential endpoint for future clinical trials aimed at developing interventions for this rare disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NGLY1 deficiency: a prospective natural history study. Tong, S., Ventola, P., Frater, CH., et al.[2023]

The study identified two novel compound heterozygous mutations in the NGLY1 gene in a 10-month-old infant with NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG), which is linked to developmental delays, epilepsy, and liver dysfunction.

Whole-exome sequencing (WES) and Sanger sequencing were used to confirm these mutations, providing a genetic basis for the disorder in this rare case, which had not been previously documented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two novel compound heterozygous mutations in NGLY1as a cause of congenital disorder of deglycosylation: a case presentation. Ge, H., Wu, Q., Lu, H., et al.[2020]

A patient with NGLY1 deficiency exhibited a milder form of the disorder, lacking many typical symptoms such as severe intellectual disability, which suggests a broader range of possible presentations for this condition.

This case expands the understanding of NGLY1 deficiency, indicating that not all patients will present with the severe symptoms commonly associated with the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the NGLY1 deficiency phenotype: Case report of an atypical patient. Nolan, DK., Pastore, MT., McBride, KL.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

GlcNAc-Asn is a biomarker for NGLY1 deficiency. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

NGLY1 deficiency: Novel patient, review of the literature and diagnostic algorithm. [2022]

3. England pubmed.ncbi.nlm.nih.gov

NGLY1 deficiency: a prospective natural history study. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Two novel compound heterozygous mutations in NGLY1as a cause of congenital disorder of deglycosylation: a case presentation. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Expanding the NGLY1 deficiency phenotype: Case report of an atypical patient. [2022]