A Natural History Study of Aspartylglucosaminuria (AGU)

Aspartylglucosaminuria (AGU) is a rare neurodegenerative lysosomal storage disease (LSD) characterized by developmental delay, psychomotor regression, worsening intellectual disability, gait disturbance and, ultimately, premature death, and has no available treatments.

The purpose of this study is to investigate the clinical characteristics and natural clinical progression of symptoms in individuals with AGU. This natural history study is important to better understand disease course to be able to determine clinically meaningful outcome measures for use in future clinical trials.

Study Overview

• Status: Terminated
• Conditions: Lysosomal Storage Diseases; Aspartylglucosaminuria; Aspartylglucosamidase (AGA) Deficiency

Detailed Description

Lysosomal storage disorders (LSDs) are a group of inherited metabolic diseases caused by a genetic mutation resulting in deficiency or absence of a critical enzyme, leading to the accumulation of toxic deposits in cells across multiple organ systems.

Aspartylglucosaminuria (AGU) is a rare, neurodegenerative, LSD, caused by a deficiency of the aspartylglucosaminidase (AGA) enzyme, which leads to toxic accumulation of aspartylglucosamine and subsequent cellular dysfunction. AGU has been most commonly reported in people of Finnish and Nordic descent, but is present across ethnicities and is typically misdiagnosed or undiagnosed.

Aspartylglucosaminuria (AGU) is characterized by developmental delay and intellectual disability that worsens with age. Early disease is characterized by increased frequency of bacterial ear infections, recurrent ear tube placement, intestinal dysfunction, disruptive sleep patterns, skeletal abnormalities, and gait disturbances, among others. Individuals progressively lose motor and cognitive skills, develop behavioral/emotional lability and their risk of seizures increases with age. People with AGU have a shortened life span.

No prospective natural history study for AGU has been reported. This study aims to prospectively investigate the natural history of AGU, and concurrently to identify potential outcome measures that could be used in future clinical trials. No investigational product will be provided in the study.

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with a confirmed genetic diagnosis of aspartylglucosaminuria.

Description

Inclusion Criteria:

• Participants must have a diagnosis of AGU based on clinical presentation and genetic testing (known or suspected pathogenic mutation in AGA gene).

Exclusion Criteria:

• Patients unable to travel to UT Southwestern Medical Center and Children's Health Dallas will not be enrolled in the prospective natural history study collecting standardized clinical data; however, with participant consent, medical records will be obtained, reviewed, and recorded in the natural history database over time.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological Testing	Participants will undergo a standardized neuropsychological evaluation every 6-12 months, depending upon the assessments as follows: Global Cognitive: Leiter International Performance Scale, 3rd Ed, Reynolds Intellectual Assessment Scales, 2nd Ed, Mullen Scales of Early Learning Emotional: Aberrant Behavior Checklist, 2nd Ed, Behavior Assessment System for Children, 3rd Ed Behavioral functioning: Aberrant Behavior Checklist, 2nd Ed, Behavior Assessment System for Children, 3rd Ed	5 years
Ophthalmological Evaluation	Participants will undergo an ophthalmological assessment every 6 months to better characterize the involvement of the eye in AGU.	5 years
Visual Evoked Potential (VEP)	Participants will undergo a VEP test every 6 months to evaluate electrical signal transmission through the visual pathway from the retina to the visual cortex.	5 years
Brainstem Auditory Evoked Response (BAER)	Participants will undergo a BAER test every 6 months to evaluate electrical signal transmission from the 8th cranial nerve to the brainstem and the cortex in response to certain tones.	5 years
Magnetic Resonance Imaging (MRI)/Magnetic Resonance Spectroscopy (MRS)	An MRI scan of the brain will be performed annually to characterize the structural abnormalities associated with AGU. MRS will be performed on regions of interest in the brain.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adaptive functioning: Vineland Adaptive Behavior Scales, 3rd Ed	Participants will undergo a standardized neuropsychological evaluation every 6-12 months	5 years
Language: Expressive One-Word Picture Vocabulary Test, 4th Ed, Receptive One-Word Picture Vocabulary Test, 4th Ed, NEPSY, 2nd Ed	Participants will undergo a standardized neuropsychological evaluation every 6-12 months	5 years
Motor: NIH Toolbox Early Childhood Motor Battery or NIH Toolbox Motor Battery, 6 Minute Walk Test, Beery-Buktenica Development	Participants will undergo a standardized neuropsychological evaluation every 6-12 months	5 years

Collaborators and Investigators

• Sponsor: Neurogene Inc.
• Investigators: Study Director: Elise Beausoleil, Neurogene Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2019
• Primary Completion (Actual): October 15, 2020
• Study Completion (Actual): March 17, 2022

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: February 21, 2019
• First Posted (Actual): February 26, 2019

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Aspartylglucosaminuria
• Other Study ID Numbers: AGU-100

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No