Related Experiment Video
Updated: Jul 23, 2025
Eye-Tracking Control to Assess Cognitive Functions in Patients with Amyotrophic Lateral Sclerosis
Published on: October 13, 2016
Evaluating meaningful changes in physical functioning and cognitive declines in metachromatic leukodystrophy: a
Susan Martin1, Nimanee Harris2, Dorothy Romanus3
1RTI Health Solutions, Ann Arbor, MI, USA. smartin@rti.org.
Background:
Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disease caused by deficient activity of arylsulfatase A (ASA). Treatment options for patients are limited; gene therapy based on haematopoietic stem cell transplantation is the only approved treatment for some subtypes of MLD. Any therapeutic benefit of treatments must be meaningful for patients and their families. We evaluated the clinical meaningfulness of slowing the decline in gross motor function as measured by the Gross Motor Function Classification in MLD (GMFC-MLD) from the caregiver perspective via semi-structured telephone interviews with caregivers of children with late-infantile MLD. We also evaluated the perceived significance of declines in communication abilities measured by the Expressive Language Function Classification in MLD (ELFC-MLD). This work could help to inform the endpoints of a phase 2 clinical trial (NCT03771898) assessing the efficacy of intrathecal recombinant human ASA in MLD.
Results:
Twelve caregivers were recruited, reporting on 12 children with MLD. Children had a mean age of 6.1 years; mean age at symptom onset was 17.6 months. Most children (10/12) progressed from walking without support (categories 0-1) to a loss of locomotion (categories 5-6) in ≤ 2 years. Caregivers felt that GMFC-MLD and ELFC-MLD accurately described motor and language declines in their children, respectively. Most caregivers (10/12) reported that the idea of delaying disease progression would be meaningful. Further, a slowing of motor function decline in GMFC-MLD, from category 1 to category 3 or from category 2 to category 4 over 2 years, was seen as meaningful by all caregivers asked; however, only 3/12 caregivers reported that delayed decline would be meaningful if baseline category was ≥ 3. Caregivers also reported that delaying expressive language decline at any level that did not indicate a complete loss of expressive language (indicated by categories 1-3) would be meaningful.
Conclusions:
Caregivers of children with MLD felt that a delayed decline in gross motor function, as assessed by the GMFC-MLD, would be meaningful, supporting the selection of primary and secondary endpoints for the phase 2 clinical trial. Communication abilities were another area of significance for consideration in future clinical trial design.
Insights
Caregivers find delaying motor and language decline meaningful for children with Metachromatic Leukodystrophy (MLD). This supports using Gross Motor Function Classification in MLD (GMFC-MLD) and Expressive Language Function Classification in MLD (ELFC-MLD) as trial endpoints.
Area of Science:
- Neurology
- Genetics
- Lysosomal Storage Diseases
Background:
- Metachromatic leukodystrophy (MLD) is a rare genetic disorder affecting the nervous system due to arylsulfatase A (ASA) deficiency.
- Current MLD treatments are limited, with gene therapy via hematopoietic stem cell transplantation being the only approved option for specific subtypes.
- Assessing the clinical meaningfulness of therapeutic benefits from the patient and caregiver perspective is crucial for treatment evaluation.
Purpose of the Study:
- To evaluate the clinical meaningfulness of slowing gross motor function decline, measured by the Gross Motor Function Classification in MLD (GMFC-MLD), from the caregiver perspective.
- To assess the perceived significance of declines in communication abilities, measured by the Expressive Language Function Classification in MLD (ELFC-MLD).
- To inform the selection of endpoints for a Phase 2 clinical trial investigating intrathecal recombinant human ASA in MLD.
Main Methods:
- Semi-structured telephone interviews were conducted with caregivers of children diagnosed with late-infantile MLD.
- Caregivers reported on the motor and language progression of their children using the GMFC-MLD and ELFC-MLD scales.
- The study focused on understanding caregiver perceptions of meaningful delays in disease progression.
Main Results:
- Most caregivers (10/12) perceived delaying MLD progression as meaningful.
- A slowing of motor function decline (e.g., GMFC-MLD category 1 to 3 over 2 years) was considered meaningful by all caregivers asked.
- Caregivers found delaying expressive language decline meaningful, particularly when it did not indicate a complete loss of communication (ELFC-MLD categories 1-3).
Conclusions:
- Caregiver perspectives strongly support the meaningfulness of delaying gross motor function decline in MLD, validating GMFC-MLD as a key clinical trial endpoint.
- Communication abilities, assessed via ELFC-MLD, are also significant and should be considered in future clinical trial designs.
- These findings will help refine the endpoints for ongoing and future MLD clinical trials, ensuring therapeutic benefits align with patient and family priorities.
Related Concept Videos
01:30Cognitive Development During Adulthood
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
01:30Dementia
The progression of dementia is generally gradual....