Natural History Study in Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia

Study Overview
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Brief Summary
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Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare, rapidly progressing, genetic, neurodegenerative disease for which no definitive treatment options and limited information on the natural history of the disease are available. The structural, genetic, and neuropathophysiological abnormalities of ALSP lead to the onset of neurologic symptoms, such as moderate to severe motor and neuropsychiatric impairments. This natural history study will collect data to contribute to the development of future novel therapies that focus on the neuropathophysiological features that underlie ALSP and that are essential to reverse, delay, or stop progression of this debilitating disorder.

Official Title
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A Natural History Study of Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia (ALSP)

Conditions
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ALSP

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria for both Definitive ALSP patients and Prodromal ALSP patients: 1. Subjects who have documentation of a gene mutation in the CSF1R gene Key Inclusion Criteria for Definitive ALSP patients, only: Subjects who fulfill both of the following criteria (a and b): a. More than two findings of clinical signs or symptoms in the following categories: i. Cognitive impairment or psychiatric problem ii. Pyramidal signs on neurological examination iii. Extrapyramidal signs, such as rigidity, tremor, abnormal gait, or bradykinesia iv. Epilepsy b. MRI findings consistent with ALSP: specifically, bilateral cerebral white matter lesions with or without thinning of the corpus callosum NOTE: Subjects with other causes of leukoencephalopathy, including vascular dementia, multiple sclerosis, or leukodystrophy (e.g., adrenoleukodystrophy, Krabbe disease, metachromatic leukodystrophy), will be excluded. Subjects who, in the investigator's opinion, have demonstrated clinical progression of their ALSP within the past year. Subjects who meet the criteria for definitive ALSP must have a designated caregiver who spends at least 4 hours per week with them. The caregiver must be able and willing to assist the subject in complying with the study requirements, be able to provide information during study visits, and be willing to sign a caregiver ICF. Key Inclusion Criteria for Prodromal ALSP patients, only: 1. MRI findings consistent with ALSP: specifically, bilateral cerebral white matter lesions with or without thinning of the corpus callosum. Prodromal subjects may have none or up to and including 2 ALSP-related clinical signs or symptoms (i.e., they do not meet the clinical criteria outlined in the Definitive ALSP as more than two). Key Exclusion Criteria (for all study participants): Subjects with any neurological or psychiatric diseases that can produce cognitive, motor, or behavioral impairment similar to ALSP, including, but not limited to, Alzheimer's disease, frontotemporal dementia, ALS, stroke, Huntington disease, multiple sclerosis, Parkinson's disease, and Down syndrome, or with active alcohol/drug abuse Subjects who are unable to undergo MRI Subjects with any condition or situation that, in the opinion of the investigator or sponsor medical personnel, may place the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study. Subjects who have previously undergone HSCT or plan to undergo HSCT within 12 months of the Screening/Baseline visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with ALSP<br> | Other: No intervention<br>* Not applicable for a Natural History Study<br>|
| Patients with Prodromal ALSP<br> | Other: No intervention<br>* Not applicable for a Natural History Study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnetic Resonance Imaging (MRI) | Change from Baseline in structural and volumetric MRI | Months 6, 12, 18, 24, 30, and 36 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hereditary Diffuse Leukoencephalopathy with Spheroids, HDLS, CSF1R-related Leukoencephalopathy, Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia, CSF1R gene mutation, POLD, Pigmentary Orthochromatic Leukodystrophy, ALSP, CSF1R, leukoencephalopathy