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

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

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.

Key Inclusion Criteria for Definitive ALSP patients:

1. Subjects who have documentation of a gene mutation in the CSF1R gene (prior to enrollment)

2. 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.

3. Subjects who, in the investigator's opinion, have demonstrated clinical progression of their ALSP within the past year.

4. Subjects who meet the criteria for definitive ALSP must have a designated study partner (i.e caregiver) who spends at least 4 hours per week with them. The study partner 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 study partner ICF. Subjects who do not have a study partner may be enrolled at the investigator's discretion if they are able to comply with protocol requirements.

Key Exclusion Criteria for Definitive ALSP patients:

1. 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
2. Subjects who are unable to undergo MRI
3. 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.
4. Subjects who have previously undergone HSCT or plan to undergo HSCT within 12 months of the Screening/Baseline visit.