A Prospective Natural History Study of Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) (S49.008)
2023-04-25

<h3>Objective:</h3> Characterize the natural history of ALSP by imaging, biomarkers, and standardized clinical measurements to inform the design of future clinical trials testing novel therapeutics for ALSP. <h3>Background:</h3> ALSP is a rare, rapidly progressing fatal neurologic disorder commonly caused by dominant variants in the <i>CSF1R</i> gene. The pathological hallmarks include demyelination of brain white matter, swollen axons, and pigmented glial cells. Clinically, ALSP is characterized by a constellation of symptoms including personality changes, cognitive dysfunction and motor impairments. There are no FDA approved treatments for ALSP. Limited natural history data is available to inform development of therapeutics for ALSP. <h3>Design/Methods:</h3> This is a prospective, multicenter, natural history study of patients with ALSP and asymptomatic carriers of <i>CSF1R</i> gene mutations. Up to 36 participants will be enrolled and followed for 24 months. Clinical assessments (cognitive, motor, functional, psychiatric, severity of illness, and caregiver burden) and MRI will be collected at Screening and at months 6, 12, 18, and 24. MRI severity score (Sundal et al 2012), white matter lesion and regional brain volumes will be derived. Blood and CSF (in a subset of participants) biomarkers of disease will be measured at specific visits. <h3>Results:</h3> 28 participants with confirmed <i>CSF1R</i> gene mutation meeting study eligibility criteria have been enrolled as of 9/2/2022. Among these, 17 were symptomatic and 11 were asymptomatic carriers, 13 were women and mean age at Screening visit was 46±13 years. Study enrollment is ongoing. Detailed study design and baseline characteristics of enrolled participants will be presented. <h3>Conclusions:</h3> This is the first systematic prospective study characterizing the natural history of ALSP due to <i>CSF1R</i> gene mutations leveraging standardized clinical, imaging and biomarker measurements. The outcome of this study is expected to inform on optimal biomarker and clinical endpoints and design of therapeutic intervention studies in ALSP. <b>Disclosure:</b> Dr. Rajagovindan has received personal compensation for serving as an employee of Biogen. Dr. Rajagovindan has received personal compensation for serving as an employee of Vigil. Dr. Rajagovindan has stock in Biogen. Dr. Rajagovindan has stock in Vigil . Mr. Matys has received personal compensation for serving as an employee of Vigil Neuroscience. Dr. Finger has received personal compensation in the range of 4,999 for serving as a Consultant for Vigil Neuro. Dr. Finger has received personal compensation in the range of 4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Denali Therapeutics. The institution of Dr. Finger has received research support from CIHR. The institution of Dr. Finger has received research support from Physician Servcices Incorporated. The institution of Dr. Finger has received research support from Weston Foundation. Dr. Finger has received personal compensation in the range of 4,999 for serving as a Annual Meeting Course Director with American Academy of Neurology. An immediate family member of Dr. Gelfand has received personal compensation in the range of 99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Headache: The Journal of Head and Face Pain. The institution of Dr. Gelfand has received research support from Genentech/Roche. The institution of Dr. Gelfand has received research support from Vigil Neurosciences. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received personal compensation in the range of 49,999 for serving as a Consultant and Expert, Vaccine Injury Compensation Program with United States Health and Human Services and Department of Justice. Dr. Gelfand has a non-compensated relationship as a Trial Steering Committee Chairperson and member with Roche / Genentech that is relevant to AAN interests or activities. Wolfgang Koehler has received personal compensation in the range of 49,999 for serving as a Consultant for Minoryx. Wolfgang Koehler has received personal compensation in the range of 4,999 for serving as a Consultant for Vigil. Wolfgang Koehler has received personal compensation in the range of 4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for United Leukodystrophy Foundation. Wolfgang Koehler has received personal compensation in the range of 499 for serving on a Scientific Advisory or Data Safety Monitoring board for European Leukodystrophy Association. The institution of Wolfgang Koehler has received research support from Minoryx. The institution of Wolfgang Koehler has received research support from Vigil. The institution of Wolfgang Koehler has received research support from SwanBio. The institution of Wolfgang Koehler has received research support from Alexion. The institution of Dr. Kumar has received personal compensation in the range of 99,999 for serving as a Consultant for Supernus. The institution of Dr. Kumar has received personal compensation in the range of 49,999 for serving as a Consultant for Abbvie. The institution of Dr. Kumar has received personal compensation in the range of 499,999 for serving as a Consultant for Teva Pharmaceuticals. The institution of Dr. Kumar has received personal compensation in the range of 49,999 for serving as a Consultant for Annexon. The institution of Dr. Kumar has received personal compensation in the range of 9,999 for serving as a Consultant for Roche. The institution of Dr. Kumar has received personal compensation in the range of 49,999 for serving as a Consultant for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of 9,999 for serving as a Consultant for Cerevel Therapeutics. Dr. Kumar has received personal compensation in the range of 9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel Pharma. Dr. Kumar has received personal compensation in the range of 99,999 for serving on a Speakers Bureau for Supernus. The institution of Dr. Kumar has received personal compensation in the range of 499,999 for serving on a Speakers Bureau for Teva. The institution of Dr. Kumar has received personal compensation in the range of 49,999 for serving on a Speakers Bureau for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of 49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Kumar has received personal compensation in the range of 100,000- 1,000,000+ for serving as a Managing Member with Research Catalyst, LLC. Dr. Lynch has received personal compensation in the range of 9,999 for serving as a Consultant for Vigil Neuroscience. Dr. Orthmann Murphy has received research support from Conrad N. Hilton Foundation. Dr. Orthmann Murphy has received research support from Institute for Translational Medicine and Therapeutics' (ITMAT) Transdisciplinary Program in Translational Medicine and Therapeutics, University of Pennsylvania. The institution of Dr. Orthmann Murphy has received research support from Vigil Neurosciences. The institution of Dr. Orthmann Murphy has received research support from National MS Society. Dr. Orthmann Murphy has received personal compensation in the range of 4,999 for serving as a Invited Speaker with Temple University . Dr. Orthmann Murphy has received personal compensation in the range of 499 for serving as a Consultant with American Neurological Association. Dr. Schols has received personal compensation in the range of 4,999 for serving as a Consultant for VICO Therapeutics. Dr. Schols has received personal compensation in the range of 4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Schols has received research support from Vigil. The institution of Nicole Wolf has received research support from ZonMW. Andreas Meier has received personal compensation for serving as an employee of Voyager Therapeutics. Andreas Meier has received personal compensation for serving as an employee of Biogen. Dr. Papapetropoulos has received personal compensation for serving as an employee of Vigil Neuroscience . Dr. Papapetropoulos has received personal compensation in the range of 499,999 for serving as a Consultant for Acadia. Dr. Papapetropoulos has received personal compensation in the range of 49,999 for serving as a Consultant for Ventus Therapeutics Inc. Dr. Papapetropoulos has received personal compensation in the range of 49,999 for serving as an officer or member of the Board of Directors for Adamas Pharmaceuticals. Dr. Papapetropoulos has received personal compensation in the range of 49,999 for serving as an officer or member of the Board of Directors for Lipocine Inc. Dr. Papapetropoulos has stock in Vigil Neuroscience. Dr. Papapetropoulos has stock in Adamas. Dr. Papapetropoulos has stock in Lipocine. Dr. Wszolek has received personal compensation in the range of 9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Polish Neurological Society/Via Medica.