Abstract Details

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

Topic General Neurology

Presentation(s) S49 - General Neurology (4:54 PM-5:06 PM)

Poster/Presentation
Number 008

Background

ALSP is a rare, rapidly progressing fatal neurologic disorder commonly caused by dominant variants in the CSF1R 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.

Objective

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.

Design/Methods This is a prospective, multicenter, natural history study of patients with ALSP and asymptomatic carriers of CSF1R 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.

Results

28 participants with confirmed CSF1R 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.

Conclusions

This is the first systematic prospective study characterizing the natural history of ALSP due to CSF1R 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.

Authors/Disclosures
Rajasimhan Rajagovindan, PhD (Vigil) PRESENTER	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 .
Benjamin Matys (Vigil Neuroscience)	No disclosure on file
Elizabeth Finger, MD, FAAN	Dr. Finger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vigil Neuro. Dr. Finger has received personal compensation in the range of $500-$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 $500-$4,999 for serving as a Annual Meeting Course Director with American Academy of Neurology.
Jeffrey M. Gelfand, MD, MAS, FAAN (University of California, San Francisco)	Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ventyx Bio. An immediate family member of Dr. Gelfand has received personal compensation in the range of $50,000-$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 $10,000-$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.
	No disclosure on file
Wolfgang Koehler (University of Leipzig Medical Center)	Wolfgang Koehler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Minoryx. Wolfgang Koehler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vigil. Wolfgang Koehler has received personal compensation in the range of $500-$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 $0-$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.
Rajeev Kumar, MD, FRCPC (Rocky Mountain Movement Disorders Center)	The institution of Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Teva Pharmaceuticals. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Annexon. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cerevel Therapeutics. Dr. Kumar has received personal compensation in the range of $5,000-$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 $50,000-$99,999 for serving on a Speakers Bureau for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Teva. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Research Catalyst, LLC. Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for CenExel RMCR. Dr. Kumar has stock in Research Catalyst, LLC. Dr. Kumar has stock in CenExel. The institution of Dr. Kumar has received research support from Supernus. The institution of Dr. Kumar has received research support from Sage Therapeutics. The institution of Dr. Kumar has received research support from Prilenia Therapeutics. The institution of Dr. Kumar has received research support from Roche. The institution of Dr. Kumar has received research support from Triplet Therapeutics. The institution of Dr. Kumar has received research support from CHDI Foundation. The institution of Dr. Kumar has received research support from Neurocrine Biosciences. The institution of Dr. Kumar has received research support from Biovie. The institution of Dr. Kumar has received research support from Neuroderm. The institution of Dr. Kumar has received research support from Sanofi. The institution of Dr. Kumar has received research support from Addex Pharma. The institution of Dr. Kumar has received research support from Integrative Research Laboratories. The institution of Dr. Kumar has received research support from Takeda Pharmaceuticals. The institution of Dr. Kumar has received research support from Neuraly. The institution of Dr. Kumar has received research support from Abbvie. The institution of Dr. Kumar has received research support from Cerevel Therapeutics. The institution of Dr. Kumar has received research support from Transposon Therapeutics. The institution of Dr. Kumar has received research support from Lundbeck. The institution of Dr. Kumar has received research support from Biohaven. The institution of Dr. Kumar has received research support from Revance Therapeutics. The institution of Dr. Kumar has received research support from Impax Laboratories. The institution of Dr. Kumar has received research support from Pharma Two B. The institution of Dr. Kumar has received research support from Enterin. The institution of Dr. Kumar has received research support from CND Life Sciences. The institution of Dr. Kumar has received research support from Neuron23. The institution of Dr. Kumar has received research support from Annexon Biosciences. The institution of Dr. Kumar has received research support from Annovis. The institution of Dr. Kumar has received research support from PTC Therapeutics. The institution of Dr. Kumar has received research support from Uniqure. The institution of Dr. Kumar has received research support from Alexza. The institution of Dr. Kumar has received research support from SparkNeuro. The institution of Dr. Kumar has received research support from Praxis. The institution of Dr. Kumar has received research support from Scion Neurostim. The institution of Dr. Kumar has received research support from Cognition Therapeutics. The institution of Dr. Kumar has received research support from Eli Lilly. Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Medical Director with CenExel RMCR. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as a Managing Member with Research Catalyst, LLC.
David S. Lynch, MBBS, PhD	Dr. Lynch has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vigil Neuroscience. Dr. Lynch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Lynch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vigil Neuroscience.
Jennifer L. Orthmann Murphy, MD, PhD (Hospital of the University of Pennsylvania)	Dr. Orthmann Murphy has received personal compensation in the range of $0-$499 for serving as a Consultant for Vigil Neuroscience. Dr. Orthmann Murphy has received personal compensation in the range of $0-$499 for serving as a Consultant for NovoGlia. 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. The institution of Dr. Orthmann Murphy has received research support from Fishman Family Foundation. The institution of Dr. Orthmann Murphy has received research support from Global Leukodystrophy Initiative Clinical Trial Network. The institution of Dr. Orthmann Murphy has received research support from NINDS. The institution of Dr. Orthmann Murphy has received research support from Montague Investigator Award. Dr. Orthmann Murphy has received personal compensation in the range of $500-$4,999 for serving as a Developing CME content on Neurogenetics with American Neurological Association. Dr. Orthmann Murphy has received personal compensation in the range of $500-$4,999 for serving as a Faculty, Honoraria with CMSC.
Ludger Schols, MD (Eberhard-Karls-University)	Dr. Schols has received personal compensation in the range of $500-$4,999 for serving as a Consultant for VICO Therapeutics. Dr. Schols has received personal compensation in the range of $500-$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.
Nicole Wolf	No disclosure on file
	No disclosure on file
Spyridon Papapetropoulos, MD, PhD (SPIRIDON PAPAPETROPOULOS, MD, PHD)	Dr. Papapetropoulos has received personal compensation for serving as an employee of Vigil Neuroscience . Dr. Papapetropoulos has received personal compensation for serving as an employee of Bionomics Ltd. Dr. Papapetropoulos has received personal compensation in the range of $10,000-$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 Lipocine. Dr. Papapetropoulos has stock in Bionomics Ltd.
Zbigniew K. Wszolek, MD, FAAN (Mayo Clinic- Jacksonville)	Dr. Wszolek has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Polish Neurological Society/Via Medica.