Treatment of CSF1R-Related Leukoencephalopathy: Breaking New Ground

Philip W. Tipton, Daniel Kenney-Jung, Beth K. Rush, Erik H. Middlebrooks, David Nascene, Balvindar Singh, Shernan Holtan, Ernesto Ayala, Daniel F. Broderick, Troy Lund, Zbigniew K. Wszolek

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25 Scopus citations


BACKGROUND: Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease-modifying treatment.

OBJECTIVE: The objective of this study was to determine the effect of HSCT on disease progression.

METHODS: We collected all available clinical data from a cohort of 7 patients with CSF1R-related leukoencephalopathy who underwent HSCT at our institutions. Clinical data included detailed neurological examination by a board-certified neurologist, serial cognitive screens, formal neuropsychological evaluations, and serial brain magnetic resonance imaging (MRI).

RESULTS: Our patients had an average disease duration of 27.6 months at the time of transplant, and we have 87 months of total posttransplant follow-up time (median, 11; range, 2-27). One patient died in the periprocedural period. The remaining patients showed a variable response to treatment, with 6 of 7 patients trending toward stabilization on motor examination, cognitive scores, and/or MRI abnormalities, especially with white matter lesion burden.

CONCLUSIONS: This is the largest series of patients with CSF1R-related leukoencephalopathy receiving HSCT. We conclude that HSCT can stabilize the disease in some patients. Variability in patient responsiveness suggests that measures of disease heterogeneity and severity need to be considered when evaluating a patient's candidacy for transplant. HSCT appears to be the first disease-modifying therapy for CSF1R-related leukoencephalopathy. This milestone may serve as a foothold toward better understanding the disease's pathomechanism, thus providing new opportunities for better disease-specific therapies. © 2021 International Parkinson and Movement Disorder Society.

Original languageEnglish (US)
Pages (from-to)2901-2909
Number of pages9
JournalMovement Disorders
Issue number12
Early online dateJul 30 2021
StatePublished - Dec 2021

Bibliographical note

Funding Information:
Philip W. Tipton reports no disclosures. Daniel Kenney‐Jung is partially supported by grants from the Rare Disease Foundation and CFC International and is a Co‐I on Bluebird Pharmaceuticals (ALD‐102, ALD‐103, ALD‐104). Beth K. Rush reports no disclosures. Erik H. Middlebrooks receives research support from Mayo Clinic Focused Team Research Program, Mayo Clinic Research Accelerator for Clinicians Engaged in Research Program, Boston Scientific Corp, Varian Medical Systems, Inc., and the National Institutes of Health (R33‐CA240181). He is also consultant for Boston Scientific Corp. David Nascene is consultant for Biogen and World Care Clinical. Balvindar Singh reports no disclosures. Shernan Holtan provided consulting services to Incyte and Generon, neither of which is relevant to this report. Ernesto Ayala reports no disclosures. Daniel F. Broderick reports no disclosures. Troy Lund reports no disclosures. Zbigniew K. Wszolek is partially supported by the Mayo Clinic Center for Regenerative Medicine, Mayo Clinic in Florida Focused Research Team Program, the gifts from The Sol Goldman Charitable Trust, the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and the Albertson Parkinson's Research Foundation. He serves as PI or Co‐PI on Biogen, Inc. (228PD201), Biohaven Pharmaceuticals, Inc. (BHV4157‐206 and BHV3241‐301), and Neuraly, Inc. (NLY01‐PD‐1) grants. He serves as Co‐PI of the Mayo Clinic APDA Center for Advanced Research. This project is partially supported by the Mayo Clinic in Florida Focused Research Team Program. Relevant conflicts of interest/financial disclosures:

Publisher Copyright:
© 2021 International Parkinson and Movement Disorder Society


  • CSF1R-related leukoencephalopathy
  • microglia
  • transplant


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