Pexidartinib treatment in Alexander disease model mice reduces macrophage numbers and increases glial fibrillary acidic protein levels, yet has minimal impact on other disease phenotypes.

BACKGROUND: Alexander disease (AxD) is a rare neurodegenerative disorder that is caused by dominant mutations in the gene encoding glial fibrillary acidic protein (GFAP), an intermediate filament that is primarily expressed by astrocytes. In AxD, mutant GFAP in combination with increased GFAP expression result in astrocyte dysfunction and the accumulation of Rosenthal fibers. A neuroinflammatory environment consisting primarily of macrophage lineage cells has been observed in AxD patients and mouse models. METHODS: To examine if macrophage lineage cells could serve as a therapeutic target in AxD, GFAP knock-in mutant AxD model mice were treated with a colony-stimulating factor 1 receptor (CSF1R) inhibitor, pexidartinib. The effects of pexidartinib treatment on disease phenotypes were assessed. RESULTS: In AxD model mice, pexidartinib administration depleted macrophages in the CNS and caused elevation of GFAP transcript and protein levels with minimal impacts on other phenotypes including body weight, stress response activation, chemokine/cytokine expression, and T cell infiltration. CONCLUSIONS: Together, these results highlight the complicated role that macrophages can play in neurological diseases and do not support the use of pexidartinib as a therapy for AxD.

Effects of assistance dogs on persons with mobility or hearing impairments: a pilot study.

Service dogs help persons with mobility impairments by retrieving items and performing other tasks. Hearing dogs alert persons with hearing impairments to environmental sounds. We conducted a pre-post, wait list-controlled pilot study to assess the impact of the dogs on the lives of recipients. Participants were recruited through two assistance dog training organizations and completed an initial questionnaire packet. The Experimental group completed another packet 6 months after receiving a dog. The Control group completed a second packet 6 months after the initial data collection. On average, dog recipients were very satisfied with their assistance dogs. Both service and hearing dog recipients reduced their dependence on other persons. Service dog recipients reduced hours of paid assistance. No other significant change occurred in various standardized outcome measures. Assistance dogs had a major positive impact on the lives of recipients. More appropriate measurement instruments are needed to capture the impact of these dogs.