HUSH, NEXT PROMPT: Epigenetics and the Nuclear RNA Exosome in Human Aging and Disease.

Colony-stimulating factor 1 receptor–related disorder (CSF1R-RD) is a rare hereditary neurodegenerative condition caused by pathogenic variants in the gene [,]. CSF1R-RD is typically a rapidly progressive disorder with an average onset in a patient’s 40s and a mean survival of approximately 6.8 years [-]. Clinically, it presents with a combination of cognitive decline, behavioral and psychiatric symptoms, and motor disturbances. Symptoms usually progress rapidly, leading to severe disability, increased care needs, and premature death [,,,]. The most widely recognized therapeutic intervention to date is hematopoietic stem cell transplantation (HSCT). Two recent studies have demonstrated the potential of HSCT to halt disease progression. Yska et al. [] reported outcomes in an international cohort of 17 patients, observing clinical improvement in more than 50% of the patients at 12 months post-intervention and stabilization in an additional 25%. Similarly, Wu et al. [] reported motor improvement and cognitive stabilization in a cohort of 8 patients from China. A 2021 US cohort also showed neurological stabilization in 6 out of 7 patients who underwent HSCT []. Although these findings are encouraging, long-term data and comparisons with the natural history of untreated CSF1R-RD are lacking. To address this knowledge gap, we present an extended cohort of patients with CSF1R-RD, including individuals from previously published studies [-]. This report represents the first observational, matched-control study to employ a unified clinical and radiological assessment, enabling the evaluation of long-term outcomes in patients with CSF1R-RD and their individual clinical trajectories before and after HSCT.