Ceftriaxone has a therapeutic role in Alexander disease

Alexander disease (AD) (MIM 203450) is a rare, usually fatal neurodegenerative disorder, involving primarily astroglial cells in the CNS, caused by dominant mutations in the gene encoding glial fibrillary acidic protein (GFAP) (Brenner et al., 2001). It is characterized by dystrophic astrocytes containing intermediate filament aggregates (Rosenthal fibers) (RFs), in combination with myelin abnormalities (Li et al., 2005). Pathogenetic determinants include a toxic gain-of-function of mutated GFAP which causes aggregates and RFs accumulation in astrocytes and an excitotoxicity related to impairment of the buffering capacity of dystrophic astrocytes and of their ability to metabolize extracellular glutamate ([Mignot et al., 2004] and [Sullivan et al., 2007]). AD remains an untreatable genetic disease that severely limits life expectancy in affected individuals. Here we studied the tolerability and therapeutic effects of the chronic use of cycles of ceftriaxone, a beta-lactam antibiotic with neuroprotective effects (Rothstein et al., 2005), in a patient affected by adult AD with a rapidly progressive clinical course. Because AD is rare and its presentation varies it is difficult to evaluate treatments in controlled trials, thus prolonged, longitudinal single-patient studies may be a useful approach to identify the new utilization of drugs in this pathology. The successful clinical outcome related to ceftriaxone reported here in a patient with adult AD highlights the possibility that this β-lactam antibiotic may be useful for other AD patients and, possibly, for other neurodegenerative disorders with astrocyte involvement.