Grant Awarded

Autologous Stem Cell Therapy for ALS
Martin, Lee, PhD
Johns Hopkins School of Medicine, Baltimore, Maryland

Motor neurons (MN) in patients with amyotrophic lateral sclerosis (ALS) are selectively depleted, resulting in paralysis and death. Neuronal replacement by stem cell therapy offers new hope for treating ALS. We have identified a new and plentiful source of multipotent neural stem cells (NSC) in the adult mammalian brain, specifically in the olfactory bulb (OB). These NSC have the capacity to become MN. We propose to use adult OB-NSC for autologous neuronal replacement therapy in a mouse model of familial ALS. First, we will determine if adult presymptomatic and symptomatic transgenic mice (G93A) with mutant human superoxide dismutase-1 have a normal complement of NSC in the OB using cell proliferation and NSC markers and stereological counting of NSC number. Second, we will determine if OB-derived NSC in ALS mice can be cultured and stimulated to proliferate and differentiate into MN. Third, OB-NSC will be used for autologous replacement/rescue of spinal MN in presymptomatic and early symptomatic ALS mice. Our proposal is important to ALS because we will be the first to attempt to harness a new source of non-embryonic NSC from the adult brain as a novel autologous cell therapy for the treatment of ALS in an animal model.