This program will focus on the noninvasive intranasal method of bypassing the blood-brain barrier (BBB) to deliver and target therapeutics to the CNS to treat a variety of disorders. Therapeutics include small molecules, peptides, proteins, oligonucleotides, stem cells and other therapeutic cells. This delivery, targeting and treatment method relies on rapid extracellular delivery along the olfactory and trigeminal neural pathways from the nasal mucosa to the brain and, once inside the brain, on the perivascular pump mechanism of the cerebrovasculature that can rapidly move substances throughout the CNS. Intranasal delivery not only delivers a variety of therapeutics to the CNS but also reduces systemic exposure and unwanted side effects. Different formulations can also be used to facilitate the delivery of poorly water soluble therapeutics, to further reduce systemic exposure to therapeutics and to enhance delivery of therapeutics to the CNS. Nasal drug delivery devices have been developed to facilitate delivery to the upper third of the nasal cavity to enhance delivery of therapeutics to the CNS. Using this method, intranasal therapeutics have been shown to treat stroke, Parkinson disease, Alzheimer disease, brain tumors, multiple sclerosis, and other disorders in animal models. Intranasal insulin has been shown in multiple phase 2 clinical trials to improve memory in both normal adults and in patients with mild cognitive impairment or Alzheimer disease with no change in the blood levels of insulin or glucose. Intranasal delivery is changing the way we treat CNS disorders.