Intranasal Delivery of Peptide Drugs to the Brain

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DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a progressive and fatal neurological disorder that affects approximately one-tenth of the population over the age of 65. There is currently no cure for the disease. The pathological hallmarks of the disease include the formation and accumulation in the brain of ß-amyloid (Aß), widely recognized to be the major neurotoxic agent in AD. Earlier therapeutic attempts at lowering total Aß production were unsatisfactory as they directly targeted the catalytic activities of ß- or γ-secretase, enzymes known to hydrolyze other substrates as well as APP, many with critical cellular functions. New therapeutic approaches that can inhibit total Aß production without targeting the activities of th ß- or the γ-secretase are therefore of great interest. We have a novel technology that does not target the secretases, which has yielded a potential peptide drug candidate, P8, with the ability to inhibit the production of Aß in vitro and in a Tg mouse model of AD, which is stable and which can be delivered to the brain. We are now developing P8 as a new peptide drug for the treatment of AD. Importantly, Cenna's peptide-induced reductions of total Aß and Aß40 and 42, do not modify or inhibit either ß- or γ-secretase activities. Studies carried out in the Phase SBIR project showed that P8 can be delivered to the brain both, by intranasal and intravenous administration. In this Phase 2 application we propose to carry out studies for the pre-clinical development of P8. Studies will include the characterization of P8, the development of a pre-formulation to support intranasal delivery of P8 in pre-clinical studies, the pharmacokinetic ADME evaluation of P8 and the development of pre-clinical pharmacology/efficacy of P8.