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The effect of small molecules on calcium oscillations will be measured using substantially the same method provided in Example 2. To measure primary cortical neuron spontaneous calcium oscillation, rat primary cortical neurons will be prepared. Capsules, tablets, or pills can contain for example the following compounds: microcrystalline cellulose, gum or gelatin as binders; starch or lactose as excipients; stearates as lubricants; various sweetening or flavoring agents. Examples of topical formulations include those in which the oligomer of the invention are in admixture with a topical delivery agent such as lipids, liposomes, fatty acids, fatty acid esters, steroids, chelating agents and surfactants. The formulated drug may comprise pharmaceutically acceptable binding agents and adjuvants. Tau gene was deleted, were used to assess pharmacodynamic endpoints and tissue drug concentrations. Brain tissue (right, frontal cortical region) was collected on dry ice or RNAlater for drug concentration analysis and Tau qPCR respectively at multiple time points following dosing, e.g., 1 week through 16 weeks post-dosing. The maximum time allowed per trial was 60 sec.



For probe trials, the platform was removed and each mouse was allowed to swim for 60 sec. If a mouse was not able to find and mount the platform during 60 sec trial, it was guided to it and allowed to sit for up to 10 sec. Prior to hidden platform training, all mice were exposed to the water maze pool by allowing them to swim down the rectangular channel during 2 pre-training trials. After 60 sec, mice were guided to the platform location before retrieval from the pool. Water maze represents a pool with the diameter of 120 cm. Pharmaceutical compositions and formulations for topical administration can include transdermal patches, ointments, lotions, creams, gels, drops, sprays, suppositories, liquids and powders. The therapeutic molecule formulations can also be emulsions of the active pharmaceutical ingredients and a lipid forming a micellular emulsion. The pharmaceutical compositions of the present invention can be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated.



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