Abstract: Fragile X syndrome (FXS) is the most common inherited form of human intellectual disability. FXS is caused by loss of function of the FMR1 gene which results in significant behavioral deficits in spatial learning and memory tests. FMR1?/? knockout mice share many of the learning deficits and decreased synaptic function encountered in FXS patients. Anecdotal evidence indicates a reduction in the amount of Reelin, a large extracellular signaling protein important for normal hippocampal synaptic plasticity, may play role in the etiology of FXS. Disclosed herein is a rAAV9 Reelin viral vector expressing a REELIN repeat R3+R6 fusion protein that is shown to rescue cognitive deficits in FMR1?/? mice as evaluated in the Hidden Platform Water Maze, Open Field and Fear Conditioning. Reelin gene therapy is therefore potentially a novel therapeutic for the treatment of Fragile X Syndrome.

Abstract: One aspect described herein relates to a recombinant adeno-associated virus (rAAV) vector and a method for use thereof or treating Angelman Syndrome. Another aspect described herein is a UBE3A rAAV vector and method for use thereof for treating a UBE3A deficiency, e.g. Angelman syndrome, in humans.

Abstract: Disclosed are methods of influencing, and enhancing, cognitive function and memory by increasing, and/or preventing interference with, Reelin levels as well as Reelin signaling. Cognitive function is improved, in a subject in need thereof, by administering a therapeutically effective amount of Reelin, a Reelin-specific modulator or an agonist of a lipoprotein receptor to the subject. The lipoprotein receptor can be selected from candidates such as ApoER2 and VLDLR. As disclosed herein, agonists of the lipoprotein receptor for use with the inventive method include APC, Sep and Fc-RAP. In addition to administering exogenous Reelin, a Reelin-specific modulator, such as a recombinant Reelin fragment, can be used to increase Reelin levels and/or signaling.

Abstract: Disclosed are methods of influencing, and enhancing, cognitive function and memory by increasing, and/or preventing interference with, Reelin levels as well as Reelin signaling. Cognitive function is improved, in a subject in need thereof, by administering a therapeutically effective amount of Reelin, a Reelin-specific modulator or an agonist of a lipoprotein receptor to the subject. The lipoprotein receptor can be selected from candidates such as ApoER2 and VLDLR. As disclosed herein, agonists of the lipoprotein receptor for use with the inventive method include APC, Sep and Fc-RAP. In addition to administering exogenous Reelin, a Reelin-specific modulator, such as a recombinant Reelin fragment, can be used to increase Reelin levels and/or signaling.

Abstract: Disclosed are methods of influencing, and enhancing, cognitive function by increasing, and/or preventing interference with, Reelin levels as well as Reelin signaling. Cognitive function is improved, in a subject in need thereof, by administering a therapeutically effective amount of Reelin, a Reelin-specific modulator or an agonist of a lipoprotein receptor to the subject. The lipoprotein receptor can be selected from candidates such as ApoER2 and VLDLR. As disclosed herein, agonists of the lipoprotein receptor for use with the inventive method include APC, Sep and Fc-RAP. In addition to administering exogenous Reelin, a Reelin-specific modulator, such as a recombinant Reelin fragment, can be used to increase Reelin levels and/or signaling.

Abstract: Disclosed are methods of influencing, and enhancing, cognitive function by increasing, and/or preventing interference with, Reelin levels as well as Reelin signaling. Cognitive function is improved, in a subject in need thereof, by administering a therapeutically effective amount of Reelin, a Reelin-specific modulator or an agonist of a lipoprotein receptor to the subject. The lipoprotein receptor can be selected from candidates such as ApoER2 and VLDLR. As disclosed herein, agonists of the lipoprotein receptor for use with the inventive method include APC, Sep and Fc-RAP. In addition to administering exogenous Reelin, a Reelin-specific modulator, such as a recombinant Reelin fragment, can be used to increase Reelin levels and/or signaling.

Abstract: Disclosed are methods of influencing, and enhancing, cognitive function by increasing, and/or preventing interference with, Reelin levels as well as Reelin signaling. Cognitive function is improved, in a subject in need thereof, by administering a therapeutically effective amount of Reelin, a Reelin-specific modulator or an agonist of a lipoprotein receptor to the subject. The lipoprotein receptor can be selected from candidates such as ApoER2 and VLDLR. As disclosed herein, agonists of the lipoprotein receptor for use with the inventive method include APC, Sep and Fc-RAP. In addition to administering exogenous Reelin, a Reelin-specific modulator, such as a recombinant Reelin fragment, can be used to increase Reelin levels and/or signaling.

Abstract: An implantable neuronal prosthetic and method of manufacture thereof includes at least one elongated electrode shank adapted for arrangement in the brain having at least one electrode contact disposed on its surface and arranged to electrically couple with said brain. The at least one elongated electrode shank is formed form a single crystal cubic silicon carbide. An insulation layer of amorphous, polycrystalline, or single crystal silicon carbide is disposed over the elongated electrode shank; the insulation layer of amorphous, polycrystalline, or single crystal silicon carbide is removed from the at least one electrode contact. Signal control electronics are attached to the at least one elongated electrode shank and are in electrical communication with the at least one electrode contact. In an embodiment, a plurality of the at least one elongated electrode shanks are arranged into a matrix.

Abstract: The microfabricated prosthetic device uses local, direct, and wavelength-specific optical stimulation to achieve an action potential from a single or small group of neurons within the central nervous system (CNS). The device is biocompatible, mechanically flexible, and optically transparent. The device can also use integrated electrodes for additional input/output (IO) locations, signal verification, feedback, wireless communication, and characterization of the electrochemically-evoked potential received from the activated neuron. The purpose of the device is to act as a neural interface prosthetic. The prosthetic is designed as the central component of a brain machine interface (BMI).

Abstract: An implantable neuronal prosthetic and method of manufacture thereof includes at least one elongated electrode shank adapted for arrangement in the brain having at least one electrode contact disposed on its surface and arranged to electrically couple with said brain. The at least one elongated electrode shank is formed form a single crystal cubic silicon carbide. An insulation layer of amorphous, polycrystalline, or single crystal silicon carbide is disposed over the elongated electrode shank; the insulation layer of amorphous, polycrystalline, or single crystal silicon carbide is removed from the at least one electrode contact. Signal control electronics are attached to the at least one elongated electrode shank and are in electrical communication with the at least one electrode contact. In an embodiment, a plurality of the at least one elongated electrode shanks are arranged into a matrix.

Abstract: Disclosed are methods of influencing, and enhancing, cognitive function by increasing, and/or preventing interference with, Reelin levels as well as Reelin signaling. Cognitive function is improved, in a subject in need thereof, by administering a therapeutically effective amount of Reelin, a Reelin-specific modulator or an agonist of a lipoprotein receptor to the subject. The lipoprotein receptor can be selected from candidates such as ApoER2 and VLDLR. As disclosed herein, agonists of the lipoprotein receptor for use with the inventive method include APC, Sep and Fc-RAP. In addition to administering exogenous Reelin, a Reelin-specific modulator, such as a recombinant Reelin fragment, can be used to increase Reelin levels and/or signaling.