Abstract: Probiotic bacteria are genetically modified to produce and excrete enhanced levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Exemplary probiotic bacteria include Lactococcus lactis (L. lactis). The genetically modified probiotic bacteria can be prepared as an aqueous suspension and/or incorporated into food and nutraceuticals for oral administration to a subject. An oral formulation including the genetically modified probiotic bacteria can be used to treat inflammatory diseases and/or behavioral disorders caused by or associated with GABA-GABA signaling deficiency or by excess of excitatory neurotransmitters (such as glutamate). Inflammatory conditions that can be treated with the genetically modified probiotic bacteria include multiple sclerosis (MS) and irritable bowel disease (IBD).

Abstract: Provided herein are compositions and methods for treating succinic semialdehyde dehydrogenase deficiency (SSADHD). Compositions may include a gene encoding a functional succinic semialdehyde dehydrogenase (SSADH) enzyme, such as ALDH5A1, operably linked to a targeting vector. The functional SSADII enzyme is envisioned to lower the levels of circulating gamma-hydroxybutyric acid (GHB) and ?-aminobutyric acid (GABA). In some embodiments, combination therapies are envisioned, comprising administering to the subject therapeutically effective amounts of a combination of a composition comprising a gene encoding a functional SSADII enzyme operably linked to a targeting vector; one or more mTOR inhibitors; and a GABA-T inhibitor. Suitable mTOR inhibitors include rapamycin, while suitable GABA-T inhibitors include vigabatrin.

Abstract: Provided herein are compositions and methods for treating succinic semialdehyde dehydrogenase deficiency (SSADHD). Compositions may include a gene encoding a functional succinic semialdehyde dehydrogenase (SSADH) enzyme, such as ALDH5A1, operably linked to a targeting vector. The functional SSADH enzyme is envisioned to lower the levels of circulating gamma-hydroxybutyric acid (GHB) and ?-aminobutyric acid (GABA). In some embodiments, combination therapies are envisioned, comprising administering to the subject therapeutically effective amounts of a combination of a composition comprising a gene encoding a functional SSADH enzyme operably linked to a targeting vector; one or more mTOR inhibitors; and a GABA-T inhibitor. Suitable mTOR inhibitors include rapamycin, while suitable GABA-T inhibitors include vigabatrin.