Molecular Treatment of Succinic Semialdehyde Dehydrogenase Deficiency with Messenger RNA

Unmet Need: Addressing the Imperative of Succinic Semialdehyde Dehydrogenase Deficiency

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare metabolic disorder caused by mutations in the ALDH5A1 gene. The enzyme plays a crucial role in the breakdown of gamma-aminobutyric acid (GABA). WSU Inventors used ALDH5A1-coding mRNA treatment method to treat patients who are deficient in this enzyme. Inventors proved that human cells isolated from a patient with complete SSADHD are successfully rescued by exposure to a commercially optimized ALDH5A1-coding mRNA.

The Technology: Presented composition and method for treating Succinic Semialdehyde Dehydrogenase Deficiency employing mRNA therapy

The inventors have developed a method of treatment for SSADHD utilizing a codon- optimized, modified mRNA encoding the human succinic semialdehyde dehydrogenase enzyme (hSSADH). Cells transfected with modified hSSADH mRNA express enzymatically-active SSADH protein, resulting in reduced levels of GABA and GHB. ALDH5A1-deficient mice treated with the modified hSSADH mRNA express enzymatically-active SSADH protein in liver and brain.

Applications: