METHODS AND KITS FOR TREATING AND CLASSIFYING INDIVIDUALS

摘要

The present disclosure provides methods and kits for treating and classifying individuals at risk of or suffering from a neurological and/or mitochondrial dysfunction or disorder. In general, the individuals are treated and/or classified based on the presence of a loss-of-function mutation in nuclear DNA encoding one or more proteins selected from the group consisting of ALDH1L1, ALDH1L2, FOLR1, FPGS, GCSH, GLDC, MTHFD1, MTHFD1L, MTHFD2, MTHFD2L, MTHFS, MTRR, SHMT1, SHMT2 and SLC25A32. Treatment involves the administration of a therapeutically effective amount of folinic acid, glycine or a pharmaceutically acceptable salt thereof.

主权项

1. A method of treating an individual at risk of or suffering from a mitochondrial dysfunction or disorder, autism, and/or Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), the method comprising administering to the individual a therapeutically effective amount of folinic acid, glycine or a pharmaceutically acceptable salt thereof, wherein DNA of the individual encoding one or more proteins selected from the group consisting of aldehyde dehydrogenase 1 family, member L1 (ALDH1L1), aldehyde dehydrogenase 1 family, member L2 (ALDH1L2), folate receptor 1 (FOLR1), folylpolyglutamate synthase (FPGS), glycine cleavage system H protein (GCSH), glycine cleavage system P protein (GLDC), C-1-tetrahydrofolate synthase (cytoplasmic) (MTHFD1), monofunctional C1-tetrahydrofolate synthase, mitochondrial (MTHFD1L), bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2), methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2-like (MTHFD2L), 5,10-methenyltetrahydrofolate synthetase (MTHFS), methionine synthase reductase (MTRR), serine hydroxymethyltransferase 1 (SHMT1), serine hydroxymethyltransferase 2 (SHMT2) and solute carrier family 25 (mitochondrial folate carrier) (SLC25A32) includes a loss-of-function mutation.