COMPOSITIONS FOR TREATMENT OF SPINAL MUSCULAR ATROPHY

• Main Authors: MARASCO Luciano E, KRAINER Adrian, KORNBLIHTT Alberto R, STIGLIANO Jose
• Format: Patent
• Language: English; Spanish
• Published: 09.06.2023
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

The present disclosure relates compositions and methods to treat neuromuscular diseases and disorders, e.g., spinal muscular atrophy (SMA), characterized by the presence of a splicing silencer located in SMN2 intron 7 pre-mRNA, comprising co-administering a therapeutically effective amount of an antisense oligonucleotide (ASO) complementary to a nucleotide sequence within intron 7 of human SMN2 pre-mRNA; and a subclinical dose of a histone deacetylate inhibitor, e.g., valproic acid, trichostatin A, or a combination thereof. La presente descripción se refiere a composiciones y métodos para tratar enfermedades y trastornos neuromusculares, por ejemplo, la atrofia muscular espinal (SMA), caracterizada por la presencia de un silenciador del corte y empalme ubicado en el pre-ARNm del intrón 7 de SMN2, que comprende coadministrar una cantidad terapéuticamente efectiva de un oligonucleótido de antisentido (ASO) complementario con una secuencia de nucleótidos dentro del intrón 7 del pre-ARNm de SMN2 humano; y una dosis subclínica de un inhibidor de histona desacetilato, por ejemplo, el ácido valproico, tricostatina A o una combinación de los mismos.