DM1, an unmet genetic disease
ATX-01 consists of an RNA oligonucleotide that targets and blocks the miR-23b, upregulated in DM1 muscle tissues. Thus, ATX-01 is an antimiR that targets critical pathways leading to disease through a first-in-class mechanism of action.
DM1 is caused by an abnormal expansion of a trinucleotide repeat in a non-coding region of the DMPK gene. After transcription, mutated DMPK mRNA folds into a hairpin that sequesters MBNL1 proteins, causing a lack of function of these proteins that is directly related to the symptoms in the patients, mainly muscle atrophy and wasting.
While other approaches target the toxic mRNA of DMPK that accumulates as ribonuclear foci inside the nuclei, ATX-01 increases the levels of available MBNL, the protein directly related to the disease symptoms, by inhibiting miR-23b that is upregulated in the cytoplasm.
In the DM1 mouse model, HSALR, ATX-01 acts as a disease modifier therapy, increasing MBNL protein levels and reversing the disease phenotype. Now, ATX-01 may provide new hope for patients suffering from DM1