Histone Deacetylases (HDACs) are a family of enzymes that mediate transcriptional repression of many genes, by inducing chromatin relaxation making gene sequences accessible for transcription. This family of enzymes have pleiotropic functions. In particular, inhibition of the HDAC2 isoform has been strongly related with synapse regrowth, immune suppression and expression of genes relevant for synaptopathies and neurodegenerative diseases.
MBF-015 has been designed as a potent CoREST/HDAC1/2 inhibitor for the treatment of synaptopathies. It is a small molecule which freely crosses the blood-brain barrier and penetrates the brain. The compound has demonstrated significant induction of synaptic regrowth in animal models. It also showed a strong PK-PD relation in the EAE immunosuppression model. It is therefore a good candidate for the treatment of synaptopathies.
MBF-015 has completed IND-enabling pre-clinical development, showing it is well-tolerated and with no genotoxic potential. It has a broad therapeutic window.
MBF-015 is currently completing Phase I evaluation in healthy volunteers, prior to initiating a phase IIa proof-of-concept trial in Huntington’s Disease patients later in 2023.
The patent protecting MBF-015 has been granted in the US and EU and is wholly owned by Medibiofarma.