Developing small molecules as a neurosteroid replacement strategy for treating postpartum psychosis

This project has the potential to ultimately deliver significant patient impact in the relatively neglected area of maternal mental health.

In the short term, the funding requested will be used to identify a novel, brain penetrant synthetic neuroactive steroid that will be a low efficacy positive allosteric modulator (PAM) of GABAARs but, importantly, will have a reduced intrinsic efficacy relative to endogenous neurosteroids, the prototypic example of which is allopregnanolone.

Such a low efficacy PAM compound is anticipated to maintain mood stabilising efficacy but have a much improved safety profile (i.e., reduced sedation or unconsciousness) relative to high efficacy PAMs.

If successful, this project will then form the platform to secure further funding for the additional preclinical drug discovery and development activities required to identify a first-in-human-ready drug.

At that point, we will seek additional, commercial funding (either by partnering with a pharma company or securing VC investment to form a spin-out company) that will enable the clinical development of a novel, first-in-class drug for the treatment of the symptoms of postpartum psychosis and has a safety profile suitable for the prophylactic treatment of women at-risk.