DDW’s Diana Spencer provides an overview of the latest innovations in drug discovery for mental health.
World Wellbeing Week was created to celebrate the many aspects of wellbeing, from meaningful, purposeful work to financial security, physical, mental and emotional health, social resilience and empathic corporate and civic leadership, community relations and care for the environment.
To mark the occasion, this article summarises the most recent news about the ways drug discovery is improving wellbeing and mental health through innovative new treatments and therapies.
There has been growing interest in the therapeutic potential of psychedelic drugs for conditions such as depression, post-traumatic stress disorder and substance use disorders.
The potential of psychedelic drugs is covered in this In Conversation With podcast, in which DDW’s Megan Thomas speaks with Dr Mark Varney, the Chief Scientific Officer at PsychoGenics.
Recently, the US Food and Drug Administration (FDA) published new draft guidance to highlight fundamental considerations to researchers investigating the use of psychedelic drugs.
Designing clinical studies to evaluate the safety and effectiveness of these compounds presents a number of unique challenges that require careful consideration.
Elevating extracellular serotonin
In 2023, Evecxia Therapeutics reported favourable safety, tolerability, pharmacokinetic, and pharmacodynamic data from a Phase I trial of EVX-101 in healthy volunteers treated with escitalopram.
EVX-101 is a sustained-release tablet formulation of 5-hydroxytryptophan (5-HTP), the natural precursor to serotonin, and low-dose carbidopa. Administered with a first-line antidepressant, the drug is intended to elevate extracellular serotonin beyond the first-line antidepressant effect to augment antidepressant efficacy.
Precision medicines in major depressive disorder
A Phase IIa study of Alto Neuroscience’s ALTO-100 has demonstrated clear evidence of efficacy and a favourable safety record in patients with major depressive disorder (MDD).
In the study, patients with a biomarker profile that ties back to a mechanistic understanding of ALTO-100 and depression exhibited a significantly greater change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores and response rates than those without the biomarker profile.
The Phase II study used Alto’s Precision Psychiatry Platform to identify likely drug responders based on an understanding of biological heterogeneity in depression and ALTO-100’s novel mechanism.
Better drugs for anxiety
Anxiety disorders are common, but the efficacy of currently available anti-anxiety drugs is low.
A team of scientists at the Universities of Bristol and Exeter in the UK has discovered that modification of a gene in the brain can reduce anxiety levels.
The researchers showed that miR-483-5p acts as a molecular brake that offsets stress-induced amygdala changes to promote anxiety relief – the first step towards the discovery of novel, more potent and much-needed treatments for anxiety disorders that will enhance this pathway.
Neurosteroids for anxiety and postpartum depression
PureTech Health has launched a clinical trial of its therapeutic candidate LYT-300 (oral allopregnanolone) for the potential treatment of anxiety disorders and postpartum depression (PPD).
The Phase IIa proof-of-concept trial will evaluate short-term changes in anxiety-related patient reported outcomes in approximately 50 healthy volunteers. Another Phase IIa trial will evaluate LYT-300 in patients with moderate to severe PPD.
Results from a Phase I trial showed that oral administration of LYT-300 achieved blood levels of allopregnanolone at or above those associated with therapeutic benefit in PPD and ninefold greater than orally administered allopregnanolone.
Diagnosis using artificial intelligence
Pangaea Data is a provider of an artificial intelligence (AI)-driven product for characterising patients by automatically discovering clinical signatures for hard-to-diagnose conditions.
In early June 2023 the company was awarded a strategic partnership by the Mental Health Research for Innovation Centre (M-RIC).
M-RIC will be applying Pangaea’s product to characterise patients across hard-to-diagnose mental health conditions and discover new clinically actionable intelligence, which will help to find more undiagnosed, misdiagnosed and miscoded patients.