Target validation in psychiatry: addressing unmet therapeutic needs

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The Psychiatry Consortium and the British Neuroscience Association recently published their ‘Guiding Principles for Robust Target Validation in Psychiatry’. Dr Ekta Patel, Psychiatry Consortium Partnership Manager, spoke to DDW’s Diana Spencer about how the guide can help researchers to create a target validation package and the need for new therapeutic targets in this underfunded specialty. 

DS: Please can you tell me a bit more about the role and purpose of the Psychiatry Consortium?  

EP: The Psychiatry Consortium, launched in 2019, is a strategic collaboration of leading medical research charities and pharmaceutical companies focusing on the challenge of identifying and validating novel drug targets to address the unmet therapeutic needs of people living with mental health conditions. 

The Psychiatry Consortium Partners act as a syndicate – collectively sharing the funding of, and therefore the risk associated with, drug discovery. We provide opportunities for funding, collaboration and industry know-how in this area of unmet patient need. 

DS: Why was there a need for ‘Guiding Principles for Robust Target Validation in Psychiatry’, and who was involved in the workshop that led to its creation?  

EP: We strive to bring all aspects of the global research community together to tackle and address key challenges within drug discovery. In July 2022, we convened a group of drug discovery experts, comprising Psychiatry Consortium Industry Partners, members of the British Neuroscience Association and representatives from academic institutions to discuss the approaches and considerations for target validation projects.  

This discussion formed the basis of the ‘Guiding Principles for Robust Target Validation in Psychiatry’1 and is intended to highlight key considerations deemed important by the drug discovery community when building a target validation package for novel therapeutic targets. We hope the guidance will support applicants in building projects that address gaps in our knowledge and strengthen the body of evidence to support a target’s role in a particular disease or condition and/or its potential as a therapeutic target. 

DS: The document states there is a “paucity of new targets in psychiatric medicines research”. Why do you think that is?  

EP: While we are improving our knowledge of disease biology, there has always been a relatively poor understanding of the brain and brain dysfunction associated with disorders. When we don’t fully understand how different brain circuits are affected in mental health conditions, it’s difficult to know how to modulate them for therapeutic gain. A deep understanding of a disease or condition and its causative molecular mechanisms will help identify novel targets.  

In addition, mental health research is drastically underfunded, both in terms of the burden of mental illness and in comparison, to physical health conditions – just £9 per year is spent on mental health research for each person affected by mental illness the UK2. 

DS: What do you think are currently the greatest unmet therapeutic needs of people living with mental health conditions?  

EP: The scale and impact of mental illness across society are immense. In 2019, one in every eight people, or 970 million people worldwide, were living with a mental illness – with anxiety and depressive disorders the most common3. In 2020, the number of people living with anxiety and depressive disorders rose significantly because of the Covid-19 pandemic. Initial estimates show a 26% and 28% increase, respectively, for anxiety and major depressive disorders in just one year4. Whilst we have treatments for some mental health disorders, they don’t work for everyone, and side effects can be difficult to tolerate. Drug discovery in this field has stayed relatively stagnant compared to other therapeutic areas, with no new types of medicines coming forward in the last ~30 years. We need to explore new biology to unlock new potential treatment targets and broaden the treatment options for people living with mental health conditions.    

DS: What would be your top tips to researchers to help them create a target validation proposal that will attract industry funding? 

EP: Be sure that there is a clear understanding and evidence of the link between the target and neural circuit, pathway, or mechanism. The proposal should also have a sound therapeutic hypothesis of how modulation of the target may have a therapeutic effect. 

Ultimately having converging lines of evidence significantly increases confidence in a proposal. Our guiding principles document outlines how to address gaps in knowledge and strengthen the body of evidence to support a target’s role in a particular disease or condition. It is a great read for those looking to submit a proposal for industry collaboration and funding.  

DS: What might make a target less attractive for industry investment? 

EP: It is important to note that there are no common criteria across the industry. Each company will have different perceptions of what makes a target attractive for investment. However, targets deemed intractable, or those with previous clinical failures may be unattractive for investment. Where targets are broadly expressed outside of the CNS or are known to be involved in critical cellular processes, safety concerns may also make the target less attractive. 

DS: Do you have funding available at the moment? 

EP: The Psychiatry Consortium is currently accepting applications until December 5, 2022. We are seeking project proposals that focus on the validation of novel molecular drug targets for mental health conditions. To find out more about what we are looking for, companies can visit our website at psychiatryconsortium.org, which includes helpful resources for support. We also have a Frequently Asked Questions page which may clarify some common queries about the funding mechanism of the Psychiatry Consortium.   

DS: Is there a role for patients in these early stages of drug discovery? 

EP: While patients are usually involved at the stage of clinical trial execution, having a ‘seat at the table’ for patient representatives during the early stages of clinical trial design is fundamental to understanding the patient’s needs. We are currently working with our charity partners to bring the patient voice into our early drug discovery discussions. 

References 

  1. Psychiatry Consortium and BNA. Guiding Principles for Robust Target Validation in Psychiatry https://psychiatryconsortium.org/wp-content/uploads/2022/09/Guiding-Principles-for-Robust-Target-Validation-in-Psychiatry-v2.pdf  
  2. MQ. UK Mental Health Research Funding 2014-17 https://www.mqmentalhealth.org/wp-content/uploads/UKMentalHealthResearchFunding2014-2017digital.pdf  
  3. Institute of Health Metrics and Evaluation. Global Health Data Exchange (GHDx) https://vizhub.healthdata.org/gbd-results/   
  4. WHO. Mental Health and COVID-19: Early evidence of the pandemic’s impact https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Mental_health-2022.1  

 Biography 

Ekta PatelDr Ekta Patel is a translational scientist with over eight years of drug discovery research experience in both academic and industrial roles. Combining her scientific knowledge and experience of working across SMEs, academic research groups and pharmaceutical companies, Ekta provides in-depth support to our collaborators to develop and deliver a portfolio of projects. Alongside her role at the Psychiatry Consortium, Ekta is a member of the Greater Manchester HRA Research Ethics Committee and is a strong advocate of patient involvement throughout the drug discovery process. 

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