EDIT-B

RNA blood test for bipolar disorder

The challenge

Bipolar disorder is a common mental health condition characterised by recurrent – and in many cases lifelong – mood swings, including manic and depressive episodes. Globally, 45 million people are diagnosed with bipolar disorder[1] but the actual figure of those living with the condition could be much higher.

Worldwide, more than 300 million people are now living with depression.[2] Studies show that up to 40% of patients diagnosed with depression could actually be misdiagnosed and potentially have bipolar disoder.[3] On this basis, bipolar disorder may affect up to 120 million people worldwide.

Bipolar disoder is a chronic disease, which can be managed by the right combination of medication, psychotherapy, psychoeducation, but only if correctly diagnosed. If not well-managed through treatment, bipolar disorder can be debilitating. It can lead to hospitalisation, reduced quality of life, impairment at work, and increased suicide risk.[4] Today, correct diagnosis is challenging because it is limited to clinical evaluation.

Bipolar disorder is often confused with other mental illnesses, notably major depressive disorder. This is because the episodes of mania and hypomania often go unnoticed. Consequently, the average diagnostic delay is of 7.5 years.[5] As bipolar disorder occurs in 70% of cases early in the life of patients (between 16-25 years old), an early diagnosis is crucial to make adequate treatment intervention possible.[6]

Current diagnosis of bipolar disorder consists of a lengthy clinical evaluation comprising a physical exam, mood charting and psychiatric assessment, as well as an analysis of the patients and their family’s medical history. Training and experience of the psychiatrist is of foremost importance for correct evaluation. This can put a strain on health systems which may lack the psychiatric capacity for effective diagnosis.

A lack of diagnosis, delayed diagnosis and misdiagnosis have severe consequences for patients and puts a massive strain on families, close ones and the healthcare system. Medical treatment differs substantially between unipolar depression and bipolar depression, which is why misdiagnosis is particularly problematic. Consequences include greater recurrence of the condition or longer term episodes, impact on work and personal life, increased risk of chronic diseases, and higher mortality.[7][8] Delays in diagnosis also lead to higher health care costs: the societal cost of one-year delay in diagnosis is estimated at €50K per patient in Europe.[9]

The solution

The EDIT-B project team have devloped a new solution to improve the efficiency of the diagnosis of bipolar disorder. It is a blood test, using molecular biology, next-generation sequencing and artificial intelligence allowing a reliable diagnosis. EDIT-B is the first molecular test, based on RNA related biomarkers, which can, from a simple blood draw combined with clinical evaluation, make the differential diagnosis between bipolar disorder and unipolar depression.

The test is highly accurate (>85%) and is carried out on equipment available in most central laboratories.[10] This game-changing innovation has no equivalent on the market, according to market research by Alcediag, the start-up involved in the project. The test is based on their proprietary and patented RNA biomarkers and algorithms, which were developed thanks to the most advanced AI methods (a machine learning approach).

RNA biomarkers are detectable changes in the way genes are expressed in diseases including neuropsychiatric diseases such as bipolar disorder, depression,[11] schizophrenia,[12]and inflammatory ones such as lupus erythematosus.[13] RNA editing is considered as a forward-looking technology.

As a fully biological, accurate test, EDIT-B will change the diagnosis paradigm in psychiatry and reduce the diagnostic delay to a matter of days. This could allow a faster access to the right treatment, reduce avoidable side effects, and completely change the outcome for the patients. Based on the estimated costs of diagnostic delay, the use of EDIT-B will reduce economic burden and optimise use of medical and financial resources, reducing patient hospitalisation and improving health outcomes.

Expected impact

The project team will validate their solution through a clinial trial in Europe and they aim to obtain a CE mark with view to launching EDIT-B in Europe in 2025. Their ultimate goal is to improve care and quality of life of patients with mood disorders across Europe and beyond.

By reducing diagnostic delay, the solution will help people with bipolar disorder to access the right treatment faster, improving their quality of life and ability to manage their condition well. By improving care pathways and access to treatment, this innovative solution has the potential to significantly reduce the economic burden of the bipolar disorder on healthcare systems.

External partners

• GHU Paris Psychiatrie & Neurosciences

References

[1] James, S. L. et al. (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet, 392(10159), 1789-1858.

[2] Institute of Health Metrics and Evaluation. (2022). Global Health Data Exchange (GHDx). [online] Available at: <http://ghdx.healthdata.org/gbd-results-tool?params=gbd-api-2019-permalink/d780dffbe8a381b25e1416884959e88b> [Accessed 9 March 2022].

[3] Angst, J. et al. (2011). Prevalence and characteristics of undiagnosed bipolar disorders in patients with a major depressive episode: the BRIDGE study. Archives of general psychiatry, 68(8), 791-799.

[4] Post, R. M. (2005). The impact of bipolar depression. Journal of Clinical Psychiatry, 66(5), 5-10.

[5] Ghaemi, S. N. et al. (1999). Is bipolar disorder still underdiagnosed? Are antidepressants overutilised? Journal of affective disorders, 52(1-3), 135-144.

[6] Post, R. M. et al. (2008). Incidence of childhood-onset bipolar illness in the USA and Europe. The British Journal of Psychiatry, 192(2), 150-151.

[7] Perlis, R. H. (2005). Misdiagnosis of bipolar disorder. The American journal of managed care, 11(9), 271-274.

[8] Kessing, L. V., & Andersen, P. K. (2017). Evidence for clinical progression of unipolar and bipolar disorders. Acta Psychiatrica Scandinavica, 135(1), 51-64.

[9] World Health Organisation. 2022. [online] Available at: <https://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf> [Accessed 25 March 2022].

[10] Salvetat, N. (2021). A game changer for bipolar disorder diagnosis using RNA editing-based biomarkers. Translational Psychiatry, 89(9) 201.

[11] Chimienti, F. et al. (2019). Brain region-specific alterations of RNA editing in PDE8A mRNA in suicide decedents. Translational psychiatry, 9(1), 1-12.

[12] Kubota-Sakashita, M. et al. (2014). A role of ADAR2 and RNA editing of glutamate receptors in mood disorders and schizophrenia. Molecular brain, 7(1), 1-14.

[13] Wu, J. et al. (2011). FAS mRNA editing in human systemic lupus erythematosus. Human mutation, 32(11), 1268-1277.