NEW YORK – French diagnostics company Alcediag has together with partners developed a blood-based test for bipolar disorder that it plans to offer clinically in the fall. The Montpellier-based firm described the six-biomarker test in a recent paper in the journal Translational Psychiatry, and intends to launch the assay in October. It also recently obtained a CE-IVD mark for the test, called Edit-B.
Dinah Weissmann, Alcediag's general manager, said in an interview this week that the company obtained a CE-IVD mark for Edit-B under the In Vitro Diagnostic Directive, which was in effect until May 26, when Europe's new In Vitro Diagnostic Regulation began to apply.
The test's certificate will remain valid through May 2026 as Europe transitions to the new regulation though, by which time Alcediag intends to obtain a CE mark under the IVDR.
Alcediag was founded in 2014 and is a subsidiary of French diversified technologies firm Alcen. The firm currently has a team of 15 employees at sites in Montpellier and in Paris. According to Weissmann, Alcediag is exploring the option of offering the test as a service via a CLIA-compliant partner laboratory in the US sometime next year. Alcediag has also begun to engage the US Food and Drug Administration regarding a potential submission of Edit-B to the agency. Weissmann estimated the firm might submit the test to the FDA in two to three years.
Alcediag's goal is to deliver a test to market that will disrupt the conventional trial-and-error approach used by psychiatrists to diagnose bipolar disorder, a process that can take several years. "Our blood test takes a few days to produce a result, and will change the lives of patients," Weissmann said.
To develop Edit-B, Alcediag worked with partners at Montpellier University Hospital; Les Toises Psychiatry Centre in Lausanne, Switzerland; and the University of Pittsburgh. The Translational Psychiatry study involved a discovery cohort of 57 patients who underwent adenosine-to-inosine RNA editome — the part of the genome that has been edited — analysis following whole-transcriptome sequencing on the Illumina NextSeq 500.
They found 646 variants in 366 genes that were differentially edited between depressed patients and health volunteers. Following additional analysis, Alcediag and partners selected eight candidate biomarkers that they tested in a validation cohort of 410 participants using multiplexed targeted sequencing. They combined these markers with a machine-learning approach and developed a subset of six RNA editing-related markers that they claim can differentiate patients with depression from those with bipolar disorder.
"With eight biomarkers we were able to discriminate depressed patients from controls," Weissmann commented. "After that, we wanted to see if we were able to discriminate between unipolar and bipolar disorder in depressed patients. To do that, we need only six biomarkers."
As noted in the paper, the six genes selected are calcium/calmodulin-dependent protein kinase type 1D (CAMK1D); growth factor receptor bound protein 2-associated protein 2 (GAB2); interferon alpha/beta receptor 1 (IFNAR1); ATP-sensitive inward rectifier potassium channel 15 (KCNJ15); tyrosine-protein kinase Lyn (LYN); E3 ubiquitin-protein ligase Mdm2 (MDM2); and protein kinase C beta type (PRKCB). All the identified genes have a close relationship with neuronal and inflammatory mechanisms, the authors reported.
According to the study, the six-marker test had specificity of 85 percent and sensitivity of 91 percent in differentiating bipolar patients from those with depression. The authors stated in the paper that the test could eventually help to "reduce the misdiagnosis delay of bipolar patients, leading to an earlier implementation of a proper treatment."
Alcediag is now at work validating the next-generation sequencing and AI-based test together with a new European project called Edit-B. The project commenced earlier this year and has a total budget of €5.2 million ($5.5 million), €2.5 million of which is funded by the European Institute of Innovation and Technology for Health (EIT Health).
The Edit-B consortium includes Alcediag as well as the Center of Psychiatry of the Capital Region in Denmark; the Clinical Hospital of Barcelona, Spain; GHU Paris Psychiatry & Neurosciences; Hospital Parc Sanitari Sant Joan de Deu, also in Barcelona; Paris-based life sciences firm the ProductLife Group; and Synlab Italy. The four academic partners will serve as clinical trial centers for the project. By 2024, the consortium aims to recruit 436 patients with depression, half of whom will be diagnosed with bipolar disorder and the other with major depressive disorder.
According to the project's website, ProductLife will assist with quality management systems and regulatory issues around obtaining a CE-IVD mark for the test under the IVDR by 2025, which is a central aim of the project. Synlab Italy will assess the clinical performance of Edit-B, and its facility in Castenedolo will serve as the central lab for the analysis of all clinical samples. Synlab will also be a partner for marketing the test later.
Eduard Vieta, a professor of psychiatry at the University of Barcelona, is principal investigator on the Edit-B project. He said via email that he thinks the potential of Alcediag's test is "very high." Currently, Vieta said, bipolar disorder is diagnosed based on clinical interviews, which is subjective, both for the informant and the interviewer.
"Given that the treatment of bipolar depression is very different from the treatment of unipolar depression, the commonest form of depression, if this test proves to be useful, sensible, specific, and accurate, this would be a major step towards precision psychiatry," said Vieta.
What is now needed, maintained Vieta, is to validate the technology by enrolling patients with both types of depression to see if the results of the proof-of-concept study are reproducible in a separate and larger cohort.
"Our hope is that the test will work, and this would mean that the diagnosis of bipolar disorder will change forever," said Vieta. "Nevertheless, this needs to be proven using the most rigorous methodology, and this is what we are doing now."
There are a number of companies working on psychiatric disorders and targeting bipolar disorders, in particular. Albuquerque, New Mexico-based Circular Genomics was founded last year to commercialize a test for depression based on circular RNA biomarker technology licensed from the University of New Mexico. The company raised $4.5 million in seed funding in December. Another firm of interest is MindX Sciences, an Indianapolis-based venture, that offers molecular tests to help guide treatment selection for patients with psychiatric conditions.
Alcediag's Weissmann said that the company has interests beyond testing for bipolar disorder. Other indications of interest include depression, schizophrenia, and tests that can assess patient responses to treatment. She added that Alcediag is planning a financing round to support the launch of Edit-B and future test development but did not say how much the company would like to raise.