NEW YORK – A team of researchers from the Royal College of Surgeons in Ireland University of Medicine and Health Sciences are working with Irish diagnostic company Serosep to develop a gene expression-based assay to determine which ulcerative colitis patients will likely progress to more severe forms of the disease.
The new partnership stems from a previous project wherein the researchers searched for specific DNA or RNA biomarkers "to identify ways and means of predicting which patient is going to progress in the disease course at an early stage," said Sudipto Das, a lecturer and principal investigator at RCSI School of Pharmacy and Biomolecular Sciences. In that research, the team found a set of genes that were highly expressed in ulcerative colitis patients who tend to progress in the disease course. Disease progression is defined by the researchers as not responding to the first line of treatment, which is usually 5-aminosalicylates medication, Das explained.
By defining which genes can be utilized to predict patient response to treatment, the first and second lines of treatments can be circumvented, and the patient can be saved from unnecessary treatments, he added.
Currently, the standard of care for ulcerative colitis diagnosis is an endoscopy that determines the presence of the disease based on levels of inflammation, Das said. While there are certain biochemical biomarkers that can be used for disease diagnosis, such as C-reactive protein, and histological markers, he said that the unmet need is being able to predict disease progression in the early stages.
After its first round of research, the team had conversations with Irish diagnostic company Serosep about their findings. The Limerick-based company was interested because it works mainly on diagnostics for gastrointestinal infectious diseases, but hadn't yet explored the ulcerative colitis space, Das said.
"There was an alignment in terms of what we are doing and what their interests are as a diagnostic company," he added.
David Clancy, Serosep's chief technology officer, echoed Das, saying there is "good synergy" between Serosep and RCSI. The company has focused largely on developing molecular diagnostics for infectious diseases and has a suite of gastrointestinal assays, he said, and a test for ulcerative colitis progression would allow it to reach new markets, including the companion diagnostic market, since the test can be used to determine treatment options.
"We would like to diversify … in an area where we have synergy and where we have capacity and expertise," Clancy said. It "ticks a lot of the boxes in terms of synergy and what we do now and the skill sets that we have."
Serosep offers a variety of tests, including the EntericBio test for detecting GI pathogens in stool and the RespiBio assay for detection of SARS-CoV-2, influenza A/B, and respiratory syncytial virus. The firm knows how to move tests from the research setting "to being an actual physical product that you can sell in a regulatory market," Clancy said, and is prepared to shepherd the eventual diagnostic test through the manufacturing, commercialization, and regulatory processes, "bridging the gap between the research and the market."
"We have a proven track record over a long period of time of developing and bringing products to that market, producing them for that market, and maintaining and supporting them in that market," he said.
Funding for the project, about €500,000 ($540,000), comes from both Serosep and the Enterprise Ireland Innovation Partnership Programme, Das said.
The RCSI team's research began with a discovery cohort of about 50 to 60 adult patients who had either progressed or not progressed in the disease course. The researchers identified about 32 genes that are overexpressed in patients that are progressing in treatment escalation and conducted further analysis, which has thus far flagged two genes that are highly sensitive for predicting disease progression, Das said. He declined to name the genes because the team is filing a patent application for them, although he noted they both have sensitivity and specificity over 85 percent for predicting disease progression. Das said the final patent and publication of data will likely come in the next year once the genes are validated in a larger cohort.
If the team is able to successfully validate any of the genes, they will work with Serosep to develop a gene expression assay and license the patent to the company and then move to a multicenter clinical trial, Das said.
Clancy noted that the regulatory and commercial pathways for the test haven't been decided, since it depends on the final output of the test but added that it will consider US Food and Drug Administration approval, IVDR certification, or UK Conformity Assessed marking. Serosep will be working with the researchers on assay design to make sure it is ready for further development and commercialization, he said.
The researchers specifically identified biomarkers in tissue, Das noted, but are looking to expand their work into blood to see if the same biomarkers are expressed in a noninvasive sample type. The side-by-side comparison of tissue and blood is "very much embedded" in this study because it will give more confidence in the validation of the genes, he noted.
The team is currently recruiting patients for its validation cohort and has collected more than 100 samples from multiple hospitals in Dublin. Das said the researchers are hoping to get at least 200 patients to further build out the cohort.
While ulcerative colitis is the main focus of this partnership, Das noted that some of the genes they've analyzed are implicated in other types of gastrointestinal disorders, including colorectal cancer, and that the team is interested in delving deeper into discovering how the genes are expressed in other diseases.
In addition, they are hoping to determine if any of the genes they analyzed could be therapeutic targets. "If we are able to develop … a small molecule inhibitor, or even develop some sort of an mRNA-based targeting system that allows downregulating these genes, that could then potentially become a treatment option to impede the disease progression," he said.
Although that research area doesn't fall under the Serosep partnership, the researchers have begun research on the therapeutic potential of the genes in parallel with the diagnostic uses, Das said.