Crohn’s Disease is on the rise: Could drug repurposing help?

By Jinhan Kim, Co-founder and CEO, Standigm
Twitter: @standigm

The number of patients with Crohn’s Disease (CD) is set to rise from 1.4 million to 1.55 million or 7% in 2029 across France, Germany, Spain, UK and the U.S. The prevalence of CD is the highest in the U.S. at 243 cases per 100,000 persons. CD is an idiopathic chronic, transmural inflammatory process of the bowel that can affect any part of the gastrointestinal tract from the mouth to the anus.

While the cause of CD remains unknown, many factors have increased the incidence of CD alone or in tandem with ulcerative colitis (UC) as part of Inflammatory Bowel Disease (IBD) that are the direct result of industrialization, urbanization, a Western lifestyle and other environmental factors.

Consuming red meats, fried foods, sugary beverages and refined carbohydrates are all associated with a higher risk of developing CD. Although no single environmental factor causes CD, research suggests that other environmental factors contribute to disease risk including genetic susceptibility, microbial factors, intestinal immune system defects and smoking. In fact, tobacco smokers are more likely than non-smokers to have a disease relapse after surgery.

A Western diet may change the gut flora, increasing the prevalence of CD because they impair gut resistance to bacteria, toxins and additives found in processed food. In addition, severe food poisoning can cause CD later in life. One study found that demonstrated anxiety induced micro-RNAs can decrease the inflammatory response, and may be a possible link between stress and the development of CD.

Canada and the U.S. are the highest-ranking countries for fast food consumption. These countries also have a significant presence of chemical pollution and a relatively high smoking population.

The limitations of current therapies

CD therapies are designed to suppress patients’ malfunctioning inflammatory immune system responses. The main drawback of TNF-alpha inhibitors is that not all CD patients respond to them. Only one-third of patients are in remission with the medications while another one-third are unresponsive. In the long term, approximately half of patients cease using anti-TNFs because they have proven ineffective. In late-stage clinical trials, numerous medications that target various immunological and inflammatory mediators have been found to be ineffective.

There is also a small, but significant probability of having a serious opportunistic infection while using anti-TNF therapy. A patient’s immunity may be lowered by predisposing conditions such as an underlying illness or medical treatment, allowing the organism to spread an infectious disease. There is also an increased risk of opportunistic infection related to immunomodulatory therapy (e.g., corticosteroids, methotrexate, azathioprine) and biological therapy (e.g., anti-TNF drugs and other monoclonal antibodies), especially when administered combined.

Anti-TNF therapy is also linked to an increased risk of bacterial infections. Histoplasmosis and blastomycosis reports have increased with the use of anti-TNF therapy. Anti-TNF therapy has also been linked to both primary and reactivated fungal infections. Inhibition of TNF-α can theoretically increase the risk of viral infections but has only recently become an increased area of research. Anti-TNF therapy should always be withheld until an active pneumococcal infection is treated. Anti-TNF therapy may impair the response to pneumococcal vaccination, so the vaccine is usually recommended at least two or three weeks prior to starting anti-TNF therapy.

Drug repurposing provides a faster track to treatment

Drug repurposing provides a more efficient means of discovering a new treatment for a disease or disorder than discovering a novel drug. Unlike a novel therapy, a repurposed drug may be approved or not proven to be sufficiently effective in clinical trials. Either way, repurposed drugs have proven to offer some level of stability and the use of an existing drug reduces the development period. Pharmaceutical companies benefit monetarily from the drug’s repurposing because the drug is applied to a wider range of diseases or disorders. It is also more cost-effective for patients and insurance companies than a novel drug.

For example, we engaged in collaborative research with SK Chemicals in which we identified and validated repurposed drug candidates for Rheumatoid Arthritis. Since these candidates are likely to have anti-inflammatory and antirheumatic properties, they were expected to be effective therapies for CD. After conducting basic validations, we filed a patent and are now in discussions with SK Chemicals regarding further CD studies.

We’ve found that AI is a necessary tool for both drug discovery and repurposing given the sheer amount of complexity involved in such research, including the vast numbers of possible diseases, disorders, treatments, side effects, contraindications, and more. The AI platform contains a predictive algorithm that learns hidden patterns between transcriptomic profiles and drug indications and predicts unknown novel indications of existing drugs based on their perturbed gene expression profiles. The two other models include a drug-target binding prediction model and a biological knowledge graph based on a therapeutic prediction model.

We’ve used the same tools for other research projects, including AI-driven drug candidates which target Mitochondrial diseases, Parkinson’s Disease, NASH, and cancer, respectively. With the help of AI, it’s possible to expedite the discovery of novel and repurposed treatments, bringing new rays of hope to doctors and patients alike.