Dronedarone Shows Promise as a Repurposed Drug for Colitis Treatment, Says Prof. Liu Huanliang of The Sixth Affiliated Hospital of Sun Yat-sen University

In 1988, after receiving the Nobel Prize in Physiology or Medicine, James Black uttered the famous quote: “The best way to discover a new drug is to start with an old one.”

The literal translation into Chinese is "discovery."The Best Approach to Developing New Drugs Is to Start with Existing OnesSince then, the field of “drug repurposing” has seen a surge in discoveries. For instance, lidocaine, originally used for analgesia, was later found to have central antitussive effects; methotrexate, initially developed for cancer treatment, has also shown remarkable efficacy in managing immune-mediated diseases such as rheumatoid arthritis…

Professor Liu Huanliang’s Team at the Sixth Affiliated Hospital of Sun Yat-sen UniversityThe team has achieved remarkable success in the fields of in vitro diagnostics and drug development for gastrointestinal diseases, securing over 20 national invention patents and PCT patents. This time, they have also made innovative attempts at "drug repurposing."

Through screening and multiple trials, Professor Liu’s team discoveredAntiarrhythmic Drug DronedaroneIt demonstrates significant efficacy in the treatment of colitis. Furthermore, since dronedarone received FDA approval for market launch as early as 2009, it boasts a high level of market maturity. Consequently, upon successful completion of clinical trials, it can be rapidly introduced to the market, providing a new therapeutic option for a broader population of patients with colitis.

So, how did Professor Liu’s team screen out dronedarone from numerous drugs? What are the differences in the process of translating approved FDA drugs into practical applications?“Sci-Tech China” The 2nd High-Value Biomedical Patent Project SelectionAt the invitation of VCBeat, Professor Liu Huanliang engaged in an in-depth discussion with Artery Orange Fruit Bureau.

In the past, many instances of “drug repurposing” stemmed from serendipitous clinical observations by physicians. With advancements in technology and increasingly in-depth drug research, the practice of repurposing existing drugs has gradually moved away from relying on chance and become more targeted. Professor Liu Huanliang’s team investigated dronedarone for the treatment of colitis, representing a clearly purposeful endeavor.

Colitis, as the name implies, refers to a series of inflammatory pathological changes occurring in the colon. The inflammatory response is, in fact, a crucial active defense mechanism of the body. When the immune system detects pathogen invasion, the human body automatically activates certain intracellular signaling pathways, leading to the transcription of cytokines that mediate the immune response; these cytokines may induce inflammation.

The Inflammatory Response in Patients with Colitis andNF-κB Signaling Pathway...are closely associated with these abnormalities. In other words, identifying drugs that target the NF-κB signaling pathway can precisely pinpoint the inflammatory sites in colitis, thereby exerting a therapeutic effect.

Consequently, Professor Liu’s team screened nearly a thousand drugs from the FDA-approved drug library and identified a cohort of candidates potentially targeting the NF-κB signaling pathway using cellular models.

However, drug efficacy is not the sole criterion in drug screening; providing patients with effective and comfortable pharmacological treatments is equally important.

Therefore, Professor Liu’s team conducted a case-by-case investigation into the clinical applications and side effects of the shortlisted drugs, thereby identifying another batch of candidates.Minor side effectsof the drug. Subsequently, Professor Liu’s team applied the drug to animal models and identified agents capable of reducing the disease activity index and alleviating symptoms such as weight loss and diarrhea in mice.

After rigorous screening, two drugs ultimately emerged as frontrunners in this competition: one is for the treatment of postmenopausal osteoporosisBazedoxifene, another one is antiarrhythmicDronedarone. Professor Liu’s team simultaneously conducted research on two drugs, aiming to identify the one more suitable for treating inflammatory bowel disease.

However, in later studies, Professor Liu’s team discovered《Nature》A prior publication was the first to report the therapeutic effects of bazedoxifene in a zebrafish model of colitis. This caused his team to miss out on patent protection for the use of bazedoxifene in treating colitis. Consequently, Professor Liu led his team to focus on investigating the therapeutic effects of dronedarone in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the intestine, characterized by a protracted and refractory course. It causes recurrent abdominal pain, diarrhea, and bloody stools, severely impairing patients’ quality of life. In recent decades, with advancing industrialization, the incidence of IBD has increased several-fold. According to data from the Chinese Center for Disease Control and Prevention in 2014, the total number of IBD cases in China between 2005 and 2014 was approximately 350,000.It is estimated that by 2025, the number of IBD patients in China will reach 1.5 million.To a certain extent, it poses a threat to public health and safety.

To date, the etiology of inflammatory bowel disease (IBD) remains unclear, and there is no curative treatment. Pharmacological therapy remains the mainstay of IBD management; however, if the disease is poorly controlled and progressively worsens, patients may develop complications such as massive hemorrhage, enterocutaneous fistula, and intestinal obstruction, necessitating surgical intervention, which may need to be performed multiple times.

In recent years, the continuous launch of biologic agents has provided new treatment options for patients with inflammatory bowel disease (IBD). However, there is significant interindividual variability in the efficacy of these biologics. Even with anti-tumor necrosis factor (anti-TNF) monoclonal antibodies, which have the fastest onset of action and the most potent anti-inflammatory effects, less than 50% of patients achieve mucosal healing after treatment. Furthermore, these biologic agents are associated with risks such as allergic reactions, potential infections, and primary or secondary loss of response.

Therefore, it is imperative to identify a drug that is both effective and has minimal side effects.

Through research and multiple trials conducted by Professor Liu’s team, it has been found that dronedarone may be a medication capable of addressing this “urgent need.”

First, dronedarone was approved for marketing in China as early as 2012. Over the past decade, dronedarone has demonstrated a low incidence of adverse reactions and mild side effects, and it has even been recommended as a first-line agent for long-term rhythm control in patients with atrial fibrillation by multiple authoritative domestic and international guidelines. Therefore, the drug has a very high safety profile.

In addition, compared with traditional medications for the treatment of inflammatory bowel disease,Fewer side effects. For instance, long-term use of glucocorticoids and immunosuppressants may induce or exacerbate infections, leading to the dissemination of latent infectious foci or the reactivation of dormant infections, thereby causing secondary harm to patients' health.

However, dronedarone exerts its inhibitory effects via the NF-κB signaling pathway, a mechanism fundamentally distinct from that of conventional drugs, thereby naturally avoiding such severe adverse effects.

Secondly, dronedarone'sThe therapeutic efficacy is also excellent., in addition to significantly inhibiting the NF-κB signaling pathway in cellular models, it also demonstrated marked anti-inflammatory effects in a dextran sulfate sodium (DSS)-induced acute colitis model, effectively reducing the disease activity index and alleviating symptoms.

Finally, as dronedarone has been in existence for several decades, its manufacturing process is highly mature compared to that of biologic drugs,Lower cost price, which significantly alleviates the financial burden on patients.

Professor Liu told VCBeat’s Orange Fruit Bureau: “It is conceivable that dronedarone will achieve high patient acceptance, whether in terms of therapeutic efficacy, side effects, or even price. As a next step, we will”Dosage, efficacy, and across different dosage forms...design to enhance the efficacy of dronedarone in the treatment of colitis, enabling patients with colitis to access safe and effective medications at an earlier stage.”

As is well known, the new drug development cycle is very long, with an average of15 yearsBeyond the time invested, R&D costs also require hundreds of millions of dollars or even more. Furthermore, the vast majority of drug candidates fail to pass the Phase I safety evaluation and are terminated immediately, resulting in a success rate of less than 10%. Therefore, new drug development has always been a process that demands meticulous, time-intensive effort, where a single misstep can lead to total failure.

And "drug repurposing" canSkip the Phase I drug toxicity evaluation, directly validating drug efficacy, thereby achieving low cost and low risk while improving success rates. This is also the advantage of dronedarone’s translation.

In addition, the strength of Professor Liu’s team and the institutional platform have provided robust support for the translational development of dronedarone.

where his team is basedThe Sixth Affiliated Hospital of Sun Yat-sen University, it is home to a leading inflammatory bowel disease (IBD) center in China with international renown, serving a large population of IBD patients and maintaining a comprehensive case database. The team members possess extensive medical background and experience in clinical diagnosis and treatment, biomarker screening, and drug target development.

Only through the integration of industry, academia, and research can the commercialization of scientific and technological achievements be promoted. Professor Liu stated, “Currently, we are seeking collaboration with relevant enterprises to further refine this patented technology.“...and in the process, train more clinicians and research personnel. Under the guidance and platform support of The Sixth Affiliated Hospital of Sun Yat-sen University’s spirit of entrepreneurship, excellence, and innovation, we will maximize our team’s potential and contribute to the Healthy China 2030 initiative.”

Cultivating researchers involves equipping them with past knowledge, empowering them to create new possibilities. Similarly, “drug repurposing” also explores the future by drawing on the past.

From initial drug discovery to eventual clinical application, candidates must survive a perilous journey fraught with numerous hurdles, including multi-level assessments of bioactivity and efficacy, investigations into target specificity and mechanisms of action, and evaluations of toxicity and safety.

Drugs that have already withstood rigorous testing can rapidly meet the basic requirements for safety evaluation and metabolism, thereby accelerating the process of new drug discovery. Therefore, “drug repurposing” is bound to become a significant driving force in humanity’s protracted battle against disease.