Asia-Pacific Biotech News

Unlocking New Possibilities: From Cholesterol Drug to Treatment for Corneal Nerve Damage

An interview with Dr Tan Hong Chang, Senior Consultant at the Singapore General Hospital, and Associate Professor Liu Yu-Chi, Clinician Scientist at the Singapore National Eye Centre, on diabetic corneal neuropathy and a potential new treatment developed from an existing drug.

According to the World Health Organization, there are an estimated 422 million people living with diabetes in the world. Diabetes is a chronic health condition that affects how your body breaks down sugar (i.e. glucose). People with diabetes are at higher risk of other health complications like heart attack, stroke, and kidney failure. Among these include a lesser-known but significant complicated called diabetic corneal neuropathy.

How does this condition come about, what are the current treatment options, and how does it work? We speak to Dr Tan Hong Chang, Senior Consultant from the Department of Endocrinology at the Singapore General Hospital, and Associate Professor Liu Yu-Chi, Clinician Scientist at the Singapore National Eye Centre, to find out more.


1. What is diabetic corneal neuropathy and how prevalent is this among diabetic patients?

The cornea is the most densely innervated tissue in the human body. Corneal nerves maintains the homeostasis and health of ocular surface by releasing a variety of neuromediators, mediating tear reflex, tear production and blinking. Metabolic changes when diabetes mellitus (DM) is not controlled cause degenerative changes and apoptosis of corneal nerves, resulting in diabetic corneal neuropathy (DCN). DCN affects 47-64% of DM patients in their clinical course.1 Clinical manifestations include corneal hypoesthesia (decreased corneal sensation), reduced blink rate, reduced tear secretion, tear film instability, ocular surface punctate keratopathy, corneal ulcer and even corneal perforation in severe cases.


2. What are the current treatment options available for patients with diabetic corneal neuropathy?

The current mainstay management for DCN and diabetic keratopathy focuses on symptomatic treatment such as ocular surface lubricants and prophylactic antibiotics. These treatments do not address the underlying pathophysiology, i.e., corneal neuropathy. Currently, topical recombinant NGF eye drops are the only Food and Drug Administration (FDA)-approved drug for treating patients with neurotrophic keratopathy. However, this treatment course is costly and requires frequent topical application. Moreover, it is not available locally. Hence, a novel, effective, and affordable treatment is crucially needed.


3. Fenofibrate is an existing drug that is used to lower cholesterol. Out of the many available drugs on the market, how did you and your team come to decide on working with fenofibrate?

It is known that dysregulated lipid metabolism takes part in the development and progression of diabetic neuropathy.2 Therefore, normalising lipid metabolism might ameliorate the risk of the development and progression of diabetic neuropathy. The fenofibrate intervention and event lowering in diabetes (FIELD) study have reported the neuroprotective effect of the fenofibrate as its systemic use reduced the overall neuropathy and improved the reversal of pre-existing neuropathy in type 2 DM.3 Hence, the team decided to investigate the potential protective effects of oral fenofibrate on DCN.


4. How does fenofibrate work to treat diabetic corneal neuropathy? What makes it better than the current available options?

We found that treatment with fenofibrate was associated with alterations in three pathways: (1) neuronal pathway, (2) lipid modulation, (3) anti-inflammation and anticoagulation. As the currently available option is extremely limited, and topical nerve growth factor eye drops are very costly, fenofibrate could be a new effective and affordable treatment option for DCN.


5. What’s next in this study? When can we expect to see fenofibrate rolled out for use to treat patients with this diabetic complication?

The next steps would be to conduct large-scale randomised controlled trials, among at least 200 patients, who will be selected largely from SNEC’s clinics. This will allow the team to fine-tune the dosage and treatment duration of patients with DCN, based on their disease severity. The next steps also include developing topical fenofibrate eye drops for better clinical adoption. The team is discussing with potential pharmaceutical companies to formulate fenofibrate into topical eye drops. The topical form will eliminate the systemic side effects of oral fenofibrate, improve patients’ compliance, and better clinical adoption.


6. Seeing the success of repositioning fenofibrate, how is drug repurposing altering the way we approach drug development? What are some challenges and opportunities?

Repurposing existing drugs is an attractive option for clinicians and researchers as it reduces the risk, cost, and timeline of the drug development process. Many potential repurposing drugs have been used in the clinical practice as off-label, non-registered uses. However, to register oral fenofibrate as an approved indication for diabetic corneal neuropathy, it still needs to go through the regulatory requirements, such as phase 3 trials and Chemistry, Manufacturing and Controls (CMC) dossier review by the Therapeutic Product, HSA, Singapore. [APBN]

About the Interviewees

 Dr Tan Hong Chang

Following the completion of his basic medical degree, Dr Tan Hong Chang underwent basic specialist training in internal medicine and subsequently subspecialty training in endocrinology at Singapore General Hospital. He is interested in clinical research, particularly in the study of metabolic fuel regulation abnormalities in various physiological and pathological states. He believes that the ability to manipulate how the body acquire, transport, integrate and utilise various nutrients is the key towards improving metabolic health.




Associate Professor Liu Yu-Chi

Associate Professor Liu Yu-Chi received her medical degree (MD) from Taipei Medical University, and gained her specialist and subspecialist accreditation in Ophthalmology and Cornea. She obtained her Master degree from the National University of Singapore (NUS) and PhD degree from Duke-NUS Medical School. Her clinical and research work is internationally recognized and has received 17 international or national awards, including the Achievement Award of Asia-Pacific Academy of Ophthalmology, and Clinician Scientist Award of National Medical Research Council. She is also named as one of the top 2% scientists worldwide.