Old Drugs, New Hope: Review Explores Repurposing Medicines for Rare Diseases

UK: Rare or uncommon diseases affect 1 in 5000 newborn babies globally, irrespective of geographic, ethnic, or socio-cultural background. Some rare diseases are more common in male babies. In most cases, a precise diagnosis may not be possible, and thus extremely difficult to treat and manage. Inevitably, collectively rare diseases pose a huge burden on healthcare with unimaginable socio-economic consequences.

In the ongoing battle against rare or ‘orphan’ diseases, drug repurposing—also known as drug repositioning—is emerging as a promising and cost-effective strategy. A recent review published in Apollo Medicine by Professor Dhavendra Kumar, Honorary Clinical Professor at Queen Mary University of London and Senior Consultant Adviser to Apollo Genomics Institutes, sheds light on the immense potential and current barriers associated with this evolving approach.

Prof. Kumar notes that Rare diseases, which often present as complex, multisystemic, and genetically rooted conditions, affect millions worldwide, with a disproportionate burden in low- and middle-income countries (LMICs). However, due to the small patient populations and high costs of new drug development, treatment options remain severely limited.

In conversation with Medical Dialogues, Dr. Kumar emphasized the critical need for economical yet effective solutions. “There is an enormous economic burden on families and healthcare systems dealing with rare diseases. Drug repurposing offers a glimmer of hope, especially for children and families struggling with lifelong conditions. It presents a safer and economically rational alternative to prohibitively expensive novel therapies,” he said.

The review highlights how repurposing existing, licensed drugs—already proven safe for other conditions—can fast-track treatment accessibility for rare disorders. By identifying shared molecular or genetic pathways between different diseases, researchers can apply known drugs to new indications, often with encouraging results.

Dr. Kumar cited several compelling examples. One such case is alkaptonuria, a rare metabolic disorder. A herbicide known as nitisinone, originally used to treat tyrosinemia type 1, showed positive results in alkaptonuria due to their shared metabolic pathway. Similarly, rapamycin, once discarded due to toxicity concerns, demonstrated remarkable tumour-suppressing effects in tuberous sclerosis complex (TSC) through its action on the mTOR signalling pathway.

Another notable success is the use of angiotensin receptor blockers (ARBs) like losartan and irbesartan—typically prescribed for hypertension—in managing rare vascular genetic conditions such as Marfan syndrome and Loeys-Dietz syndrome, due to their action on the TGF-beta signalling pathway. This drug is shown to slow down arterial or aortic wall weakness that could lead to rupture of splitting with life-threatening implications.

Prof. Kumar also mentioned metformin, widely used for type 2 diabetes, which has found utility in treating conditions like polycystic ovary syndrome (PCOS) and rare severe insulin resistance syndromes, underscoring the diverse scope of drug repositioning.

However, the path to clinical implementation is far from straightforward. “Before a repurposed drug can be safely prescribed for a new indication, we need robust molecular evidence and pilot clinical trials,” noted Dr. Kumar. He emphasized the need for strong regulatory oversight and international collaboration. Indian authorities, such as ICMR and CSIR, must actively support fair, well-governed clinical trials. If international regulatory bodies like the FDA or MHRA have approved such uses, Indian agencies could fast-track local approvals,” he added.

Technological innovations are expected to accelerate progress in this field. Machine learning and artificial intelligence (AI) are being harnessed to identify novel molecular targets and predict drug efficacy. Dr. Kumar highlighted the KUALA framework, which uses AI to identify multiple targets for kinase inhibitors—an approach that holds great promise for cancer drug repurposing.

“Drug repurposing is not only cost-efficient but also scientifically sound. With the right collaborations, investment in applied research, and regulatory flexibility, we can bring effective treatments for rare diseases within reach, especially in countries like India,” concluded Dr. Kumar.

As rare diseases continue to pose a global public health challenge, strategic drug repurposing stands as a beacon of hope, offering practical solutions to bridge gaps in treatment access and affordability.

Reference:

Kumar, D. Drug Repurposing for Rare (Orphan) Diseases—Scope and Limitations. Apollo Medicine. https://doi.org/10.1177/09760016241287308