Exploring the Potential of Existing Drugs for New Therapeutic Applications
Drug repurposing, also recognized as drug reprofiling, involves identifying new therapeutic applications for existing or investigational drugs, expanding their use beyond their original purpose. Unlike conventional drug discovery, which is a lengthy, risk-laden, and costly journey from concept to approved medicine, the repurposing strategy has emerged as a crucial tactic to accelerate the drug development process, providing swift solutions to unmet medical needs.
This alternative strategy optimizes the time and expense involved in pharmaceutical research by uncovering new applications for already approved or investigational drugs, without altering their chemical structure. Utilizing previously recognized biological properties for different therapeutic indications, successful repositioning efforts have surfaced for treating various pathologies over recent years.
By employing this approach, drug repositioning enhances the success rate of drug development. It trumps traditional methodologies by shortening development times, increasing efficiency, and mitigating risks and costs. Such a strategy proves especially valuable when the traditional de novo drug discovery is deemed cost-prohibitive, or an urgent cure is required.
When it comes to rare diseases, fewer treatment options are available. Developing new treatments for these conditions is challenging, often due to limited patient populations, insufficient understanding of disease pathology, high development costs, and disease complexity. Collaborative strategies amplify the effectiveness of drug development efforts by integrating resources, expertise, and data.
Drug repurposing typically involves partnerships among academic institutions, pharmaceutical companies, and patient advocacy groups. These collaborations pool knowledge and resources, yielding more efficient and potent drug development pathways.
Repurposing is often a serendipitous process, with discoveries made unexpectedly. Advances in fields like genomics, network biology, and chemoproteomics have empowered researchers to pinpoint potential repurposing candidates by identifying disease-associated genes and their interactions with known drug targets.
Approaches and Applications
Drug repurposing could commence through one of three approaches: drug-centric, disease-centric, or target-centric, each exploring the relationship between drugs, diseases, and targets differently based on therapeutic actions.
The drug-centric approach involves recognizing off-label uses for approved drugs in new patient populations or medical conditions outside their licensed scope. It involves evaluating abandoned drugs once dismissed for poor efficacy or regulatory rejection.
The disease-centric method investigates diseases with little to no treatment that could benefit from existing or failed compounds. It identifies those with biological mechanisms matching original drug indications.
The target-centric approach examines molecular targets implicated in disease paths, using existing drugs to modulate these targets, particularly for rare diseases.
Scientific Foundations
Two scientific pillars for drug repurposing arise from insights gained through human genome research, uncovering shared biological targets across diseases. With extensive data mining, ligand-based, and structure-based methods, alongside machine learning, drug repurposing capabilities can be improved.
Today’s technologies permit defining diseases using molecular profiles and applying computational methods to identify similar diseases sharing molecular traits.
Highlighting overlapping biological targets, conditions like Parkinson’s and Alzheimer’s share 48 genes and four signaling pathways. The presence of protein targets common to multiple diseases suggests that a single drug can potentially treat both. Drugs currently available in the market are phenotypically well-characterized by their therapeutic efficacies and side effects, underscoring these points.
Repurposing Challenges
A significant hurdle in drug repurposing is weak intellectual property protection, potentially diminishing returns on investment and discouraging further development by companies.
Once a new chemical entity is patented, subsequent medicines containing the same entity can only gain protection through narrower application patents.
Renowned examples like aspirin and sildenafil exemplify successful repurposing. Initially used for pain relief and as an anti-inflammatory, aspirin found a new role in preventing cardiovascular conditions. Sildenafil, developed as an antihypertensive drug, found new life treating erectile dysfunction, reflecting drug repurposing’s substantial impact.
The author is a Professor & Principal at the National College of Pharmacy, Manassery, Kozhikode