- Email:
Repurposing of Existing Drugs for CNS Disorders
The incidence of CNS disorders such as Alzheimer's disease, Parkinson's disease, depression, anxiety and epilepsy continues to rise. These diseases place a heavy burden on the healthcare system. To alleviate this burden, the medical community is actively exploring new treatment strategies. One strategy that has gained momentum in recent years is the repurposing of existing drugs, which is a practical, fast and less risky alternative to traditional drug development methods.
Repurposing assigns new indications to previously approved drugs, taking advantage of known safety and pharmacokinetic profiles and accelerating the drug development process for CNS disorders. In this article, we delve into the complexities of repurposing existing drugs for CNS disorders, exploring the challenges, opportunities, and breakthroughs that are reshaping the therapeutic landscape.
Creative Biolabs is a leading biotechnology company providing comprehensive CNS drug discovery and development services, including drug repurposing solutions.
| Services | What We Do | Advantages |
|---|---|---|
| STEMOD™ Advanced Drug Discovery Service | We develop integrated technology platforms to provide one-stop CNS drug discovery services, including studies on BBB transport and distribution in the brain. |
|
| Custom CNS Disease Modeling Services | Our platform can provide reliable customized models, including but not limited to Alzheimer's disease models, Huntington's disease models, and Parkinson's disease models. |
|
| High Content Screening Service | HCS is used in all aspects of drug development, including primary compound screening, as well as early assessment of ADME (absorption, distribution, metabolism and excretion) and toxicity properties. Compared to high-throughput screening (HTS), HCS monitors multiple nodes in the cellular pathway with more predictable results. |
|
Mechanism of Repurposing Existing Drugs
The repositioning or repurposing of existing drugs is based on the principle that all drugs have multiple actions that may go beyond their original indications. This phenomenon, also known as polypharmacology, can be used to explore new therapeutic areas. Instead of starting the development process from scratch, scientists utilize the pharmacokinetic properties of existing drugs to treat different diseases. This approach results in significant savings in time and resources and minimizes potential safety risks.
Fig. 1 Chronology of drug repurposing approaches.1
In the face of the challenges of the complex pathophysiology of CNS disorders, the blood brain barrier (BBB) limiting drug access to the brain, and the lack of reliable preclinical models, repurposing existing drugs for the treatment of CNS disorders offers several distinct advantages.
- Reduced development time: by repurposing existing drugs, researchers can bypass many of the early stages of drug development, including lead compound identification, optimization, and preclinical safety testing. This accelerated timeline can significantly shorten the path to clinical translation.
- Lower development costs: Developing new drugs from scratch can cost more than billions of dollars and take up to a decade. In contrast, repurposing an existing drug may be more cost-effective because much of the preclinical and clinical safety data is already available, reducing the overall financial burden.
- Enhanced safety: Because repurposed drugs are often used in clinical practice for their original indications, they have a favorable safety profile, providing reassurance to regulators, clinicians, and others.
- Diversification of therapeutic options: Repurposing allows for the exploration of new therapeutic avenues for CNS disorders, with the potential to uncover unexpected benefits and improve patient outcomes.
Drug Repurposing Strategies for CNS Diseases
Drug repurposing for CNS disorders relies on a variety of strategies, each customized to address different aspects of drug pharmacology and disease biology. Some key approaches include:
| Strategies | Mechanisms |
|---|---|
| Target-based repurposing | This strategy involves identifying existing drugs that target specific molecular pathways involved in CNS diseases. By repurposing drugs with known mechanisms of action, researchers can utilize existing knowledge about target involvement and downstream effects to streamline the drug development process. |
| Phenotype-based repurposing | In phenotype-based repurposing, a drug is repurposed based on its observed effects in preclinical models or clinical settings through high-throughput phenotypic screen. |
| Network-based repurposing | The network pharmacology approach utilizes systems biology and network analysis to identify novel drug-disease associations based on the interconnectivity of biological pathways. By mapping the interactions between drugs, targets, and diseases, researchers can identify potential repurposing opportunities that may have been overlooked using traditional methods. |
| Drug combination strategies | Combining existing drugs with complementary mechanisms of action is another promising approach to repurposing CNS diseases. By synergistically targeting the multiple pathways involved in disease pathogenesis, combination therapies have the potential to improve efficacy and overcome treatment resistance. |
CNS Drug Repurposing Case Studies
Many FDA-approved drugs have been repurposed for the treatment of CNS disorders.
- For example, riluzole, which was originally developed for the treatment of amyotrophic lateral sclerosis (ALS), is currently in phase II trials for the treatment of spinal cord injury. The drug modulates glutamatergic transmission and acts as a neuroprotective agent, thereby inhibiting neuronal degradation.
- Similarly, lithium, which is primarily used to treat bipolar disorder, has been linked to neuroprotection and neurogenesis. Studies have shown that lithium alters the glycocortical system, sparing amyloid-beta proteins and reducing neuroinflammation in patients with Alzheimer's disease. Trials are currently underway to evaluate the potential role of lithium in the treatment of diseases such as Huntington's disease and acromegaly.
- In addition, sodium valproate has been studied for its neuroprotective effects in neurodegenerative diseases as an antiepileptic drug. It exerts neuroprotective effects by inhibiting histone deacetylase. Its potential use in schizophrenia, bipolar disorder and major depressive disorder has also been investigated.
- Originally developed as an anesthetic, ketamine has emerged as a novel and fast-acting antidepressant for the treatment of patients with refractory depression (TRD). Despite its well-defined dissociative effects, the antidepressant properties of ketamine are attributed to its ability to modulate glutamatergic neurotransmission, leading to rapid synaptogenesis and restoration of synaptic plasticity.
- Originally developed as an antiviral drug, amantadine has found application in the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease (PD). Although the exact mechanism of its anti-motor effects is still not fully understood, amantadine is thought to modulate glutamatergic and dopaminergic neurotransmission within the basal ganglia circuit.
Drug repurposing offers a cost-effective and time-saving approach to CNS drug development. Rapid technological advances coupled with a deeper understanding of disease mechanisms strongly support the promise of drug repurposing.
Future research should focus on building a robust, systematic and versatile drug repurposing pipeline using high-throughput and computational technologies. With the right strategies and policies, drug repurposing will dramatically change the therapeutic landscape of CNS diseases.
Reference
- Shukla, Rammohan, et al. "Signature-based approaches for informed drug repurposing: targeting CNS disorders." Neuropsychopharmacology 46.1 (2021): 116-130.
For Research Use Only. Not For Clinical Use.