Drug Repurposing For Neurodegenerative Diseases is a treatment approach for neurodegenerative diseases. This page provides comprehensive information about its mechanism of action, clinical evidence, and therapeutic potential.
Drug repurposing (also called drug repositioning) involves identifying new therapeutic uses for existing drugs that were developed for other conditions. This approach offers significant advantages: established safety profiles, known pharmacokinetics, reduced development time, and lower costs [1].
| Advantage | Description | Impact |
|---|---|---|
| Known Safety | Extensive clinical use data | Reduced Phase 1 risk |
| Known PK/PD | Established dosing | Faster development |
| Manufacturing | Existing production | Lower cost |
| Regulatory | Established pathways | Faster approval |
| Property | Value |
|---|---|
| Original Indication | Type 2 diabetes |
| Mechanism | AMPK activation, mTOR inhibition |
| Neuroprotective Effects | Autophagy, mitochondrial biogenesis |
Clinical Evidence:
| Property | Value |
|---|---|
| Original Indication | Type 2 diabetes |
| Mechanism | GLP-1 receptor activation |
| CNS Effects | Neuroprotection, reduced neuroinflammation |
Clinical Evidence:
| Property | Value |
|---|---|
| Original Indication | Hypercholesterolemia |
| Mechanism | HMG-CoA reductase inhibition |
| Neuroprotective Effects | Anti-inflammatory, membrane effects |
Clinical Evidence:
| Property | Value |
|---|---|
| Original Indication | Hypertension |
| Mechanism | Calcium channel blocker |
| Neuroprotective Effects | Calcium homeostasis |
Clinical Evidence:
| Drug | Original Target | Neurodegeneration Target |
|---|---|---|
| Nilotinib | BCR-ABL, c-KIT | Autophagy, α-syn clearance |
| Bosutinib | BCR-ABL | Autophagy enhancement |
| Dasatinib | BCR-ABL | Senolytic effects |
Clinical Evidence:
| Drug | Original Indication | Neurodegeneration |
|---|---|---|
| Sirolimus | Transplant rejection | Autophagy induction |
| Everolimus | Cancer, tuberous sclerosis | mTOR inhibition |
Clinical Evidence:
| Property | Value |
|---|---|
| Original Indication | Bacterial infections |
| Mechanism | Anti-inflammatory, microglial modulation |
Clinical Evidence:
| Drug | Original Indication | Status |
|---|---|---|
| Ibuprofen | Pain/inflammation | Mixed results |
| Naproxen | Pain/inflammation | Failed in AD prevention |
Clinical Evidence:
| Drug | Potential Use | Mechanism |
|---|---|---|
| Sertraline | AD, PD depression | Serotonin modulation |
| Fluoxetine | Neuroprotection | BDNF increase |
Clinical Evidence:
| Property | Value |
|---|---|
| Original Indication | Depression |
| Mechanism | Sleep regulation, anti-Aβ |
Clinical Evidence:
| Property | Value |
|---|---|
| Original Indication | Epilepsy |
| Mechanism | HDAC inhibition, mood stabilization |
Clinical Evidence:
| Property | Value |
|---|---|
| Original Indication | Epilepsy |
| Mechanism | Synaptic modulation |
Clinical Evidence:
| Drug | Original Use | Neurodegeneration Target |
|---|---|---|
| Amphotericin B | Antifungal | Prion disease |
| Atovaquone | Antiprotozoal | Mitochondrial function |
| Mebendazole | Anti-parasitic | Microtubule stabilization |
| Doxycycline | Antibiotic | Anti-inflammatory |
| Method | Description |
|---|---|
| Gene Expression | Connective Alchemy 基于表达谱 |
| Network Analysis | Protein-protein interaction networks |
| Signature Matching | Compare disease and drug signatures |
| Platform | Approach |
|---|---|
| Connectivity Map | Gene expression matching |
| Repurpose | Open-source drug database |
| DrugBank | Computational screening |
| Drug | Original Indication | New Indication | Phase | NCT |
|---|---|---|---|---|
| Liraglutide | Diabetes | Alzheimer's | 3 | NCT04777409 |
| Semaglutide | Diabetes | Alzheimer's | 3 | NCT05277311 |
| Dapagliflozin | Diabetes | Parkinson's | 2 | NCT04162986 |
| Atovaquone | Malaria | ALS | 2 | NCT03704589 |
| Nilotinib | CML | Parkinson's | 2 | NCT03782839 |
| Combination | Rationale | Status |
|---|---|---|
| Metformin + Lifestyle | Metabolic + behavioral | Preclinical |
| GLP-1 + Exercise | Synergistic effects | Planning |
| Senolytic combination | Enhanced clearance | Phase 1 |
The study of Drug Repurposing For Neurodegenerative Diseases has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[1] Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004;3(8):673-683.
[2] Campbell JM, et al. Metformin and Alzheimer's disease: a systematic review. J Diabetes Res. 2018;2018:2063247.
[3] Athauda D, et al. Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390(10103):1664-1675.
[4] Pagan F, et al. Nilotinib effects in Parkinson's disease and dementia with Lewy bodies. J Parkinsons Dis. 2022;12(1):193-207.