Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson’s Disease
Gabriella Tandra, Amy Yoone, Rhea Mathew, Minzhi Wang, Chadwick M. Hales, Cassie S. Mitchell · 2023 · 17 citationsRead the paper
Parkinson's disease (PD) is a movement disorder caused by a dopamine deficit in the brain. Current therapies primarily focus on dopamine modulators or replacements, such as levodopa. Although dopamine replacement can help alleviate PD symptoms, therapies targeting the underlying neurodegenerative process are limited. The study objective was to use artificial intelligence to rank the most promising repurposed drug candidates for PD. Natural language processing (NLP) techniques were used to extract text relationships from 33+ million biomedical journal articles from PubMed and map relationships between genes, proteins, drugs, diseases, etc., into a knowledge graph. Cross-domain text mining, hub network analysis, and unsupervised learning rank aggregation were performed in SemNet 2.0 to predict the most relevant drug candidates to levodopa and PD using relevance-based HeteSim scores. The top predicted adjuvant PD therapies included ebastine, an antihistamine for perennial allergic rhinitis; levocetirizine, another antihistamine; vancomycin, a powerful antibiotic; captopril, an angiotensin-converting enzyme (ACE) inhibitor; and neramexane, an N-methyl-D-aspartate (NMDA) receptor agonist. Cross-domain text mining predicted that antihistamines exhibit the capacity to synergistically alleviate Parkinsonian symptoms when used with dopamine modulators like levodopa or levodopa-carbidopa. The relationship patterns among the identified adjuvant candidates suggest that the likely therapeutic mechanism(s) of action of antihistamines for combatting the multi-factorial PD pathology include counteracting oxidative stress, amending the balance of neurotransmitters, and decreasing the proliferation of inflammatory mediators. Finally, cross-domain text mining interestingly predicted a strong relationship between PD and liver disease.
What the full text shows
Theory or simulation- Antihistamines (specifically ebastine and levocetirizine) are predicted as promising repurposed adjuvant therapies for Parkinson's Disease (PD). (Based on cross-domain text mining of 33+ million PubMed articles)
- Ebastine and levocetirizine significantly improved PD-like side effects and lowered mRNA expression of PD markers when combined with levodopa. (Mouse models)
- Ebastine and levocetirizine dose-dependently decreased levels of inflammatory molecules (histamine and TNF-α). (Haloperidol-induced PD animal models)
- Ebastine and levocetirizine increase levels of dopamine, serotonin, and noradrenaline while decreasing acetylcholine levels. (Mouse models)
- Ebastine and levocetirizine increase activity of antioxidant enzymes (SOD, CAT, GSH) and decrease biomarkers of oxidative stress (MDA, nitrite). (Not specified)
- Other promising repurposed drug candidates identified include vancomycin, captopril, and neramexane. (Based on SemNet 2.0 hub analysis)
- Setup
- Knowledge graph derived from 33+ million biomedical journal articles from PubMed.
- How
- The study used SemNet 2.0 for natural language processing (NLP) and cross-domain text mining of 33+ million PubMed articles to create a knowledge graph. It employed hub network analysis and unsupervised learning rank aggregation (HeteSim scores) to identify and rank drug candidates related to levodopa and PD.
- Limitations
- Ebastine is not FDA-approved in the USA; neramexane production is discontinued; vancomycin carries antibiotic resistance risks. · Second-generation antihistamines have limited ability to cross the blood-brain barrier. · Potential overlap of side effects between antihistamines and levodopa-carbidopa. · Reliance on existing PubMed literature may overlook infrequent, differently worded, or newer/less-cited research; lack of data source quality weighting.
Summarized by Gemma 4 from the open-access full text · 8 Oct 2026. Read it