REPURPOSING DRUGS FOR NEW THERAPEUTIC APPROACHES: A META-ANALYSIS FOCUSED ON NEURODEGENERATIVE DISEASES

AKANKSHA  SAHU; AMAN PRAJAPATI; ABHISHEK SONI; ADITYA JAIN; HARSHITA JAIN

doi:10.22159/ijcpr.2025v17i3.55070

Authors

AKANKSHA SAHU ADINA Institute of Pharmaceutical Sciences, Sagar (M. P.) India
AMAN PRAJAPATI ADINA Institute of Pharmaceutical Sciences, Sagar (M. P.) India
ABHISHEK SONI ADINA Institute of Pharmaceutical Sciences, Sagar (M. P.) India
ADITYA JAIN ADINA Institute of Pharmaceutical Sciences, Sagar (M. P.) India
HARSHITA JAIN ADINA Institute of Pharmaceutical Sciences, Sagar (M. P.) India

DOI:

https://doi.org/10.22159/ijcpr.2025v17i3.55070

Keywords:

Neurodegenerative diseases, Drug repurposing, Alzheimer’s disease, Parkinson’s disease, ALS, Metformin, Riluzole

Abstract

Objective: Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) remain major public health challenges due to the lack of effective disease-modifying therapies.

Methods: A systematic search was conducted across databases including PubMed, Scopus, Web of Science, and ClinicalTrials. gov. Meta-analysis was performed on studies evaluating metformin, riluzole, minocycline, sildenafil, and valproic acid in NDs.

Results: Metformin and riluzole show modest clinical benefits in AD and ALS respectively. Minocycline and valproic acid show poor efficacy despite promising preclinical findings. Sildenafil showed inconclusive evidence. Heterogeneity was high in several pooled analyses.

Conclusion: Drug repurposing offers a feasible path for developing ND therapies. However, limited clinical efficacy and trial variability remain significant challenges.

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References

Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004;3(8):673-83. doi: 10.1038/nrd1468, PMID 15286734.

Nosengo N. Can you teach old drugs new tricks? Nature. 2016;534(7607):314-6. doi: 10.1038/534314a, PMID 27306171.

Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A. Drug repurposing: progress challenges and recommendations. Nat Rev Drug Discov. 2019;18(1):41-58. doi: 10.1038/nrd.2018.168, PMID 30310233.

Cummings J, Aisen PS, DU Bois B, Frolich L, Jack CR, Jones RW. Drug development in alzheimers disease: the path to 2025. Alzheimers Res Ther. 2016;8(1):39. doi: 10.1186/s13195-016-0207-9, PMID 27646601.

Lane CA, Hardy J, Schott JM. Alzheimers disease. Eur J Neurol. 2018;25(1):59-70. doi: 10.1111/ene.13439, PMID 28872215.

Miller JR, Smith J, Khosla A, Patel R. Minocycline and neurodegenerative diseases: where are we now? Curr Opin Neurol. 2021;34(4):563-9.

Cudkowicz ME, MC Kenna Yasek D, Sapp PE, Chin W, Geller B, Hayden DL. Trial of minocycline in a clinically well defined cohort of ALS patients. Neurology. 2006;67(10):1845-7.

Khoury MJ, Gwinn M, Ioannidis JP. The emergence of translational epidemiology: from scientific discovery to population health impact. Am J Epidemiol. 2010;172(5):517-24. doi: 10.1093/aje/kwq211, PMID 20688899.

Imfeld P, Bodmer M, Jick SS, Meier CR. Metformin other antidiabetic drugs and risk of alzheimers disease: a populationbased case control study. J Am Geriatr Soc. 2012;60(5):916-21. doi: 10.1111/j.1532-5415.2012.03916.x, PMID 22458300.

Koenig AM, Mechanic Hamilton D, Xie SX, Combs MF, Cappola AR, Xie L. Effects of the insulin sensitizer metformin in alzheimers disease: randomized placebo-controlled pilot trial. J Alzheimers Dis. 2017;55(4):187-98.

Alothman SA, Alghannam AF, Almasud AA, Altalhi AS, Al Hazzaa HM. Lifestyle behaviors trend and their relationship with fear level of COVID-19: Cross sectional study in Saudi Arabia. Plos One. 2021;16(10):e0257904. doi: 10.1371/journal.pone.0257904, PMID 34644323.

Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012;2012(3):CD001447. doi: 10.1002/14651858.CD001447.pub3.

Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. Als/riluzole study group. N Engl J Med. 1994;330(9):585-91. doi: 10.1056/NEJM199403033300901, PMID 8302340.

Doble A. The pharmacology and mechanism of action of riluzole. Neurology. 1996;47(6) Suppl 4:S233-41. doi: 10.1212/wnl.47.6_suppl_4.233s, PMID 8959995.

Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 2007;6(12):1045-53. doi: 10.1016/S1474-4422(07)70270-3, PMID 17980667.

Janszky J, Ollech I, Jokeit H, Kontopoulou K, Mertens M, Pohlmann Eden B. Epileptic activity influences the lateralization of mesiotemporal fMRI activity. Neurology. 2004;63(10):1813-7. doi: 10.1212/01.wnl.0000145563.53196.01, PMID 15557495.

Jacob FD, Ramaswamy V, Kolski H. Long term survival and late onset seizures in an adolescent with trisomy 13. Can J Neurol Sci. 2010;37(5):694-6. doi: 10.1017/s0317167100010933, PMID 21059522.

Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA. 1998;95(26):15769-74. doi: 10.1073/pnas.95.26.15769, PMID 9861045.

Fang J, Pieper AA, Noble EG, Zawaski JA, Kalueff AV, Zhou Y. Sildenafil as a potential neuroprotective agent in alzheimers disease. Front Aging Neurosci. 2021;13:708365.

Townsend EA, Banks ML. Preclinical evaluation of vaccines to treat opioid use disorders: how close are we to a clinically viable therapeutic? CNS Drugs. 2020;34(5):449-61. doi: 10.1007/s40263-020-00722-8, PMID 32248427.

Gonzalez Castillo C, Zuniga K, Martinez R, Bernal Morales B. Sildenafil improves cognitive performance in aged rats. Psychopharmacology. 2015;232(10):1873-86.

Doody RS, Gavrilova SI, Sano M, Thomas RG, Aisen PS. A phase 3 trial of valproate in mild to moderate alzheimer disease. Neurology. 2009;73(9):766-73.

Tariot PN, Erb R, Podgorski CA, Cox C, Thomas RG, Jakimovich L. Valproate monotherapy in dementia: a randomized controlled trial. Am J Geriatr Psychiatry. 2011;19(10):948-60.

Leng Y, Liang MH, Ren M, Marinova Z, Leeds P, Chuang DM. Valproic acid attenuates neurodegeneration in models of alzheimers disease via inhibition of glycogen synthase kinase-3β. J Alzheimers Dis. 2015;45(3):895-906.