Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial
Open accessAbstract
Importance: This study evaluated nilotinib safety and its effects on biomarkers as a potential disease-modifying drug in Parkinson disease. Objectives: To assess nilotinib effects on safety and pharmacokinetics and measure the change in exploratory biomarkers in patients with moderately severe Parkinson disease. Design, Setting, and Participants: This was a single-center, phase 2, randomized, double-blind, placebo-controlled trial with 300 patients approached in clinic; of these, 200 declined to participate, 100 were screened, 25 were excluded, and 75 were randomized 1:1:1 into placebo; nilotinib, 150-mg; or nilotinib, 300-mg groups. Recruitment started on May 17, 2017, and ended April 28, 2018, and follow-up ended August 10, 2019. Parkinson disease was confirmed according to the UK Brain Bank diagnostic criteria and symptoms were stabilized with use of optimal levodopa and/or dopamine agonists and other medications used in Parkinson disease. Interventions: Nilotinib vs placebo, administered orally once daily for 12 months followed by a 3-month washout period. Main Outcomes and Measures: It was hypothesized that nilotinib is safe and can be detected in the cerebrospinal fluid, where it alters exploratory biomarkers via inhibition of Abelson tyrosine kinase and potentially improves clinical outcomes. Results: Of the 75 patients included in the study, 55 were men (73.3%); mean (SD) age was 68.4 (8.2) years. Doses of 150 or 300 mg of nilotinib were reasonably safe, although more serious adverse events were detected in the nilotinib (150 mg: 6 [24%]; 300 mg: 12 [48%]) vs placebo (4 [16%]) groups. The 150-mg nilotinib group showed an increase in cerebrospinal fluid levels of the dopamine metabolites homovanillic acid (159.80nM; 90% CI, 7.04-312.60nM; P = .04) and 3,4-dihydroxyphenylacetic acid (4.87nM; 90% CI, 1.51-8.23nM; P = .01), and the 300-mg nilotinib group showed an increase in 3,4-dihydroxyphenylacetic acid (7.52nM; 90% CI, 2.35-12.69nM; P = .01). The nilotinib 150-mg but not the nilotinib 300-mg group demonstrated a reduction of α-synuclein oligomers (-0.04 pg/mL; 90% CI, -0.08 to 0.01 pg/mL; P = .03). A significant reduction of hyperphosphorylated tau levels was seen in the nilotinib 150-mg (-10.04 pg/mL; 90% CI, -17.41 to -2.67 pg/mL; P = .01) and nilotinib 300-mg (-12.05 pg/mL; 90% CI, -19.21 to -4.90 pg/mL; P = .01) groups. Conclusions and Relevance: In this study, nilotinib appeared to be reasonably safe and detectable in the cerebrospinal fluid. Exploratory biomarkers were altered in response to nilotinib. Taken together, these data will guide the development of a phase 3 study to investigate the effects of nilotinib therapy in patients with Parkinson disease. Trial Registration: ClinicalTrials.gov identifier: NCT02954978.
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Clinical trials showed that Nilotinib can reduce disease-related biomarkers in both AD and PD patients.
“clinical trials showed that Nilotinib can reduce disease-related biomarkers in both AD and PD patients”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Pagan et al., 2019
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Cook, R. J., Dickens, B. M., & Fathalla, M. F. (2003) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780199241323.003.0025 · Cited by 10,813 · see citing works
Spillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382 · see citing works
Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., & Goedert, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6469 · Cited by 3,151 · see citing works
Alpha-synuclein and neurodegenerative diseases
Goedert, M. (2001) · Nature reviews. Neuroscience · doi:10.1038/35081564 · Cited by 1,402 · see citing works
Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine
Eisenhofer, G., Kopin, I. J., & Goldstein, D. S. (2004) · Pharmacological Reviews · doi:10.1124/pr.56.3.1 · Cited by 1,072 · see citing works
El‐Agnaf, O. M. A., Salem, S. A., Paleologou, K. E., Curran, M. D., Gibson, M. J., Court, J. A., Schlossmacher, M. G., & Allsop, D. (2006) · The FASEB Journal · doi:10.1096/fj.03-1449com · Cited by 715 · see citing works
Catecholamine metabolism: basic aspects and clinical significance.
Kopin, I. J. (1985) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06859-0 · Cited by 582 · see citing works
Does levodopa slow or hasten the rate of progression of Parkinson’s disease?
Fahn, S., & and the Parkinson Study Group (2005) · Journal of Neurology · doi:10.1007/s00415-005-4008-5 · Cited by 348 · see citing works
Hebron, M. L., Lonskaya, I., & Moussa, C. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt192 · Cited by 332 · see citing works
Nilotinib Effects in Parkinson’s disease and Dementia with Lewy bodies
Pagan, F., Hebron, M., Valadez, E. H., Torres-Yaghi, Y., Huang, X., Mills, R. R., Wilmarth, B. M., Howard, H., Dunn, C., Carlson, A., et al. (2016) · Journal of Parkinson’s Disease · doi:10.3233/jpd-160867 · Cited by 265 · see citing works
Karuppagounder, S. S., Brahmachari, S., Lee, Y., Dawson, V. L., Dawson, T. M., & Ko, H. S. (2014) · Scientific Reports · doi:10.1038/srep04874 · Cited by 264 · see citing works
Unequal group sizes in randomised trials: guarding against guessing
Schulz, K. F., & Grimes, D. A. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08029-7 · Cited by 250 · see citing works
Mahul‐Mellier, A., Fauvet, B., Gysbers, A. M., Dikiy, I., Oueslati, A., Georgeon, S., Lamontanara, A. J., Bisquertt, A., Eliezer, D., Masliah, E., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt674 · Cited by 220 · see citing works
Evidence that Resistance to Nilotinib May Be Due to BCR-ABL, Pgp, or Src Kinase Overexpression
Mahon, F., Hayette, S., Lagarde, V., Belloc, F., Turcq, B., Nicolini, F. E., Bélanger, C., Manley, P. W., Leroy, C., Étienne, G., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1008 · Cited by 212 · see citing works
Park, M., Cheon, S., Bae, H.-R., Kim, S.-H., & Kim, J. W. (2011) · Journal of Clinical Neurology · doi:10.3988/jcn.2011.7.4.215 · Cited by 195 · see citing works
DeRemer, D. L., Ustun, C., & Natarajan, K. (2008) · Clinical Therapeutics · doi:10.1016/j.clinthera.2008.11.014 · Cited by 172 · see citing works
Journal of Clinical & Cellular Immunology
Abcouwer, S. F. (2019) · Journal of Clinical & Cellular Immunology · doi:10.4172/2155-9899 · Cited by 162 · see citing works
Lonskaya, I., Hebron, M. L., Desforges, N. M., Schachter, J. B., & Moussa, C. E.-H. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1112-3 · Cited by 152 · see citing works
Lonskaya, I., Hebron, M. L., Desforges, N. M., Franjie, A., & Moussa, C. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201302771 · Cited by 139 · see citing works
Hebron, M. L., Lonskaya, I., Sharpe, K., Weerasinghe, P. P. K., Algarzae, N. K., Shekoyan, A. R., & Moussa, C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.419945 · Cited by 138 · see citing works
Pagán, F., Hebron, M. L., Wilmarth, B., Torres-Yaghi, Y. A., Lawler, A., Mundel, E. E., Yusuf, N., Starr, N. J., Arellano, J., Howard, H. H., et al. (2019) · Pharmacology Research & Perspectives · doi:10.1002/prp2.470 · Cited by 117 · see citing works
Mollenhauer, B., El‐Agnaf, O. M. A., Marcus, K., Trenkwalder, C., & Schlossmacher, M. G. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.10.90 · Cited by 114 · see citing works
Lonskaya, I., Hebron, M. L., Selby, S., Turner, R. S., & Moussa, C. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.07.070 · Cited by 93 · see citing works
Fowler, A. J., Hebron, M. L., Missner, A. A., Wang, R., Gao, X., Kurd-Misto, B. T., Liu, X., & Moussa, C. (2019) · Drugs in R&D · doi:10.1007/s40268-019-0266-z · Cited by 68 · see citing works
Hebron, M., Lonskaya, I., Olopade, P., Selby, S., Pagán, F., & Moussa, C. (2014) · Journal of Clinical & Cellular Immunology · doi:10.4172/2155-9899.1000259 · Cited by 67 · see citing works
Tau clearance improves astrocytic function and brain glutamate-glutamine cycle
Hebron, M. L., Javidnia, M., & Moussa, C. (2018) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2018.06.005 · Cited by 49 · see citing works
Heyburn, L., Hebron, M. L., Smith, J. A. I., Winston, C. N., Bechara, J., Li, Z., Lonskaya, I., Burns, M. P., Harris, B. T., & Moussa, C. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13763 · Cited by 41 · see citing works
BCR-ABL1 Kinase: Hunting an Elusive Target with New Weapons
Skórski, T. (2011) · Chemistry & Biology · doi:10.1016/j.chembiol.2011.11.001 · Cited by 18 · see citing works
Flagged first, then by citations
3 of the 32 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Bloem, B. R., Okun, M. S., & Klein, C. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00218-x · Cited by 3,920 · see citing works
Inflammation and immune dysfunction in Parkinson disease
Tansey, M. G., Wallings, R. L., Houser, M. C., Herrick, M. K., Keating, C. E., & Joers, V. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-022-00684-6 · Cited by 1,382 · see citing works
Basheer, N., Smolek, T., Hassan, I., Liu, F., Iqbal, K., Zilka, N., & Novak, P. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02113-z · Cited by 159 · see citing works
Simuni, T., Fiske, B., Merchant, K., Coffey, C. S., Klingner, E., Caspell-Garcia, C., Lafontant, D.-E., Matthews, H., Wyse, R. K., Brundin, P., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2020.4725 · Cited by 149 · see citing works
Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer’s Disease
Turner, R. S., Hebron, M. L., Lawler, A., Mundel, E. E., Yusuf, N., Starr, J. N., Anjum, M., Pagan, F., Torres‐Yaghi, Y., Shi, W., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25775 · Cited by 126 · see citing works
Self-citationNovel targeted therapies for Parkinson’s disease
Ntetsika, T., Papathoma, P.-E., & Markaki, I. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00279-2 · Cited by 112 · see citing works
Recent Advances in Drug Therapy for Parkinson's Disease
Murakami, H., Shiraishi, T., Umehara, T., Omoto, S., & Iguchi, Y. (2022) · Internal Medicine · doi:10.2169/internalmedicine.8940-21 · Cited by 114 · see citing works
The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer
Elkamhawy, A., Lu, Q., Nada, H., Woo, J., Quan, G., & Lee, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126535 · Cited by 105 · see citing works
α-Synuclein pathology as a target in neurodegenerative diseases
Park, H.-J., Kam, T., Dawson, V. L., & Dawson, T. M. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-01043-w · Cited by 113 · see citing works
La Barbera, L., Vedele, F., Nobili, A., Krashia, P., Spoleti, E., Latagliata, E. C., Cutuli, D., Cauzzi, E., Marino, R., Viscomi, M. T., et al. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102031 · Cited by 98 · see citing works
Wise, R. M., Wagener, A., Fietzek, U. M., Klopstock, T., Mosharov, E. V., Zucca, F. A., Sulzer, D. L., Zecca, L., & Burbulla, L. F. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105920 · Cited by 95 · see citing works
Treatment of Parkinson’s Disease with Cognitive Impairment: Current Approaches and Future Directions
Sun, C. E., & Armstrong, M. J. (2021) · Behavioral Sciences · doi:10.3390/bs11040054 · Cited by 95 · see citing works
Expanding the role of proteasome homeostasis in Parkinson’s disease: beyond protein breakdown
Bi, M., Du, X., Jiao, Q., Chen, X., & Jiang, H. F. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03441-0 · Cited by 87 · see citing works
Role of Ubiquitin–Proteasome and Autophagy-Lysosome Pathways in α-Synuclein Aggregate Clearance
Sahoo, S., Padhy, A. A., Kumari, V., & Mishra, P. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02897-1 · Cited by 82 · see citing works
Payne, T., Appleby, M., Buckley, E., van Gelder, L. M. A., Mullish, B. H., Sassani, M., Dunning, M. J., Hernandez, D., Scholz, S. W., McNeill, A., et al. (2023) · Movement Disorders · doi:10.1002/mds.29450 · Cited by 76 · see citing works
Kim, J.-E., Lee, H., Park, J., Cha, B., & Hoe, H. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02549-0 · Cited by 72 · see citing works
Angelopoulou, E., Paudel, Y. N., Shaikh, M. F., & Piperi, C. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104930 · Cited by 64 · see citing works
Yang, J., Zhi, W., & Wang, L. (2024) · Molecules · doi:10.3390/molecules29122812 · Cited by 63 · see citing works
“Nilotinib, a small-molecule inhibitor of Bcr-Abl, had some effect on CSF and frontal cortex amyloid levels in a phase 2 clinical trial but failed to exert an effect on tau [181–183].”
BackgroundLong‐Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease
Pagán, F., Wilmarth, B., Torres-Yaghi, Y. A., Hebron, M. L., Mulki, S., Ferrante, D., Matar, S., Ahn, J., & Moussa, C. (2020) · Movement Disorders · doi:10.1002/mds.28389 · Cited by 61 · see citing works
Parkinson's Disease Modification Through Abl Kinase Inhibition: An Opportunity
Werner, M. H., & Olanow, C. W. (2021) · Movement Disorders · doi:10.1002/mds.28858 · Cited by 60 · see citing works
From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology
Toader, C., Dobrin, N., Brehar, F.-M., Popa, C., Covache-Busuioc, R.-A., Glavan, L.-A., Costin, H. P., Bratu, B.-G., Corlatescu, A.-D., Popa, A. A., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216119 · Cited by 61 · see citing works
The Involvement of Neuroinflammation in the Onset and Progression of Parkinson’s Disease
Jurcău, A., Andronie-Cioară, F. L., Nistor-Cseppento, C. D., Pașcalău, N., Rus, M., Vasca, E., & Jurcău, M. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914582 · Cited by 56 · see citing works
New hopes for disease modification in Parkinson's Disease
Poewe, W. H., Seppi, K., Marini, K., & Mahlknecht, P. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108085 · Cited by 51 · see citing works
Approaches to Disease Modification for Parkinson's Disease: Clinical Trials and Lessons Learned
Hung, A. Y., & Schwarzschild, M. A. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00964-w · Cited by 52 · see citing works
Zou, K., Li, Q., Li, D., Jiao, Y., Wang, L., Li, L., Wang, J., Li, Y., Gao, R., Li, F., et al. (2024) · ACS Nano · doi:10.1021/acsnano.3c11641 · Cited by 49 · see citing works
Current Drug Repurposing Strategies for Rare Neurodegenerative Disorders
Shah, S., Dooms, M. M., Amaral‐Garcia, S., & Igoillo‐Esteve, M. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.768023 · Cited by 48 · see citing works
Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers
Kreiser, R. P., Wright, A. K., Block, N. R., Hollows, J. E., Nguyen, L. T., LeForte, K., Mannini, B., Vendruscolo, M., & Limbocker, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228651 · Cited by 47 · see citing works
Discoidin Domain Receptor 1 is a therapeutic target for neurodegenerative diseases
Fowler, A. J., Hebron, M. L., Balaraman, K., Shi, W., Missner, A. A., Greenzaid, J. D., Chiu, T. L., Ullman, C. J., Weatherdon, E., Duka, V., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa177 · Cited by 47 · see citing works
Targeting dementias through cancer kinases inhibition
Fagiani, F., Lanni, C., Racchi, M., & Govoni, S. (2020) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12044 · Cited by 43 · see citing works
In search of an anti-inflammatory drug for Alzheimer disease
Gyengési, E., & Münch, G. W. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-019-0307-9 · Cited by 43 · see citing works
Alpha synuclein post translational modifications: potential targets for Parkinson’s disease therapy?
Brembati, V., Faustini, G., Longhena, F., & Bellucci, A. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1197853 · Cited by 42 · see citing works
Baggett, D., Olson, A., & Parmar, M. S. (2024) · Brain Disorders · doi:10.1016/j.dscb.2024.100163 · Cited by 38 · see citing works
Zhang, X., & Che, C. (2021) · Future Internet · doi:10.3390/fi13010014 · Cited by 37 · see citing works
Advances in dementia with Lewy bodies
Armstrong, M. J. (2021) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864211057666 · Cited by 37 · see citing works
Wu, J., Xu, X., Li, Z., Mo, J., Jin, X., & Bao, Y. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108025 · Cited by 36 · see citing works
Walsh, R. R., Damle, N. K., Mandhane, S. N., Piccoli, S. P., Talluri, R. S., Love, D. K., Yao, S., Ramanathan, V. K., & Hurko, O. (2023) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2023.105281 · Cited by 35 · see citing works
Gibson, L. L., Ruiz, C. A., Chong, J. R., Ballard, C. G., & Aarsland, D. (2023) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001173 · Cited by 35 · see citing works
Parkinson Disease: Translating Insights from Molecular Mechanisms to Neuroprotection
Pirooznia, S. K., Rosenthal, L. S., Dawson, V. L., & Dawson, T. M. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000189 · Cited by 36 · see citing works
Karuppagounder, S. S., Wang, H., Kelly, T., Rush, R., Nguyen, R. Q., Bisen, S. S., Yamashita, Y., Sloan, N., Dang, B., Sigmon, A., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abp9352 · Cited by 35 · see citing works
α‐Synuclein in Parkinson's Disease: From Bench to Bedside
Bellini, G., D’Antongiovanni, V., Palermo, G., Antonioli, L., Fornai, M., Ceravolo, R., Bernardini, N., Derkinderen, P., & Pellegrini, C. (2024) · Medicinal Research Reviews · doi:10.1002/med.22091 · Cited by 36 · see citing works
Therapeutic targeting of Lyn kinase to treat chorea-acanthocytosis
Peikert, K., Federti, E., Mattè, A., Constantin, G., Pietronigro, E. C., Fabene, P. F., Defilippi, P., Turco, E., Gallo, F. D., Pucci, P., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01181-y · Cited by 34 · see citing works
Mitophagy in Parkinson's disease: From pathogenesis to treatment target
Dernie, F. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104756 · Cited by 33 · see citing works
Pharmacological Modulators of Tau Aggregation and Spreading
Dominguez‐Meijide, A., Vasili, E., & Outeiro, T. F. (2020) · Brain Sciences · doi:10.3390/brainsci10110858 · Cited by 34 · see citing works
Angelopoulou, E., Paudel, Y. N., Julian, T. H., Shaikh, M. F., & Piperi, C. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02201-z · Cited by 34 · see citing works
Evolving Landscape of Parkinson’s Disease Research: Challenges and Perspectives
Tenchov, R., Sasso, J. M., & Zhou, Q. A. (2025) · ACS Omega · doi:10.1021/acsomega.4c09114 · Cited by 33 · see citing works
Cancer and Parkinson's Disease: Common Targets, Emerging Hopes
Filippou, P. S., & Outeiro, T. F. (2020) · Movement Disorders · doi:10.1002/mds.28425 · Cited by 30 · see citing works
Drug repurposing strategies of relevance for Parkinson’s disease
Fletcher, E. J. R., Kaminski, T. W., Williams, G. H., & Duty, S. (2021) · Pharmacology Research & Perspectives · doi:10.1002/prp2.841 · Cited by 30 · see citing works
The AKT modulator A-443654 reduces α-synuclein expression and normalizes ER stress and autophagy
Gandelman, M., Dansithong, W., Kales, S. C., Paul, S., Maag, G., Aoyama, E., Zakharov, A. V., Rai, G., Dexheimer, T. S., Whitehill, B. M., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101191 · Cited by 32 · see citing works
Gutiérrez, D. A., Chandía-Cristi, A., Yañez, M. J., Zanlungo, S., & Alvarez, A. R. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.346540 · Cited by 30 · see citing works
Siwecka, N., Saramowicz, K., Galita, G., Rozpędek‐Kamińska, W., & Majsterek, I. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15082051 · Cited by 31 · see citing works
Yañez, M. J., Marín, T., Balboa, E., Klein, A. D., Alvarez, A. R., & Zanlungo, S. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165875 · Cited by 28 · see citing works
CSF MicroRNAs Reveal Impairment of Angiogenesis and Autophagy in Parkinson Disease
Fowler, A. J., Ahn, J., Hebron, M., Chiu, T., Ayoub, R., Mulki, S., Ressom, H., Torres-Yaghi, Y., Wilmarth, B., Pagan, F. L., et al. (2021) · Neurology Genetics · doi:10.1212/nxg.0000000000000633 · Cited by 29 · see citing works
Stevenson, M. E., Varghese, R. S., Hebron, M. L., Liu, X., Ratliff, N., Smith, A., Turner, R. S., & Moussa, C. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02802-0 · Cited by 28 · see citing works
Jiao, F., Meng, L., Du, K., & Li, X. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01195 · Cited by 28 · see citing works
Drug Repurposing for Parkinson’s Disease: The International Linked Clinical Trials experience
Stott, S., Wyse, R. K. H., & Brundin, P. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.653377 · Cited by 27 · see citing works
Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations
Rodriguez‐Porcel, F. E., Wyman‐Chick, K. A., Abdelnour, C., Toledo, J. B., Ferreira, D., Urwyler, P., Weil, R. S., Kane, J. P. M., Pilotto, A., Rongve, A., et al. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00299-w · Cited by 28 · see citing works
Hernández‐Parra, H., Cortés, H., Ávalos‐Fuentes, J. A., Prado-Audelo, M. L. D., Florán, B., Leyva‐Gómez, G., Sharifi‐Rad, J., & Cho, W. C. S. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01612-5 · Cited by 27 · see citing works
Autophagy and Redox Homeostasis in Parkinson’s: A Crucial Balancing Act
Jiménez-Moreno, N., & Lane, J. D. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/8865611 · Cited by 26 · see citing works
Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease
Sanchez-Mirasierra, I., Ghimire, S., Hernández-Díaz, S., & Soukup, S. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.921314 · Cited by 26 · see citing works
Anti-amyloid: An antibody to cure Alzheimer’s or an attitude
Osborne, O., Naranjo, O., Heckmann, B. L., Dykxhoorn, D. M., & Toborek, M. J. (2023) · iScience · doi:10.1016/j.isci.2023.107461 · Cited by 25 · see citing works
Neurodegenerative diseases and cancer: sharing common mechanisms in complex interactions
Rojas, N. G., Cesarini, M., Etcheverry, J. L., Prat, G. A. D., Arciuch, V. G. A., & Gatto, E. M. (2020) · Journal of Integrative Neuroscience · doi:10.31083/j.jin.2020.01.3 · Cited by 25 · see citing works
Disease-Modifying Therapies for Multiple System Atrophy: Where Are We in 2022?
Sidoroff, V., Bower, P., Stefanova, N., Fanciulli, A., Stankovic, I., Poewe, W. H., Seppi, K., Wenning, G. K., & Krismer, F. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-223183 · Cited by 24 · see citing works
Can We Treat Neurodegenerative Proteinopathies by Enhancing Protein Degradation?
Engelender, S., Stefanis, L., Oddo, S., & Bellucci, A. (2022) · Movement Disorders · doi:10.1002/mds.29058 · Cited by 23 · see citing works
Nilotinib in Parkinson's disease: A systematic review and meta-analysis
Xie, X., Yuan, P., Kou, L., Chen, X., Li, J., & Li, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.996217 · Cited by 23 · see citing works
c-Abl activates RIPK3 signaling in Gaucher disease
Yañez, M. J., Campos, F., Marín, T., Klein, A. D., Futerman, A. H., Alvarez, A. R., & Zanlungo, S. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166089 · Cited by 22 · see citing works
Safety, target engagement, and biomarker effects of bosutinib in dementia with Lewy bodies
Pagán, F., Torres-Yaghi, Y. A., Hebron, M. L., Wilmarth, B., Turner, R. S., Matar, S., Ferrante, D., Ahn, J., & Moussa, C. (2022) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12296 · Cited by 21 · see citing works
Prospects for Disease Slowing in Parkinson Disease
Menozzi, E., & Schapira, A. H. V. (2024) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-022124-033653 · Cited by 24 · see citing works
Precision Medicine in Parkinson’s Disease: From Genetic Risk Signals to Personalized Therapy
Straccia, G., Colucci, F., Eleopra, R., & Cilia, R. (2022) · Brain Sciences · doi:10.3390/brainsci12101308 · Cited by 22 · see citing works
Satapathy, T., & Kumar, D. (2024) · Pharmacological Research - Modern Chinese Medicine · doi:10.1016/j.prmcm.2024.100499 · Cited by 20 · see citing works
Recent advances in understanding and treatment of Parkinson’s disease
Tarakad, A., & Jankovic, J. J. (2020) · Faculty Reviews · doi:10.12703/b/9-6 · Cited by 18 · see citing works
Recent Advances in the Treatment of Genetic Forms of Parkinson’s Disease: Hype or Hope?
Cavallieri, F., Cury, R. G., Guimarães, T. G., Fioravanti, V., Grisanti, S., Rossi, J., Monfrini, E., Zedde, M., Fonzo, A. D., Valzania, F., et al. (2023) · Cells · doi:10.3390/cells12050764 · Cited by 18 · see citing works
Wyse, R. K. H., Isaacs, T., Barker, R. A., Cookson, M., Dawson, T. M., Devos, D., Dexter, D. T., Duffen, J., Federoff, H. J., Fiske, B. K., et al. (2024) · Journal of Parkinson s Disease · doi:10.3233/jpd-230363 · Cited by 19 · see citing works
Therapeutic innovation in Parkinson’s disease: a 2020 update on disease-modifying approaches
Colombo, D., Pnevmatikou, P., Melloni, E., & Keywood, C. (2020) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2020.1800454 · Cited by 17 · see citing works
Majumdar, M., & Badwaik, H. R. (2024) · Current Drug Targets · doi:10.2174/0113894501312703240826070530 · Cited by 16 · see citing works
Prioritizing Parkinson’s disease risk genes in genome-wide association loci
Lange, L. M., Cerquera‐Cleves, C., Schipper, M., Panagiotaropoulou, G., Braun, A., Kraft, J., Awasthi, S., Bell, N., Posthuma, D., Ripke, S., et al. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-00933-0 · Cited by 18 · see citing works
O'Brien, J. T., Chouliaras, L., Sultana, J., Taylor, J., Ballard, C. G., on behalf of the RENEWAL Study Group, Aarsland, D., Blanc, F., Boeve, B. F., Brooks, D. J., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01103-7 · Cited by 16 · see citing works
Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington’s Disease Patients
Anderson, K. E., Stevenson, M. E., Varghese, R. S., Hebron, M. L., Koppel, E., McCartin, M., Kuprewicz, R., Matar, S., Ferrante, D., & Moussa, C. (2022) · Metabolites · doi:10.3390/metabo12121225 · Cited by 16 · see citing works
Lenka, A., & Jankovic, J. J. (2023) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2023.2177535 · Cited by 16 · see citing works
Min, Y., Wang, X., İş, Ö., Patel, T., Gao, J., Reddy, J. S., Quicksall, Z., Nguyen, T., Lin, S., Tutor‐New, F. Q., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42626-3 · Cited by 20 · see citing works
The Role of Kinases in Neurodegenerative Diseases: From Pathogenesis to Treatment
Naim, A., Farooqui, A. M., Badruddeen, B., Khan, M. I., Akhtar, J., Ahmad, A., & Islam, A. (2025) · European Journal of Neuroscience · doi:10.1111/ejn.70156 · Cited by 15 · see citing works
Das, V., Miller, J. H., Goud, A. C., Annadurai, N., Sanctis, J. B. D., Hrubá, L., & Hajdúch, M. (2024) · Medicinal Research Reviews · doi:10.1002/med.22033 · Cited by 15 · see citing works
Seeking progress in disease modification in Parkinson disease
Lungu, C., Cedarbaum, J. M., Dawson, T. M., Dorsey, E. R., Faraco, C., Federoff, H. J., Fiske, B. K., Fox, R. J., Goldfine, A. M., Kieburtz, K. D., et al. (2021) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2021.09.006 · Cited by 15 · see citing works
Min, H. K., Kim, S. H., Won, J., Kim, K., Lee, J., Lee, S., & Kim, H. (2023) · International Journal of Rheumatic Diseases · doi:10.1111/1756-185x.14627 · Cited by 15 · see citing works
Wilkes, B. J., Tobin, E. R., Arpin, D. J., Wang, W., Okun, M. S., Jaffee, M. S., McFarland, N. R., Corcos, D. M., & Vaillancourt, D. E. (2023) · npj Parkinson s Disease · doi:10.1038/s41531-023-00521-0 · Cited by 14 · see citing works
Insights into the management of Lewy body dementia: a scoping review
Khan, S. A., Khan, S., Kausar, H., Shah, R. K., Luitel, A., Gautam, S., Parajuli, S. B., Rauniyar, V. K., & Khan, M. A. (2024) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000001664 · Cited by 14 · see citing works
Dementia with Lewy bodies: emerging drug targets and therapeutics
Pope, E. D., Cordes, L., Shi, J., Mari, Z. K., Decourt, B., & Sabbagh, M. N. (2021) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2021.1916913 · Cited by 14 · see citing works
Targeting Lyn Kinase in Chorea-Acanthocytosis: A Translational Treatment Approach in a Rare Disease
Peikert, K., Glaß, H., Federti, E., Mattè, A., Pelzl, L., Akgün, K., Ziemssen, T., Ordemann, R., Lang, F. J. W., Franceschi, L. D., et al. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11050392 · Cited by 14 · see citing works
Espay, A. J., Hauser, R. A., & Armstrong, M. J. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.3983 · Cited by 14 · see citing works
Parkinson's disease: pathogenesis and therapeutic strategies
Zhang, S., Wang, T., Peng, Y., Wang, Q., Zhang, Z., Shifeng, C. H. U., Huang, H., & Chen, N. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00445-0 · Cited by 13 · see citing works
Drug Repositioning and Repurposing for Disease-Modifying Effects in Parkinson’s Disease
Jeong, S. H., & Lee, P. H. (2025) · Journal of Movement Disorders · doi:10.14802/jmd.25008 · Cited by 13 · see citing works
Pharmacological management of Parkinson’s disease in older people
Mouchaileh, N., & Hughes, A. J. (2020) · Journal of Pharmacy Practice and Research · doi:10.1002/jppr.1683 · Cited by 13 · see citing works
Yan, H., Huang, X., Xu, J., Zhang, Y., Chen, J., Xu, Z., Li, H., Wang, Z., Yang, X., Yang, B., et al. (2023) · Advanced Science · doi:10.1002/advs.202302002 · Cited by 13 · see citing works
A Novel, Selective c-Abl Inhibitor, Compound 5, Prevents Neurodegeneration in Parkinson’s Disease
Kwon, S., Kim, S., Park, A. Y., Lee, S., Gadhe, C. G., Seo, B. A., Park, J. S., Jo, S., Oh, Y., Kweon, S. H., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01022 · Cited by 13 · see citing works
Lillian, A., Zuo, W., Laham, L., Hilfiker, S., & Ye, J.-H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087186 · Cited by 12 · see citing works
Stevenson, M. E., Algarzae, N. K., & Moussa, C. (2024) · Frontiers in Dementia · doi:10.3389/frdem.2024.1458038 · Cited by 12 · see citing works
Skin Cancer May Delay Onset but Not Progression of Parkinson's Disease: A Nested Case-Control Study
Mahajan, A., Chirra, M., Dwivedi, A. K., Sturchio, A., Keeling, E. G., Marsili, L., & Espay, A. J. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00406 · Cited by 12 · see citing works
Khan, M. A., Haider, N., Singh, T., Bandopadhyay, R., Ghoneim, M. M., Alshehri, S., Taha, M., Ahmad, J., & Mishra, A. (2023) · Metabolic Brain Disease · doi:10.1007/s11011-023-01180-z · Cited by 12 · see citing works
Bashir, B., Vishwas, S., Gupta, G., Paudel, K. R., Dureja, H., Kumar, P., Cho, H., Sugandhi, V. V., Kumbhar, P., Disouza, J., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102693 · Cited by 11 · see citing works
Mutant-Huntingtin Molecular Pathways Elucidate New Targets for Drug Repurposing
Makeeva, V. S., Dyrkheeva, N. S., Lavrik, O. I., Zakian, S. M., & Malakhova, A. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316798 · Cited by 11 · see citing works
Chandía-Cristi, A., Gutiérrez, D. A., Dulcey, A. E., Lara, M., Vargas, L., Lin, Y.-H., Jimenez-Muñoz, P., Larenas, G., Xu, X., Wang, A. Y., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114144 · Cited by 9 · see citing works
- Authors
- Pagan, F. L., Hebron, M. L., Wilmarth, B., Torres-Yaghi, Y., Lawler, A., Mundel, E. E., Yusuf, N., Starr, N. J., Anjum, M., Arellano, J., Howard, H. H., Shi, W., Mulki, S., Kurd-Misto, T., Matar, S., Liu, X., Ahn, J., & Moussa, C.
- Affiliations
- Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Washington, DC
- Georgetown University Medical Center (US)
- MedStar Georgetown University Hospital (US)
- Corresponding author
- Moussa, Charbel
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2020-03-01
- Volume
- 77
- Issue
- 3
- Pages
- 309
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC6990742
- OpenAlex
- W2995537689
- Cited by
- 185
- References
- 32
- Citations by year
- 2026: 18 · 2025: 18 · 2024: 35 · 2023: 29 · 2022: 28 · 2021: 30 · 2020: 26 · 2019: 1
- FWCI
- 14.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- JAMA Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- nilotinib, Parkinson's disease, disease-modifying therapy, safety and tolerability, pharmacokinetics, cerebrospinal fluid biomarkers, homovanillic acid, DOPAC, dopamine metabolism, adverse events, dose comparison, washout
- MeSH terms
- Aged, Dopamine, Double-Blind Method, Female, Humans, Male, Middle Aged, Parkinson Disease, Pyrimidines, Biomarkers, tau Proteins
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