Effect of lovastatin on behavior in children and adults with fragile X syndrome: An open‐label study
Abstract
Fragile X syndrome (FXS) results from dynamic mutations leading ultimately to the absence of expression of the Fragile X Mental Retardation Protein (FMRP). It is characterized by synaptic upregulated protein synthesis and immature dendritic spines associated with altered brain plasticity and cognitive functions. Recent work in Fmr1 knockout mice has shown that lovastatin, an inhibitor of Ras‐ERK1/2, normalized hippocampus protein synthesis. We hypothesize that lovastatin, as a disease‐modifying drug, would counterweigh the absence of FMRP and improve behavior. Here we report a phase I study to assess the safety and efficacy of lovastatin in individuals with FXS. A total of 15 patients (13 males, 6–31 years old) were treated with escalating doses of lovastatin (up to 40 mg) for three months. Their behavior were assessed before and after treatment using the Aberrant Behavioral Checklist—Community (ABC‐C) total score (primary outcome), as well as domains of the FXS validated version of the ABC‐C (secondary outcomes). The treatment was well tolerated and minimal side effects were reported. Significant improvement in the primary outcome ( P < 0.005), as well as in secondary outcomes, were observed in the majority of the subjects (12/15). We think that long‐term sustained treatment with diseased‐modifying drugs would be necessary in order to improve behavior and ultimately learning. Lovastatin, well known for its long‐term security profile, would be a good candidate for that purposes. Our study showing reassuring safety data along with potential functional benefit emphasizes the need of a placebo‐controlled trial to ascertain lovastatin efficacy in FXS individuals. © 2014 Wiley Periodicals, Inc.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Statin treatment might improve behavioral outcomes in FXS children and lovastatin has beneficial effects on the phenotype of Fmr1 KO mice.
“Statin treatment might improve behavioral outcomes in FXS children16,17 and lovastatin has beneficial effects on the phenotype of Fmr1 KO mice14.”
From An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis (2023) · cites this paper as [16]
Cites
Verkerk, A. J. M. H., Pieretti, M., Sutcliffe, J. S., Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Reiner, O., Richards, S., Victoria, M. F., Zhang, F., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90397-h · Cited by 3,481 · see citing works
The mGluR theory of fragile X mental retardation
Bear, M. F., Huber, K. M., & Warren, S. T. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.04.009 · Cited by 1,580 · see citing works
Statin Safety: A Systematic Review
Law, M., & Rudnicka, A. R. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.12.010 · Cited by 808 · see citing works
Jacquemont, S., Curie, A., des Portes, V., Torrioli, M. G., Berry-Kravis, E., Hagerman, R. J., Ramos, F. J., Cornish, K., He, Y., Paulding, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001708 · Cited by 609 · see citing works
Osterweil, E. K., Krueger, D. D., Reinhold, K., & Bear, M. F. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3888-10.2010 · Cited by 384 · see citing works
Statin Safety: An Overview and Assessment of the Data—2005
Bays, H. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.12.006 · Cited by 264 · see citing works
Osterweil, E. K., Chuang, S.-C., Chubykin, A. A., Sidorov, M., Bianchi, R., Wong, R. K. S., & Bear, M. F. (2013) · Neuron · doi:10.1016/j.neuron.2012.01.034 · Cited by 230 · see citing works
Open-label add-on treatment trial of minocycline in fragile X syndrome.
Paribello, C., Tao, L., Folino, A., Berry-Kravis, E., Tranfaglia, M., Ethell, I. M., & Ethell, D. W. (2010) · BMC Neurology · doi:10.1186/1471-2377-10-91 · Cited by 223 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.65 · Cited by 838 · see citing works
Asiminas, A., Jackson, A. D., Louros, S. R., Till, S. M., Spano, T., Dando, O., Bear, M. F., Chattarji, S., Hardingham, G. E., Osterweil, E. K., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aao0498 · Cited by 78 · see citing works
Lovastatin, Not Simvastatin, Corrects Core Phenotypes in the Fragile X Mouse Model
Muscas, M., Louros, S. R., & Osterweil, E. K. (2019) · eneuro · doi:10.1523/eneuro.0097-19.2019 · Cited by 30 · see citing works
Certainty of genuine treatment increases drug responses among intellectually disabled patients
Jensen, K. B., Kirsch, I., Pontén, M., Rosén, A., Yang, K., Gollub, R. L., des Portes, V., Kaptchuk, T. J., & Curie, A. (2017) · Neurology · doi:10.1212/wnl.0000000000003934 · Cited by 17 · see citing works
An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis
Talvio, K., Wagner, V. A., Minkeviciene, R., Kirkwood, J. S., Kulinich, A. O., Umemori, J., Bhatia, A., Hur, M., Käkelä, R., Ethell, I. M., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-05147-9 · Cited by 8 · see citing works
“This pathway is targeted in FXS preclinical studies (5-7) and clinical trials (8-10) by administering”
BackgroundAstrocytes in fragile X syndrome
Talvio, K., & Castrén, M. L. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1322541 · Cited by 8 · see citing works
- Authors
- Çaku, A., Pellerin, D., Bouvier, P., Riou, E., & Corbin, F.
- Affiliations
- Université de Sherbrooke (CA)
- Department of Pediatrics Faculty of Medicine and Health Sciences Université de Sherbrooke Sherbrooke Québec Canada
- Department of Biochemistry Faculty of Medicine and Health Sciences Université de Sherbrooke Sherbrooke Québec Canada
- Venue
- American Journal of Medical Genetics Part A
- Publisher
- Wiley
- Published
- 2014-09-24
- Volume
- 164
- Issue
- 11
- Pages
- 2834-2842
- ISSN
- 1552-4825 (ISSN-L)
- 1552-4833
- OpenAlex
- W2023366466
- Cited by
- 77
- References
- 8
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 12 · 2019: 9 · 2018: 4 · 2017: 15 · 2016: 4 · 2015: 6
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part A (publishedVersion)
- PubMed (publishedVersion)
- Funders
- FRAXA Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Keywords
- lovastatin, fragile X syndrome, FMRP, aberrant behavior, disease-modifying therapy, drug safety, statins, synaptic protein synthesis, children and adults
- MeSH terms
- Adolescent, Adult, Behavior, Child, Female, Fragile X Syndrome, Humans, Lovastatin, Male, Mutation, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Fragile X Messenger Ribonucleoprotein 1, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
