Repurposing available drugs for neurodevelopmental disorders: The fragile X experience

Neuropharmacology

Volumn 147, Issue , 2019, Pages 74-86

  Tranfaglia, Michael R ^a   Thibodeaux, Clare ^b   Mason, Daniel J ^c   Brown, David ^c   Roberts, Ian ^c   Smith, Richard ^c   Guilliams, Tim ^c   Cogram, Patricia ^d,e,f  

^a FRAXA Research Foundation   (United States)

^b Cures within Reach   (United States)

^c Healx Ltd   (United Kingdom)

^d INSTITUTO DE ECOLOGÍA Y BIODIVERSIDAD IEB   (Chile)

^e FAVALORO UNIVERSITY   (Argentina)

^f UNIVERSITY OF CHILE   (Chile)

Author keywords

[No Author keywords available]

Indexed keywords

ACAMPROSATE; ALPHA TOCOPHEROL; ARBACLOFEN; ASCORBIC ACID; ATOMOXETINE; BACLOFEN; BUMETANIDE; DISULFIRAM; DONEPEZIL; EPIGALLOCATECHIN GALLATE; FENFLURAMINE; FOLIC ACID; GUANFACINE; LITHIUM; MEMANTINE; METFORMIN; METOPROLOL; MEVINOLIN; MINOCYCLINE; OXYTOCIN; PHENFORMIN; PLACEBO; QUERCETIN; RILUZOLE; SERTRALINE; SULINDAC; TETRABENAZINE; TOPIRAMATE; UNINDEXED DRUG; VALPROIC ACID; ZOGENIX;

ATTENTION DEFICIT DISORDER; AUTISM; COMPUTER MODEL; DRUG DEVELOPMENT; DRUG MECHANISM; DRUG MEGADOSE; DRUG REPOSITIONING; EXPERIMENTAL ANIMAL; FEAR CONDITIONING TEST; FRAGILE X SYNDROME; GENE EXPRESSION; GENE EXPRESSION PROFILING; GILLES DE LA TOURETTE SYNDROME; HUMAN; MACHINE LEARNING; MENTAL DISEASE; MICROARRAY ANALYSIS; NESTING; NONHUMAN; OPEN FIELD TEST; PRECLINICAL STUDY; PRIORITY JOURNAL; REVIEW; SEVERE MYOCLONIC EPILEPSY IN INFANCY; SOCIAL INTERACTION; STATISTICAL ANALYSIS; TRANSCRIPTOMICS; ANIMAL; DRUG EFFECT; MOTOR ACTIVITY; RANDOMIZED CONTROLLED TRIAL (TOPIC);

ANIMALS; DISULFIRAM; DRUG REPOSITIONING; FRAGILE X SYNDROME; HUMANS; METOPROLOL; MINOCYCLINE; MOTOR ACTIVITY; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SULINDAC;

EID: 85061943285     PISSN: 00283908     EISSN: 18737064     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2018.05.004     Document Type: Review

References (90)

1. Anderson, S.L., Liu, B., Qiu, J., Sturm, A.J., Schwartz, J.A., Peters, A.J., Sullivan, K.A., Rubin, B.Y., Nutraceutical-mediated restoration of wild-type levels of IKBKAP-encoded IKAP protein in familial dysautonomia-derived cells. Mol. Nutr. Food Res. 56 (2012), 570–579.
2. Berry-Kravis, E., Hagerman, R., Visootsak, J., Budimirovic, D., Kaufmann, W.E., Cherubini, M., Zarevics, P., Walton-Bowen, K., Wang, P., Bear, M.F., Carpenter, R.L., J. Neurodev. Disord., 9(3), 2017 Jun 12, 10.1186/s11689-016-9181-6 PMID:28616094.
3. Berry-Kravis, E., Levin, R., Shah, H., Mathur, S., Darnell, J.C., Ouyang, B., Cholesterol levels in fragile X syndrome. Am. J. Med. Genet. 167A:2 (2015 Feb), 379–384, 10.1002/ajmg.a.36850 PMID:25424470.
4. Berry-Kravis, E., Sumis, A., Hervey, C., Nelson, M., Porges, S.W., Weng, N., Weiler, I.J., Greenough, W.T., Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J. Dev. Behav. Pediatr. 29:4 (2008 Aug), 293–302, 10.1097/DBP.0b013e31817dc447 PMID:18698192.
5. Berry-Kravis, E.M., Hessl, D., Rathmell, B., Zarevics, P., Cherubini, M., Walton-Bowen, K., Mu, Y., Nguyen, D.V., Gonzalez-Heydrich, J., Wang, P.P., Carpenter, R.L., Bear, M.F., Hagerman, R.J., Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial. Sci. Transl. Med., 4(152), 2012 Sep 19 152ra127. PMID:22993294.
6. Bilousova, T.V., Dansie, L., Ngo, M., Aye, J., Charles, J.R., Ethell, D.W., Ethell, I.M., Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J. Med. Genet. 46:2 (2009 Feb), 94–102, 10.1136/jmg.2008.061796 PMID:18835858.
7. Boone, K.M., Gracious, B., Klebanoff, M.A., Rogers, L.K., Rausch, J., Coury, D.L., Keim, S.A., Omega-3 and -6 fatty acid supplementation and sensory processing in toddlers with ASD symptomology born preterm: a randomized controlled trial. Early Hum. Dev. 115 (2017), 64–70.
8. Bride, K.L., Vincent, T., Smith-Whitley, K., Lambert, M.P., Bleesing, J.J., Seif, A.E., Manno, C.S., Casper, J., Grupp, S.A., Teachey, D.T., Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood 127 (2016), 17–28.
9. Brown, V., Jin, P., Ceman, S., Darnell, J.C., O'Donnell, W.T., Tenenbaum, S.A., Jin, X., Feng, Y., Wilkinson, K.D., Keene, J.D., Darnell, R.B., Warren, S.T., Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107:4 (2001 Nov 16), 477–487 PMID:11719188.
10. Brown, W.T., Cohen, I.L., Fisch, G.S., Wolf-Schein, E.G., Jenkins, V.A., Malik, M.N., Jenkins, E.C., High dose folic acid treatment of fragile (X) males. Am. J. Med. Genet. 23:1–2 (1986 Jan-Feb), 263–271 PMID:3513568.
11. Caban, A., Pisarczyk, K., Kopacz, K., Kapuśniak, A., Toumi, M., Rémuzat, C., Kornfeld, A., Filling the gap in CNS drug development: evaluation of the role of drug repurposing. J. Mark Acc. Health Pol., 5, 2017, 10.1080/20016689.2017.1299833 published online at.
12. Çaku, A., Pellerin, D., Bouvier, P., Riou, E., Corbin, F., Effect of lovastatin on behavior in children and adults with fragile X syndrome: an open-label study. Am. J. Med. Genet. 164A:11 (2014 Nov), 2834–2842, 10.1002/ajmg.a.36750 PMID:25258112.
13. Castagnola, S., Bardoni, B., Maurin, T., The search for an effective therapy to treat fragile X syndrome: dream or reality?. Front. Synaptic Neurosci., 9(15), 2017 Nov 6, 10.3389/fnsyn.2017.00015 Review. PMID:29163124.
14. Ceulemans, B., Schoonjans, A.S., Marchau, F., Paelinck, B.P., Lagae, L., Five-year extended follow-up status of 10 patients with Dravet syndrome treated with fenfluramine. Epilepsia 57 (2016), e129–e134.
15. Chen, L., Toth, M., Fragile X mice develop sensory hyperreactivity to auditory stimuli. Neuroscience 103:4 (2001), 1043–1050 PMID:11301211.
16. Choi, C.H., Schoenfeld, B.P., Bell, A.J., Hinchey, J., Rosenfelt, C., Gertner, M.J., Campbell, S.R., Emerson, D., Hinchey, P., Kollaros, M., Ferrick, N.J., Chambers, D.B., Langer, S., Sust, S., Malik, A., Terlizzi, A.M., Liebelt, D.A., Ferreiro, D., Sharma, A., Koenigsberg, E., Choi, R.J., Louneva, N., Arnold, S.E., Featherstone, R.E., Siegel, S.J., Zukin, R.S., McDonald, T.V., Bolduc, F.V., Jongens, T.A., McBride, S.M., Multiple drug treatments that increase cAMP signaling restore long-term memory and aberrant signaling in fragile X syndrome models. Front. Behav. Neurosci., 10, 2016 Jun 30, 136, 10.3389/fnbeh.2016.00136 PMID:27445731.
17. Choi, C.H., Schoenfeld, B.P., Bell, A.J., Hinchey, P., Kollaros, M., Gertner, M.J., Woo, N.H., Tranfaglia, M.R., Bear, M.F., Zukin, R.S., McDonald, T.V., Jongens, T.A., McBride, S.M., Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment. Brain Res. 1380 (2011 Mar 22), 106–119, 10.1016/j.brainres.2010.11.032 PMID:21078304.
18. Choi, C.H., Schoenfeld, B.P., Weisz, E.D., Bell, A.J., Chambers, D.B., Hinchey, J., Choi, R.J., Hinchey, P., Kollaros, M., Gertner, M.J., Ferrick, N.J., Terlizzi, A.M., Yohn, N., Koenigsberg, E., Liebelt, D.A., Zukin, R.S., Woo, N.H., Tranfaglia, M.R., Louneva, N., Arnold, S.E., Siegel, S.J., Bolduc, F.V., McDonald, T.V., Jongens, T.A., McBride, S.M.J., PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome. J. Neurosci. 35 (2015), 396–408, 10.1523/JNEUROSCI.1356-12.2015.
19. Cohen, I.L., Tsiouris, J.A., Pfadt, A., Effects of long-acting propranolol on agonistic and stereotyped behaviors in a man with pervasive developmental disorder and fragile X syndrome: a double-blind, placebo-controlled study. J. Clin. Psychopharmacol. 11 (1991), 398–399.
20. Cook-Sather, S.D., Viola, L., Zur, K.B., Rubin, B.Y., Case scenario: perioperative administration of tocotrienols and green tea extract in a child with familial dysautonomia. Anesthesiology 117 (2012), 639–645.
21. Dansie, L.E., Phommahaxay, K., Okusanya, A.G., Uwadia, J., Huang, M., Rotschafer, S.E., Razak, K.A., Ethell, D.W., Ethell, I.M., Long-lasting effects of minocycline on behavior in young but not adult Fragile X mice. Neuroscience 246 (2013 Aug 29), 186–198, 10.1016/j.neuroscience.2013.04.058 PMID:23660195.
22. Darnell, J.C., Jensen, K.B., Jin, P., Brown, V., Warren, S.T., Darnell, R.B., Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107:4 (2001 Nov 16), 489–499 PMID:11719189.
23. de Diego-Otero, Y., Calvo-Medina, R., Quintero-Navarro, C., Sánchez-Salido, L., García-Guirado, F., del Arco-Herrera, I., Fernández-Carvajal, I., Ferrando-Lucas, T., Caballero-Andaluz, R., Pérez-Costillas, L., A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial. Trials, 15, 2014 Sep 3, 345, 10.1186/1745-6215-15-345 PMID:25187257.
24. de Diego-Otero, Y., Romero-Zerbo, Y., el Bekay, R., Decara, J., Sanchez, L., Rodriguez-de Fonseca, F., del Arco-Herrera, I., Alpha-tocopherol protects against oxidative stress in the fragile X knockout mouse: an experimental therapeutic approach for the Fmr1 deficiency. Neuropsychopharmacology 34:4 (2009 Mar), 1011–1026, 10.1038/npp.2008.152 PMID:18843266.
25. de la Hoz, B., Soria, C., Fraj, J., Losada, E., Ledo, A., Fixed drug eruption due to piroxicam. Int. J. Dermatol. 29 (1990), 672–673.
26. Dy, A.B.C., Tassone, F., Eldeeb, M., Salcedo-Arellano, M.J., Tartaglia, N., Hagerman, R., Metformin as targeted treatment in fragile X syndrome. Clin. Genet., 2017 Apr 24, 10.1111/cge.13039 PMID:28436599.
27. Dziembowska, M., Pretto, D.I., Janusz, A., Kaczmarek, L., Leigh, M.J., Gabriel, N., Durbin-Johnson, B., Hagerman, R.J., Tassone, F., High MMP-9 activity levels in fragile X syndrome are lowered by minocycline. Am. J. Med. Genet. 161A:8 (2013 Aug), 1897–1903, 10.1002/ajmg.a.36023 PMID:23824974.
28. el Bekay, R., Romero-Zerbo, Y., Decara, J., Sanchez-Salido, L., Del Arco-Herrera, I., Rodríguez-de Fonseca, F., de Diego-Otero, Y., Enhanced markers of oxidative stress, altered antioxidants and NADPH-oxidase activation in brains from Fragile X mental retardation 1-deficient mice, a pathological model for Fragile X syndrome. Eur. J. Neurosci. 26:11 (2007 Dec), 3169–3180 PMID:18005058.
29. Erickson, C.A., Mullett, J.E., McDougle, C.J., Brief report: acamprosate in fragile X syndrome. J. Autism Dev. Disord. 40:11 (2010 Nov), 1412–1416, 10.1007/s10803-010-0988-9 PMID:20213249.
30. Erickson, C.A., Mullett, J.E., McDougle, C.J., Open-label memantine in fragile X syndrome. J. Autism Dev. Disord. 39:12 (2009 Dec), 1629–1635, 10.1007/s10803-009-0807-3 PMID:19609663.
31. Erickson, C.A., Ray, B., Maloney, B., Wink, L.K., Bowers, K., Schaefer, T.L., McDougle, C.J., Sokol, D.K., Lahiri, D.K., Impact of acamprosate on plasma amyloid-β precursor protein in youth: a pilot analysis in fragile X syndrome-associated and idiopathic autism spectrum disorder suggests a pharmacodynamic protein marker. J. Psychiatr. Res. 59 (2014 Dec), 220–228, 10.1016/j.jpsychires.2014.07.011 PMID:25300441.
32. Erickson, C.A., Weng, N., Weiler, I.J., Greenough, W.T., Stigler, K.A., Wink, L.K., McDougle, C.J., Open-label riluzole in fragile X syndrome. Brain Res. 1380 (2011 Mar 22), 264–270, 10.1016/j.brainres.2010.10.108 PMID:21059347.
33. Erickson, C.A., Wink, L.K., Ray, B., Early, M.C., Stiegelmeyer, E., Mathieu-Frasier, L., Patrick, V., Lahiri, D.K., McDougle, C.J., Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. Psychopharmacology (Berlin) 228:1 (2013 Jul), 75–84, 10.1007/s00213-013-3022-z PMID:23436129.
34. Fisch, G.S.1, Cohen, I.L., Gross, A.C., Jenkins, V., Jenkins, E.C., Brown, W.T., Folic acid treatment of fragile X males: a further study. Am. J. Med. Genet., 30(1–2), 1988 May-Jun 393–9. PMID:3052065.
35. Froster-Iskenius, U., Bödeker, K., Oepen, T., Matthes, R., Piper, U., Schwinger, E., Folic acid treatment in males and females with fragile-(X)-syndrome. Am. J. Med. Genet. 23:1–2 (1986 Jan-Feb), 273–289 PMID:3513569.
36. Gantois, I., Khoutorsky, A., Popic, J., Aguilar-Valles, A., Freemantle, E., Cao, R., Sharma, V., Pooters, T., Nagpal, A., Skalecka, A., Truong, V.T., Wiebe, S., Groves, I.A., Jafarnejad, S.M., Chapat, C., McCullagh, E.A., Gamache, K., Nader, K., Lacaille, J.C., Gkogkas, C.G., Sonenberg, N., Metformin ameliorates core deficits in a mouse model of fragile X syndrome. Nat. Med. 23:6 (2017 Jun), 674–677, 10.1038/nm. 4335 PMID:28504725.
37. Gillberg, C., Wahlström, J., Johansson, R., Törnblom, M., Albertsson-Wikland, K., Folic acid as an adjunct in the treatment of children with the autism fragile-X syndrome (AFRAX). Dev. Med. Child Neurol. 28:5 (1986 Oct), 624–627 PMID:3536640.
38. Global Genes. Rare Disease: Facts and Statistics. https://globalgenes.org/rare-diseases-facts-statistics/.
39. Greiss Hess, L., Fitzpatrick, S.E., Nguyen, D.V., Chen, Y., Gaul, K.N., Schneider, A., Lemons Chitwood, K., Eldeeb, M.A., Polussa, J., Hessl, D., Rivera, S., Hagerman, R.J., A randomized, double-blind, placebo-controlled trial of low-dose sertraline in young children with fragile X syndrome. J. Dev. Behav. Pediatr. 37:8 (2016 Oct), 619–628 PMID: 27560971.
40. Hagerman, R.J., Jackson, A.W., Levitas, A., Braden, M., McBogg, P., Kemper, M., McGavran, L., Berry, R., Matus, I., Hagerman, P.J., Oral folic acid versus placebo in the treatment of males with the fragile X syndrome. Am. J. Med. Genet. 23:1–2 (1986 Jan-Feb), 241–262 Review. PMID:3513567.
41. Hagerman, R.J., Polussa, J., Treatment of the psychiatric problems associated with fragile X syndrome. Curr. Opin. Psychiatr. 28:2 (2015 Mar), 107–112 PMID:25602250.
42. Halevy, T., Czech, C., Benvenisty, N., Molecular mechanisms regulating the defects in fragile X syndrome neurons derived from human pluripotent stem cells. Stem Cell. Rep. 4 (2015), 37–46, 10.1016/j.stemcr.2014.10.015.
43. Hall, S.S., Lightbody, A.A., McCarthy, B.E., Parker, K.J., Reiss, A.L., Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome. Psychoneuroendocrinology 37:4 (2012 Apr), 509–518, 10.1016/j.psyneuen.2011.07.020 PMID:21862226.
44. Henderson, C., Wijetunge, L., Kinoshita, M.N., Shumway, M., Hammond, R.S., Postma, F.R., Brynczka, C., Rush, R., Thomas, A., Paylor, R., Warren, S.T., Vanderklish, P.W., Kind, P.C., Carpenter, R.L., Bear, M.F., Healy, A.M., Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABAB receptors with arbaclofen. Sci. Transl. Med., 4(152), 2012 Sep 19 152ra128. PMID:22993295.
45. Hu, H., Qin, Y., Bochorishvili, G., Zhu, Y., van Aelst, L., Zhu, J.J., Ras signaling mechanisms underlying impaired GluR1-dependent plasticity associated with fragile X syndrome. J. Neurosci. 28:31 (2008 Jul 30), 7847–7862, 10.1523/JNEUROSCI.1496-08.2008 PMID:18667617.
46. Jin, P., Warren, S.T., Understanding the molecular basis of fragile X syndrome. Hum. Mol. Genet. 9 (2000), 901–908, 10.1093/hmg/9.6.901.
47. Kast, R.E., Halatsch, M.-E., Matrix metalloproteinase-2 and -9 in glioblastoma: a trio of old drugs-captopril, disulfiram and nelfinavir-are inhibitors with potential as adjunctive treatments in glioblastoma. Arch. Med. Res. 43 (2012), 243–247, 10.1016/j.arcmed.2012.04.005.
48. Kesler, S.R., Lightbody, A.A., Reiss, A.L., Cholinergic dysfunction in fragile X syndrome and potential intervention: a preliminary 1H MRS study. Am. J. Med. Genet. 149A:3 (2009 Mar), 403–407, 10.1002/ajmg.a.32697 PMID:19215057.
49. Kim, S.H., Markham, J.A., Weiler, I.J., Greenough, W.T., Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome. Proc. Natl. Acad. Sci. U. S. A. 105:11 (2008 Mar 18), 4429–4434, 10.1073/pnas.0800257105 PMID:18332424.
50. Kong, S.W., Sahin, M., Collins, C.D., Wertz, M.H., Campbell, M.G., Leech, J.D., Krueger, D., Bear, M.F., Kunkel, L.M., Kohane, I.S., Divergent dysregulation of gene expression in murine models of fragile X syndrome and tuberous sclerosis. Mol. Autism., 5, 2014, 16, 10.1186/2040-2392-5-16.
51. Korb, E., Herre, M., Zucker-Scharff, I., Gresack, J., Allis, C.D., Darnell, R.B., Excess translation of epigenetic regulators contributes to fragile X syndrome and is alleviated by Brd4 inhibition. Cell 170:6 (2017 Sep 7), 1209–1223, 10.1016/j.cell.2017.07.033 PMID:28823556.
52. Kuleshov, M.V., Jones, M.R., Rouillard, A.D., Fernandez, N.F., Duan, Q., Wang, Z., Koplev, S., Jenkins, S.L., Jagodnik, K.M., Lachmann, A., McDermott, M.G., Monteiro, C.D., Gundersen, G.W., Ma'ayan, A., Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 44 (2016), W90–W97, 10.1093/nar/gkw377.
53. Lagae, L., Sullivan, J., Cross, J.H., Farfel, G.M., Galer, B.S., Gammaitoni, A., Guerrini, R., Knupp, K.G., Laux, L.C., Miller, I., Mistry, A., Morrison, G., Devinsky, O., Nikanorova, M., Polster, T., Talwar, D., Lock, M., Ceulemans, B., ZX008 (Fenfluramine HCl Oral Solution) in Dravet Syndrome: Results of a Phase 3, Randomized, Double-blind, Placebo-controlled Trial. 2017 Poster Presentation http://www.zogenix.com/c/newsroom/publications-presentations.php.
54. Lee, H.M., Kim, Y., Drug repurposing is a new opportunity for developing drugs against neuropsychiatric disorders. Schizophr. Res. Treat., 2016, 2016 12 pages.
55. Leigh, M.J., Nguyen, D.V., Mu, Y., Winarni, T.I., Schneider, A., Chechi, T., Polussa, J., Doucet, P., Tassone, F., Rivera, S.M., Hessl, D., Hagerman, R.J., A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome. J. Dev. Behav. Pediatr. 34:3 (2013 Apr), 147–155, 10.1097/DBP.0b013e318287cd17 PMID:23572165.
56. Liu, Z.H., Chuang, D.M., Smith, C.B., Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome. Int. J. Neuropsychopharmacol. 14:5 (2011 Jun), 618–630, 10.1017/S1461145710000520 PMID:20497624.
57. Liu, Z.H., Huang, T., Smith, C.B., Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome. Neurobiol. Dis. 45:3 (2012 Mar), 1145–1152, 10.1016/j.nbd.2011.12.037 PMID:22227453.
58. McBride, S.M., Choi, C.H., Wang, Y., Liebelt, D., Braunstein, E., Ferreiro, D., Sehgal, A., Siwicki, K.K., Dockendorff, T.C., Nguyen, H.T., McDonald, T.V., Jongens, T.A., Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron 45:5 (2005 Mar 3), 753–764 PMID:15748850.
59. Mientjes, E.J., Nieuwenhuizen, I., Kirkpatrick, L., Zu, T., Hoogeveen-Westerveld, M., Severijnen, L., Rifé M., Willemsen, R., Nelson, D.L., Oostra, B.A., The generation of a conditional Fmr1 knock out mouse model to study Fmrp function in vivo. Neurobiol Dis. 21:3 (2006 Mar), 549–555 PMID: 16257225.
60. Min, W.W., Yuskaitis, C.J., Yan, Q., Sikorski, C., Chen, S., Jope, R.S., Bauchwitz, R.P., Elevated glycogen synthase kinase-3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential. Neuropharmacology 56:2 (2009 Feb), 463–472, 10.1016/j.neuropharm.2008.09.017 PMID:18952114.
61. Mines, M.A., Yuskaitis, C.J., King, M.K., Beurel, E., Jope, R.S., GSK3 influences social preference and anxiety-related behaviors during social interaction in a mouse model of fragile X syndrome and autism. PLoS One, 5(3), 2010 Mar 16, e9706, 10.1371/journal.pone.0009706 PMID:20300527.
62. Monyak, R.E., Emerson, D., Schoenfeld, B.P., Zheng, X., Chambers, D.B., Rosenfelt, C., Langer, S., Hinchey, P., Choi, C.H., McDonald, T.V., Bolduc, F.V., Sehgal, A., McBride, S.M.J., Jongens, T.A., Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model. Mol. Psychiatr. 22:8 (2017 Aug), 1140–1148, 10.1038/mp.2016.51 PMID:27090306.
63. Nishimura, Y., Martin, C.L., Vazquez-Lopez, A., Spence, S.J., Alvarez-Retuerto, A.I., Sigman, M., Steindler, C., Pellegrini, S., Schanen, N.C., Warren, S.T., Geschwind, D.H., Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways. Hum. Mol. Genet. 16:14 (2007 Jul 15), 1682–1698 PMID: 17519220.
64. Osterweil, E.K., Chuang, S.C., Chubykin, A.A., Sidorov, M., Bianchi, R., Wong, R.K., Bear, M.F., Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome. Neuron 77:2 (2013 Jan 23), 243–250, 10.1016/j.neuron.2012.01.034 PMID:23352161.
65. Pacey, L.K., Heximer, S.P., Hampson, D.R., Increased GABA(B) receptor-mediated signaling reduces the susceptibility of fragile X knockout mice to audiogenic seizures. Mol. Pharmacol. 76:1 (2009 Jul), 18–24, 10.1124/mol.109.056127 PMID:19351745.
66. Paribello, C., Tao, L., Folino, A., Berry-Kravis, E., Tranfaglia, M., Ethell, I.M., Ethell, D.W., Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol., 10, 2010 Oct 11, 91, 10.1186/1471-2377-10-91 PMID:20937127.
67. Pellerin, D., Çaku, A., Fradet, M., Bouvier, P., Dubé J., Corbin, F., Lovastatin corrects ERK pathway hyperactivation in fragile X syndrome: potential of platelet's signaling cascades as new outcome measures in clinical trials. Biomarkers 21:6 (2016 Sep), 497–508, 10.3109/1354750X.2016.1160289 PMID:27058300.
68. Popovich, B.W., Rosenblatt, D.S., Cooper, B.A., Vekemans, M., Intracellular folate distribution in cultured fibroblasts from patients with the fragile X syndrome. Am. J. Hum. Genet. 35:5 (1983 Sep), 869–878 PMID:6614003.
69. Puhl, A.C., Milton, F.A., Cvoro, A., Sieglaff, D.H., Campos, J.C.L., Bernardes, A., Filgueira, C.S., Lindemann, J.L., Deng, T., Neves, F.A.R., Polikarpov, I., Webb, P., Mechanisms of peroxisome proliferator activated receptor γ regulation by non-steroidal anti-inflammatory drugs. Nucl. Recept. Signal., 13, 2015, 10.1621/nrs.13004 e004.
70. Roin, B., Solving the Problem of New Uses. October 1, 2013, 10.2139/ssrn.2337821 Available at Social Science Research Network: https://ssrn.com/abstract=2337821.
71. Rueda, J.R., Ballesteros, J., Tejada, M.I., Systematic review of pharmacological treatments in fragile X syndrome. BMC Neurol., 9, 2009 Oct 13, 53, 10.1186/1471-2377-9-53 Review. PMID:19822023.
72. Rumore, M.M., Medication repurposing in pediatric patients: teaching old drugs new tricks. J. Pediatr. Pharmacol. Therapeut. 21 (2016), 36–53.
73. Sahu, J.K., Gulati, S., Sapra, S., Arya, R., Chauhan, S., Chowdhury, M.R., Gupta, N., Kabra, M., Gupta, Y.K., Dwivedi, S.N., Kalra, V., Effectiveness and safety of donepezil in boys with fragile x syndrome: a double-blind, randomized, controlled pilot study. J. Child Neurol. 28:5 (2013 May), 570–575, 10.1177/0883073812449381 PMID:22752489.
74. Schaefer, T.L., Davenport, M.H., Grainger, L.M., Robinson, C.K., Earnheart, A.T., Stegman, M.S., Lang, A.L., Ashworth, A.A., Molinaro, G., Huber, K.M., Erickson, C.A., Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety. J. Neurodev. Disord., 9(6), 2017 Jun 12, 10.1186/s11689-017-9184-y PMID:28616095.
75. Schneider, A., Leigh, M.J., Adams, P., Nanakul, R., Chechi, T., Olichney, J., Hagerman, R., Hessl, D., Electrocortical changes associated with minocycline treatment in fragile X syndrome. J. Psychopharmacol. 27:10 (2013 Oct), 956–963, 10.1177/0269881113494105 PMID:23981511.
76. Sheppard, K.W., Boone, K.M., Gracious, B., Klebanoff, M.A., Rogers, L.K., Rausch, J., Bartlett, C., Coury, D.L., Keim, S.A., Effect of Omega-3 and -6 supplementation on language in preterm toddlers exhibiting autism spectrum disorder symptoms. J. Autism Dev. Disord. 47 (2017), 3358–3369.
77. Sidorov, M.S., Krueger, D.D., Taylor, M., Gisin, E., Osterweil, E.K., Bear, M.F., Extinction of an instrumental response: a cognitive behavioral assay in Fmr1 knockout mice. Gene Brain Behav. 13:5 (2014 Jun), 451–458, 10.1111/gbb.12137 PMID:24684608.
78. Siller, S.S., Broadie, K., Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase. Dis. Model. Mech. 4:5 (2011 Sep), 673–685, 10.1242/dmm.008045 PMID:21669931.
79. Song, G., Napoli, E., Wong, S., Hagerman, R., Liu, S., Tassone, F., Giulivi, C., Altered redox mitochondrial biology in the neurodegenerative disorder fragile X-tremor/ataxia syndrome: use of antioxidants in precision medicine. Mol. Med., 22, 2016, 10.2119/molmed.2016.00122.
80. Strom, C.M., Brusca, R.M., Pizzi, W.J., Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome. Am. J. Med. Genet. 44:5 (1992 Nov 15), 676–682 PMID:1481832.
81. Sutherland, G.R., The fragile X chromosome. Int. Rev. Cytol. 81 (1983), 107–143 PMID:6347931.
82. Tabolacci, E., De Pascalis, I., Accadia, M., Terracciano, A., Moscato, U., Chiurazzi, P., Neri, G., Modest reactivation of the mutant FMR1 gene by valproic acid is accompanied by histone modifications but not DNA demethylation. Pharmacogenetics Genom. 18:8 (2008 Aug), 738–741, 10.1097/FPC.0b013e32830500a1 PMID:18622267.
83. Teachey, D.T., Greiner, R., Seif, A., Attiyeh, E., Bleesing, J., Choi, J., Manno, C., Rappaport, E., Schwabe, D., Sheen, C., Sullivan, K.E., Zhuang, H., Wechsler, D.S., Grupp, S.A., Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. Br. J. Haematol. 145 (2009), 101–106.
84. Torrioli, M., Vernacotola, S., Setini, C., Bevilacqua, F., Martinelli, D., Snape, M., Hutchison, J.A., Di Raimo, F.R., Tabolacci, E., Neri, G., Treatment with valproic acid ameliorates ADHD symptoms in fragile X syndrome boys. Am. J. Med. Genet. 152A:6 (2010 Jun), 1420–1427, 10.1002/ajmg.a.33484 PMID:20503316.
85. Webb, T., Crawley, P., Bundey, S., Folate treatment of a boy with fragile-X syndrome. J. Ment. Defic. Res. 34:Pt 1 (1990 Feb), 67–73 PMID:2325121.
86. Wells, T.E., Madison, L.S., Assessment of behavior change in a fragile-X syndrome male treated with folic acid. Am. J. Med. Genet. 23:1–2 (1986 Jan-Feb), 291–296 PMID:3953651.
87. Williams, K., Wray, J.A., Wheeler, D.M., Intravenous secretin for autism spectrum disorders (ASD). Cochrane Database Syst. Rev.(4), 2012 Apr 18, CD003495, 10.1002/14651858.CD003495.pub3 Review. PMID:22513913.
88. Wittich, C.M., Burkle, C.M., Lanier, W.L., Ten common questions (and their answers) about off-label drug use. Mayo Clin. Proc. 87 (2012), 982–990.
89. Yuskaitis, C.J., Mines, M.A., King, M.K., Sweatt, J.D., Miller, C.A., Jope, R.S., Lithium ameliorates altered glycogen synthase kinase-3 and behavior in a mouse model of fragile X syndrome. Biochem. Pharmacol. 79:4 (2010 Feb 15), 632–646, 10.1016/j.bcp.2009.09.023 PMID:19799873.
90. Zhang, Y.Q., Bailey, A.M., Matthies, H.J., Renden, R.B., Smith, M.A., Speese, S.D., Rubin, G.M., Broadie, K., Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 107:5 (2001 Nov 30), 591–603 PMID:11733059.