Rare Diseases Report 2022

Rett syndrome: Looking to the future and the promise of gene therapy


 

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35. Acadia Pharmaceuticals Inc. Study of trofinetide for the treatment of girls and women with Rett syndrome (LAVENDER™). ClinicalTrials.gov identifier: NCT04181723. Updated Feb 17, 2022. Accessed Feb 23, 2022. https://clinicaltrials.gov/ct2/show/NCT04181723.

36. Acadia Pharmaceuticals announces positive top-line results from the pivotal phase 3 LAVENDER trial of trofinetide in Rett syndrome. Press release. Acadia Pharmaceuticals Inc. Dec 6, 2021. Accessed Feb 23, 2022. https://ir.acadia-pharm.com/news-releases/news-release-details/acadia-pharmaceuticals-announces-positive-top-line-results-1.

37. Copping NA et al. Emerging gene and small molecule therapies for the neurodevelopmental disorder Angelman syndrome. Neurotherapeutics. 2021 Jul;18(3):1535-47. doi: 10.1007/s13311-021-01082-x.

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39. Glaze DG et al; Rett 002 Study Group. Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome. Neurology. 2019 April 16;92(16):e1912-e1925. doi: 10.1212/WNL.0000000000007316.

40. Acadia Pharmaceuticals Inc. An open-label study of trofinetide for the treatment of girls two to five years of age who have Rett syndrome (DAFFODIL™). ClinicalTrials.gov Identifier: NCT04988867. Updated Jan 24, 2022. Accessed Feb 23, 2022. https://clinicaltrials.gov/ct2/show/NCT04988867.

41. Anavex Life Sciences announces ANAVEX®2-73 meets primary and secondary endpoints in clinical trial. Press release. Anavex Life Sciences Corp. Dec 15, 2020. Accessed Feb 23, 2022. http://www.anavex.com/post/anavex-life-sciences-announces-anavex-2-73-meets-primary-and-secondary-endpoints-in-clinical-trial.

42. Anavex Life Sciences Corp. ANAVEX2-73 study in patients with Rett syndrome (AVATAR). ClinicalTrials.gov Identifier: NCT03941444. Updated Jan 27, 2022. Accessed Feb 23, 2022. https://clinicaltrials.gov/ct2/show/NCT03941444.

43. Anavex Life Sciences Corp. ANAVEX2-73 study in pediatric patients with Rett syndrome (EXCELLENCE). ClinicalTrials.gov Identifier: NCT04304482. Updated Sep 28, 2021. Accessed Feb 23, 2022. http://www.clinicaltrials.gov/ct2/show/NCT04304482.

44.Christ MG et al. The Sigma-1 receptor at the crossroad of proteostasis, neurodegeneration, and autophagy. Trends Neurosci. 2020 Feb;43(2):79-81. doi: 10.1016/j.tins.2019.12.002.

45. Kaufmann WE et al. ANAVEX®2-73 (blarcamesine), a sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome. Pharmacol Biochem Behav. 2019 Dec;187:172796. doi: 10.1016/j.pbb.2019.172796.

46. Brimson JM et al. Dipentylammonium binds to the sigma-1 receptor and protects against glutamate toxicity, attenuates dopamine toxicity and potentiates neurite outgrowth in various cultured cell lines. Neurotox Res. 2018 Aug;34(2):263-72. doi: 10.1007/s12640-018-9883-5.

47. Kourrich S et al. The sigma-1 receptor: roles in neuronal plasticity and disease. Trends Neurosci. 2012 Dec;35(12):762-71. doi: 10.1016/j.tins.2012.09.007.

48. Lappalainen R, Riikonen RS. High levels of cerebrospinal fluid glutamate in Rett syndrome. Pediatr Neurol. 1996 Oct;15(3):213-6. doi: 10.1016/s0887-8994(96)00218-4.

49. Hamberger A et al. Elevated CSF glutamate in Rett syndrome. Neuropediatrics. 1992;23(4):212-3. doi: 10.1055/s-2008-1071344.

50. Inacio P. FDA acts to support development of potential gene therapy, TSHA-102. Rett Syndrome News [Internet]. Oct 16, 2020. Accessed Feb 23, 2022. https://rettsyndromenews.com/2020/10/16/fda-grants-orphan-drug-rare-pediatric-disease-status-to-tsha-102-potential-rett-gene-therapy.

51. Sinnett SE et al. Engineered microRNA-based regulatory element permits safe high-dose miniMECP2 gene therapy in Rett mice. Brain. 2021 Nov 29;144(10):3005-19. doi: 10.1093/brain/awab182.

52. Le TTH et al. Efficient and precise CRISPR/Cas9-mediated MECP2 modifications in human-induced pluripotent stem cells. Front Genet. 2019 Jul 2;10:625. doi: 10.3389/fgene.2019.00625.

53. Koerner MV et al. Toxicity of overexpressed MeCP2 is independent of HDAC3 activity. Genes Dev. 2018;32(23-24):1514-24. doi: 10.1101/gad.320325.118.

54. Heckman LD et al. Rett-causing mutations reveal two domains critical for MeCP2 function and for toxicity in MECP2 duplication syndrome mice. Elife. 2014;3:e02676. doi: 10.7554/eLife.02676.

55. Neurogene announces new development program in Rett syndrome utilizing novel EXACT technology platform [Internet]. Accessed Aug 12, 2022. https://www.neurogene.com/press-releases/neurogene-announces-new-development-program-in-rett-syndrome-utilizing-novel-exact-technology-platform/

56. Anzalone AV et al. Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors. Nat Biotechnol. 2020 Jul;38(7):824-44. doi: 10.1038/s41587-020-0561-9.

57. Gaudelli NM, Komor AC, Rees HA, et al. Programmable base editing of AT to GC in genomic DNA without DNA cleavage. Nature. 2017 Nov 23;551(7681):464-71. doi: 10.1038/nature24644.

58. Coenraads M. How RSRT is driving the search for a Rett cure. Rett Syndrome Research Trust [Internet]. Dec 7, 2021. Accessed Feb 23, 2022. https://rettnews.org/articles/how-rsrt-is-driving-the-search-for-a-rett-cure.

59. Cutting-edge technologies to repair the underlying mutations that cause Rett. Rett Syndrome Research Trust [Internet]. Updated Nov 3, 2021. Accessed Feb 23, 2022. https://reverserett.org/research/cures/gene-editing.

60. Sinnamon JR et al. In vivo repair of a protein underlying a neurological disorder by programmable RNA editing. Cell Rep. 2020 Jul 14;32(2):107878. doi: 10.1016/j.celrep.2020.107878.

61. Sinnamon JR et al. Site-directed RNA repair of endogenous Mecp2 RNA in neurons. Proc Natl Acad Sci U S A. 2017 Oct 31;114(44):E9395-E9402. doi: 10.1073/pnas.1715320114.

62. Pipeline. VICO Therapeutics [Internet]. Updated Nov 5, 2021. Accessed Feb 23, 2022. https://vicotx.com/pipeline.

63. Therapeutics platform. Shape Therapeutics [Internet]. Updated Feb 20, 2021. Accessed Feb 23, 2022.

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64. Koeberl DD et al. Glycogen storage disease types I and II: Treatment updates. J Inherit Metab Dis. 2007 Apr;30(2):159-64. doi: 10.1007/s10545-007-0519-9.

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