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Antisense oligonucleotide therapeutic approach for Timothy syndrome

Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions1. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A2–6. We reasoned that switching CACNA1C exon utilization from 8A to 8 would represent a potential therapeutic strategy. Here we developed antisense oligonucleotides (ASOs) to effectively decrease the inclusion of exon 8A in human cells both in vitro and, following transplantation, in vivo. We discovered that the ASO-mediated switch from exon 8A to 8 robustly rescued defects in patient-derived cortical organoids and migration in forebrain assembloids. Leveraging a transplantation platform previously developed7, we found that a single intrathecal ASO administration rescued calcium changes and in vivo dendrite retraction of patient neurons, suggesting that suppression of CACNA1C exon 8A expression is a potential treatment for TS1. Broadly, these experiments illustrate how a multilevel, in vivo and in vitro stem cell model-based approach can identify strategies to reverse disease-relevant neural pathophysiology. Antisense oligonucleotides effectively decrease the inclusion of exon 8A of CACNA1C in human cells both in vitro and in rodents transplanted with human brain organoids, and a single intrathecal administration rescued both calcium changes and in vivo dendrite morphology of patient neurons.

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Here's Why Nike (NKE) Fell in Q1 - Insider Monkey

Polen Capital, an investment management company, released its “Polen Focus Growth Strategy” first quarter 2024 investor letter. A copy of the same can be downloaded here.

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IR Spectroscopy Market Size 2024 to 2031.

IR Spectroscopy Market Size 2024 to 2031.
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Atomic Spectroscopy Market Size 2024 to 2031.

Atomic Spectroscopy Market Size 2024 to 2031.
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Spectroscopy Equipment Market Size 2024 to 2031.

Spectroscopy Equipment Market Size 2024 to 2031.
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New TruNarc handheld scanners use Raman light effect from late 1920s to analyze drugs

The Rifle Police Department submitted a letter to Rifle City Council for the Mayor to sign in support of distributing TruNarc scanners to the various regional law enforcement agencies, including Glenwood Springs, Silt, New Castle,...

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Process Spectroscopy Market Shows Booming Growth with

Process Spectroscopy Market Shows Booming Growth with
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WalkMe Introduces Workflow Accelerators to Eliminate Friction in Workflows

WalkMe Introduces Workflow Accelerators to Eliminate Friction in Workflows
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Cell and Gene Therapy Market Is Gaining Huge Growth In Upcoming

Cell and Gene Therapy Market Is Gaining Huge Growth In Upcoming
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Europe Laboratory Information Management System (LIMS)

Dublin, Feb. 16, 2024 (GLOBE NEWSWIRE) -- The

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