TS1-ASO for Timothy Syndrome

(TS1-ASO Trial)

Overseen By Grant Wells

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Stanford University

Disqualifiers: Critical illness, Secondary genetic disorder, Hypoxic-ischemic injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new treatment, TS1-ASO, can safely assist children with Timothy Syndrome Type 1 (TS1) by addressing symptoms related to brain development and function. The study will evaluate the treatment's safety and efficacy when administered through a lumbar puncture, a procedure that injects medicine into the spinal fluid. Eligible children must have TS1 confirmed by a specific genetic test and show early signs of developmental or neurological issues. Participants will undergo regular check-ups, including brain and heart monitoring, and provide samples for analysis. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering participants the chance to be among the first to potentially benefit from this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that TS1-ASO is likely to be safe for humans?

Research has shown that TS1-ASO, a type of genetic therapy, is under study for its safety in treating Timothy Syndrome. Early studies found that this treatment did not cause major harm or trigger adverse immune reactions, suggesting it might be well-tolerated by the body.

Although TS1-ASO is not yet approved for any condition, early trials in lab settings, such as those with rats, have shown promise. These studies indicated that the treatment effectively targeted the disease without causing significant side effects. The current trial is in its early stages, focusing mainly on ensuring its safety for humans.

Participants in the trial will receive the treatment through a spinal injection to assess human tolerance. Researchers will closely monitor for any side effects to ensure participant safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Timothy Syndrome?

Unlike other treatments for Timothy Syndrome, which often focus on managing symptoms with beta-blockers or calcium channel blockers, TS1-ASO offers a novel approach by directly targeting the genetic cause of the condition. Researchers are excited because TS1-ASO is an antisense oligonucleotide, a type of genetic therapy designed to modify the expression of the gene responsible for Timothy Syndrome. This targeted mechanism is expected to address the root cause rather than just alleviate symptoms, potentially leading to more effective and long-lasting outcomes.

What evidence suggests that TS1-ASO might be an effective treatment for Timothy Syndrome?

Research has shown that TS1-ASO, a type of genetic treatment, may help treat Timothy Syndrome. Studies have found that this treatment can decrease the presence of a specific gene segment linked to the condition in human cells. In lab tests, injecting this treatment into rats with human-like Timothy Syndrome led to noticeable improvements in cell function. Early results suggest that this therapy might help restore normal cell growth and function. Although more research is needed, these findings highlight the potential of TS1-ASO in addressing the developmental challenges of Timothy Syndrome. Participants in this trial will receive TS1-ASO to further evaluate its effectiveness and safety. ^{1 2 3 4 6}

Who Is on the Research Team?

Sergiu Pasca, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for children older than 2 months who have Timothy Syndrome Type 1 confirmed by genetic testing. It aims to include those early in life, before or as neurodevelopmental symptoms begin.

Inclusion Criteria

I have the CACNA1C gene variant c.1216 G>A, p.G406R in exon 8A.

I am older than 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intrathecal injections of TS1-ASO via lumbar puncture using a stepwise dose-escalation approach

12 months

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neurologic exams, cardiac monitoring, and laboratory testing

12 months

Regular follow-up visits

Long-term follow-up

Longitudinal follow-up allows for assessment of durability of response and continued safety evaluation over time

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

• TS1-ASO

Trial Overview

Researchers are testing TS1-ASO, a new medicine given through spinal injections, to see if it is safe and can help prevent or treat brain and behavior problems in kids with Timothy Syndrome. All participants receive the treatment; there is no comparison group.

How Is the Trial Designed?

Group I: TS1-ASO Arm Experimental Treatment 1 Intervention

TS1-ASO Drug Administration

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Citations

1.

nature.com

nature.com/articles/s41586-024-07310-6

Antisense oligonucleotide therapeutic approach for ...

We discovered that intrathecal injection of an ASO into rats transplanted with human TS1 cortical organoids resulted in a robust downregulation ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07600658

A Phase I/II, First-In-Human Trial to Evaluate the Safety, ...

The goal of this clinical trial is to learn if an antisense oligonucleotide (TS1-ASO) can safely treat and potentially prevent ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38658687/

Antisense oligonucleotide therapeutic approach for Timothy ...

Here we developed antisense oligonucleotides (ASOs) to effectively decrease the inclusion of exon 8A in human cells both in vitro and, following ...

4.

techfinder.stanford.edu

techfinder.stanford.edu/technology/treatment-timothy-syndrome-using-antisense-oligonucleotide

Treatment of Timothy syndrome using an antisense ... - Stanford

This ASO therefore has significant promise for the treatment of Timothy syndrome. Stage of Development In vitro: selectively causes mutagenic exon 8A ...

5.

withpower.com

withpower.com/trial/phase-2-timothy-syndrome-8-2026-b6af4

TS1-ASO for Timothy Syndrome · Info for Participants

The goal of this clinical trial is to learn if an antisense oligonucleotide (TS1-ASO) can safely treat and potentially prevent ...

6.

cirm.ca.gov

cirm.ca.gov/wp-content/uploads/2024/05/Letters-to-the-Board11-TRAN1-16236.pdf

Stanford University

We propose to perform the necessary preclinical studies to create a first-in-class antisense oligonucleotide (ASO) to treat Timothy syndrome (TS), a disorder ...