A Phase 1/2 Study of Antisense Oligonucleotide Therapy for Treatment of Ataxia-Telangiectasia
Timothy Yu
Summary
This project aims to evaluate the safety and efficacy of precision genetic therapy for patients with Ataxia-telangiectasia (A-T), a rare neurodegenerative disease caused by mutations in the ATM gene. The investigators will conduct a clinical trial to study the safety and efficacy of intrathecal administration of atipeksen, a targeted genetic therapy that restores ATM gene function in A-T individuals bearing the recurrent ATM c.7865C\>T variant. The aim of this study is to delay or forestall progression of neurologic symptoms in A-T and improving quality of life. Success will provide an empirical foundation for advancing additional precision genetic therapies for A-T and other neurodegenerative conditions.
Description
The goal of this protocol is to study the safety and efficacy of the investigational drug atipeksen, a mutation-specific antisense oligonucleotide (ASO), in individuals with ataxia telangiectasia (A-T). The first objective is to evaluate the safety of therapy with atipeksen, a 22-nucleotide oligonucleotide designed to ameliorate the effects of mis-splicing caused by a mutation in the ATM gene(NM\_000051.3), c.7865C\>T (p.Ala2622Val), when administered via intrathecal injection. The second objective is to determine if administration of intrathecal atipeksen can reduce or stabilize neurological…
Eligibility
- Age range
- 0–17 years
- Sex
- All
- Healthy volunteers
- No
INCLUSION/EXCLUSION CRITERIA: Who can take part: * People with classic A-T confirmed by genetic testing * Must have a specific ATM gene change (c.7865C\>T) * Must also have another ATM change that causes A-T Who cannot take part: People with health problems that make lumbar puncture unsafe: * Blood clotting or bleeding problems * Brain conditions raising pressure inside the head * Serious heart or breathing problems * Infection near the lower back Other things doctors will check: * Overall health and stability * Any medicines that might cause problems * Past difficulties with lumbar pun…
Interventions
- DrugAntisense oligonucleotide targeting the ATM gene
Atipeksen is a fully modified PS-2'MOE splice-switching antisense oligonucleotide that is designed to restore normal splicing patterns in patients with the ATM c.7865C\>T mutation.
Location
- Boston Children's HospitalBoston, Massachusetts