Sign in Subscribe
Genetic research

Breakthrough in Gene Therapy: Longitudinal Monitoring of Therapeutic Gene Expression

Strategic Insights

— 1 min read

Researchers at Takeda Pharmaceutical Co. Ltd. have made significant progress in gene therapy by developing a novel positron emission tomography (PET) radiotracer that can monitor therapeutic gene expression in vivo. According to a study published in Molecular Therapy, the new radiotracer, [F]AGAL, has shown promising results in targeting the enzyme deficient in Fabry disease, an inherited genetic disorder.

Key Takeaways:

  • The study utilized Gla knockout mice to evaluate the efficacy of gene therapy using an adeno-associated virus encoding the human GLA (AAV) or recombinant GLA for enzyme replacement studies.
  • The PET imaging studies demonstrated quick renal clearance with high radioactive uptake in the heart at 6 weeks, indicating effective and durable transgene expression from gene therapy.
  • The study also showed good concordance between in vivo PET imaging and ex vivo quantification of GLA levels in biofluids and tissues.
  • The biodistribution and dosimetry in non-human primates showed acceptable radiation exposure for multiple injections, demonstrating the potential for translation to clinical trial use.
  • The novel PET tracer [F]AGAL exhibited pH-dependent binding to GLA, suggesting recognition of the active enzyme residing within the acidified lysosomes.
  • The study utilized a novel PET imaging platform to guide treatment response and dose optimization in gene therapy.

Statistics:

  • 6 weeks: Time required for renal clearance and high radioactive uptake in the heart.
  • 26 weeks: Duration of sustained transgene expression from gene therapy.
  • 50 Hampshire St, Floor 5, Cambridge, MA 02139, USA: Address of Cell Press, the publisher of Molecular Therapy.
  • 2024: Year of publication for the study on Longitudinal imaging of therapeutic enzyme expression after gene therapy for Fabry disease using positron emission tomography.

Sources:

  • Longitudinal imaging of therapeutic enzyme expression after gene therapy for Fabry disease using positron emission tomography and the radiotracer [18F]AGAL. Molecular Therapy, 2024;33(9):4381-4393.
  • Takeda Pharmaceutical Co. Ltd.: A Japanese multinational pharmaceutical company.
  • Molecular Therapy: A peer-reviewed journal published by Cell Press.

Read more