The Development of an Antisense Oligonucleotide Therapy for Angelman Syndrome

Quick Overview

Dr. Frank Bennett, Senior Vice President of Research at Ionis Pharmaceuticals, presented at the 2019 FAST Science Summit on the development of an antisense oligonucleotide therapy for Angelman syndrome. The therapy aims to reactivate the paternal copy of the UBE3A gene, which is silenced in individuals with Angelman syndrome. Through the use of antisense drugs, the UBE3A antisense transcript can be downregulated, allowing for the production of UBE3A protein. The therapy has shown promising results in cell culture and animal models, and a clinical trial is expected to start in the second half of next year. Dr. Bennett emphasized the importance of participating in natural history studies and consulting with physicians to determine the best clinical trial for each individual.

Introduction

In this talk, we will discuss the development of an antisense oligonucleotide therapy for Angelman syndrome. The therapy is being developed by Ionis Pharmaceuticals in collaboration with Biogen. Dr. Frank Bennett, Senior Vice President of Research at Ionis Pharmaceuticals, will provide insights into the progress made in this field.

Background

Angelman syndrome is a neurologic disorder characterized by the silencing of the paternal copy of the UBE3A gene. This gene is responsible for producing the UBE3A protein, which is essential for normal brain function. The goal of the therapy is to reactivate the silenced paternal copy of the gene and restore UBE3A protein production.

Antisense Oligonucleotide Technology

Ionis Pharmaceuticals has pioneered the development of antisense technology, which involves designing small snippets of nucleic acids (DNA or RNA) that can bind to specific RNA molecules. By binding to the target RNA, the antisense drug can induce various effects, such as degradation of the RNA or increasing its production. In the case of Angelman syndrome, the antisense drug is designed to degrade the UBE3A antisense transcript, leading to an increase in UBE3A RNA and protein production.

Progress and Clinical Trials

Ionis Pharmaceuticals has conducted extensive screenings to identify an antisense drug candidate for Angelman syndrome. The drug has been tested in cell culture assays and animal models, demonstrating its ability to decrease the UBE3A antisense transcript and increase UBE3A protein production. The company has also created transgenic mice that express the human UBE3A gene, allowing them to test the drug’s effectiveness in engaging the human gene.

The next steps for the program include completing safety studies, discussing the program with regulatory agencies, and collaborating with physicians and key opinion leaders to design the clinical trial. Ionis Pharmaceuticals aims to start the clinical trial in the second half of next year.

Considerations for Clinical Trials

It is important to note that multiple clinical trials for Angelman syndrome will be starting in the next 12 to 18 months, each with its own unique set of properties. Patients and their families should carefully consider the pros and cons of each drug and consult with their physicians to determine the most suitable study to participate in. Natural history studies are also recommended to gain a better understanding of the disease and the commitment required for participating in clinical trials.

Conclusion

The development of an antisense oligonucleotide therapy for Angelman syndrome is an exciting advancement in the field. Ionis Pharmaceuticals, in collaboration with Biogen, is committed to bringing a drug forward for the treatment of Angelman syndrome. Extensive screenings and research have led to the identification of a drug candidate, and the company is working towards starting a clinical trial in the near future. The support and participation of the Angelman community have been instrumental in the progress made so far.