PTC Therapeutics – Gene Therapy for Angelman Syndrome

Quick Overview

Dr. Edwin Weeber and Dr. Jodi Cook from PTC Therapeutics presented an update on their gene therapy program for Angelman syndrome at the 2018 FAST Science Summit. They discussed their use of adeno-associated virus (AAV) to replace the UBE3A gene and the positive results they have seen in mouse and rat models. They also highlighted the importance of biomarkers in determining the efficacy of gene replacement therapy and addressed concerns about overexpression. The researchers expressed optimism about the progress being made in the field and the potential for future clinical trials.

Introduction

At the 2018 FAST Science Summit, Dr. Edwin Weeber and Dr. Jodi Cook from PTC Therapeutics presented an update on their gene therapy program for Angelman Syndrome. PTC Therapeutics is a global rare disease company that focuses on developing therapies for rare diseases. They have recently acquired Agilis, a company with expertise in gene therapy, and are now working on advancing their gene therapy program for Angelman Syndrome.

The Promise of Gene Therapy

Gene therapy involves replacing or correcting faulty genes to treat genetic disorders. In the case of Angelman Syndrome, the goal is to replace the UBE3A gene, which is responsible for the syndrome. PTC Therapeutics has been working on this approach for several years and has made significant progress in developing a gene therapy treatment for Angelman Syndrome.

The Journey So Far

Dr. Weeber explained that their initial experiments involved using adeno-associated virus (AAV) to deliver the UBE3A gene to the brain. They found that this approach resulted in increased UBE3A protein levels in the brain, leading to improvements in learning and memory in mouse models of Angelman Syndrome.

Advancements in Distribution

To improve the distribution of the gene therapy treatment, PTC Therapeutics has been exploring different routes of administration. They have found that injecting the AAV into the lateral ventricles of the brain allows for better distribution of the UBE3A protein throughout the brain. This approach has shown promising results in both mouse and rat models of Angelman Syndrome.

Biomarkers and Overexpression

One of the challenges in gene therapy is determining whether the treatment is effectively delivering the desired protein. PTC Therapeutics has been working on identifying biomarkers that can indicate the presence of the UBE3A protein in the brain. They have successfully identified a biomarker in cerebrospinal fluid (CSF) that correlates with UBE3A protein levels. This non-invasive method allows for monitoring the effectiveness of the gene therapy treatment.

Additionally, PTC Therapeutics has been studying the potential for overexpression of the UBE3A gene. While overexpression has been associated with autism-like traits in some cases, the results from PTC Therapeutics’ studies have shown that moderate overexpression of UBE3A does not have any deleterious effects on behavior in animal models.

Moving Forward

PTC Therapeutics is actively working towards advancing their gene therapy program for Angelman Syndrome. They are collaborating with the University of South Florida and other partners to further develop and refine their treatment approach. They are also preparing for future clinical trials and are committed to ensuring the safety and efficacy of their gene therapy treatment.

Conclusion

The progress made by PTC Therapeutics in developing a gene therapy treatment for Angelman Syndrome is promising. With advancements in distribution, the identification of biomarkers, and a better understanding of overexpression, PTC Therapeutics is moving closer to clinical trials. The company remains committed to bringing effective therapies to children with Angelman Syndrome and is optimistic about the future of gene therapy for this rare genetic disorder.