Therapeutic Development and Outcome Evaluation using a Disease Concept Model in Angelman Syndrome

Quick Overview

Dr. Meghan Miller from Roche presented at the 2017 FAST Science Summit about the therapeutic development and outcome evaluation using a disease concept model in Angelman Syndrome (AS). Roche is focused on finding disease-modifying therapeutic approaches for rare diseases like AS, with the goal of making a transformative impact on the lives of patients and caregivers. They are developing a targeted therapeutic approach using an LNA antisense oligonucleotide to replace the loss of the UBE3A protein in AS patients. Roche is also working on identifying biomarkers and outcome measures, such as molecular markers in the cerebrospinal fluid (CSF) and EEG analysis, to assess the efficacy of their therapeutic approach. They are collaborating with the AS community to develop meaningful outcome measures and are planning an endpoint-enabling study in patients. The disease concept model is being used to identify relevant outcome measures for AS. Roche’s efforts in therapeutic development and outcome evaluation offer hope for the AS community.

Introduction

Dr. Meghan Miller, project leader in discovery for neurodevelopmental and neuromuscular disorders at Roche, joins the Angelman community to discuss Roche’s efforts in developing biomarkers and outcome measures in a disease concept model. She highlights the importance of finding disease-modifying therapeutic approaches for rare diseases and the need for transformative therapies in the lives of patients and caregivers.

Targeting a Transformative Therapy for Angelman Syndrome

Dr. Miller explains that Roche is focused on developing a targeted therapeutic approach for Angelman Syndrome. The underlying cause of the disease is the loss of function of the UBE3A gene, specifically the loss of the maternal UBE3A protein. Roche’s approach involves using an LNA antisense oligonucleotide to recognize and degrade the long non-coding RNA that is silencing the paternal UBE3A gene, allowing for the re-expression of the paternal UBE3A copy.

Biomarkers and Outcome Measures

Roche is working on developing biomarkers and outcome measures to assess the effectiveness of their therapeutic approach. Dr. Miller discusses the importance of human biomarkers, particularly in the cerebrospinal fluid (CSF), to understand the distribution and molecular effect of the therapeutic molecule. She also highlights the use of EEG to measure brain activity and the potential for digital devices to provide continuous and less invasive monitoring in the home setting.

Disease Concept Model

Dr. Miller introduces the disease concept model, a collaborative effort between Roche, the ABOM consortia, and the Angelman community. This model aims to identify relevant outcome measures for Angelman Syndrome through a qualitative assessment of caregivers and clinicians, followed by a quantitative global assessment. The goal is to understand the burden of the disease and identify the best clinical assessments to measure its characteristics.

Conclusion

Dr. Miller expresses her gratitude for the efforts of the Angelman community in participating in trials, interviews, and other research activities. She emphasizes the importance of these efforts in advancing therapeutic development and outcome evaluation for Angelman Syndrome.