Angelman Syndrome Genetics 101 and 102

Quick Overview

This presentation provides an overview of the genetics of Angelman Syndrome and discusses potential therapeutics. The speaker explains the basics of genetics, including DNA, genes, and chromosomes, and how changes in the UBE3A gene can lead to Angelman Syndrome. Different types of genetic changes, such as deletions and mutations, are discussed, as well as the role of imprinting in the condition. The speaker also highlights the importance of outcome measures in clinical trials and encourages participation in research. The presentation concludes with a reminder to prioritize health, seek support from the community, and stay informed about ongoing research.

Introduction

Welcome to the 2021 ASF Virtual Family Conference! In this session, we will be discussing the genetics of Angelman Syndrome. This session is divided into two parts: Genetics 101 and Genetics 102. We will cover the basics of genetics, the research being conducted, and the potential for better therapeutics. Let’s get started!

Genetics 101: Understanding the Basics

DNA and Genes

DNA, or deoxyribonucleic acid, contains all the instructions for life. It is found in the nucleus of cells and is organized into structures called chromosomes. Genes are specific segments of DNA that contain information for making proteins. Proteins are essential for various functions in the body, such as signaling, structure, and machinery.

Chromosomes and Angelman Syndrome

Angelman Syndrome is caused by a loss of function of the UBE3A protein in the brain. UBE3A is encoded by a gene located on chromosome 15. In most cells of the body, both copies of chromosome 15 are active. However, in neurons, the copy inherited from the mother is active, while the copy inherited from the father is silenced. This is due to a process called imprinting, where the cell recognizes and distinguishes between the maternal and paternal chromosomes.

Types of Angelman Syndrome

Angelman Syndrome can be caused by different genetic mechanisms. The most common mechanism is a deletion, where a portion of chromosome 15 is missing. Other mechanisms include mutations in the UBE3A gene, uniparental disomy (inheriting two copies of the chromosome from one parent), and imprinting defects. The severity of Angelman Syndrome can vary depending on the specific genetic mechanism.

Genetics 102: Therapeutics and Clinical Trials

Therapeutic Strategies

There are two main strategies being explored for the treatment of Angelman Syndrome. The first is to replace or activate the silenced UBE3A gene in neurons. This can be done by turning on the paternal copy or introducing a new copy of UBE3A using viral vectors. The second strategy is to develop drugs or compounds that can compensate for the loss of UBE3A function in neurons.

Clinical Trials and Outcome Measures

Clinical trials are essential for testing the safety and efficacy of potential therapeutics. Outcome measures are used to assess the effectiveness of a treatment. In Angelman Syndrome, finding appropriate outcome measures can be challenging due to the variability of symptoms and the small size of the patient population. It is crucial for individuals and families to participate in clinical trials and contribute to the data collection process.

Importance of Trial Design and Community Support

Placebo-controlled trials are necessary to determine the true effects of a treatment. The placebo effect and the nocebo effect (negative response to a placebo) can influence trial outcomes. It is important for the community to support and participate in trials while following the guidelines and protocols set by the researchers and medical professionals.

Looking Ahead

The field of Angelman Syndrome research is rapidly advancing, and there is hope for the development of effective therapeutics. It is important for individuals and families to stay informed, participate in trials, and support ongoing research efforts. Together, we can make a difference in the lives of individuals with Angelman Syndrome.