Understanding Gene Therapy in Duchenne

Gene therapy has made significant strides in Duchenne muscular dystrophy, with one therapy approved and other potential therapies in various stages of development.

As our community continues to see progress, many new concepts and terms arise, ones that families have not had to consider before.

PPMD’s resources aim to empower and inform families like yours, providing insights and guidance to help you better understand the dynamic landscape of gene therapy.

We’re here to support you on this journey, offering clarity and knowledge as we navigate this evolving field together.

Approved Duchenne Gene Therapies

ELEVIDYS is an adeno-associated virus (AAV) vector-based micro-dystropin gene therapy indicated for the treatment of people with Duchenne muscular dystrophy who are at least 4 years of age and do not have antibodies to AAVrh74.

  • The indication in ambulatory patients is approved under traditional approval based on functional benefits observed in patients treated with ELEVIDYS.
  • The indication in non-ambulatory patients is under the accelerated approval pathway based on increased levels in micro-dystrophin being reasonably likely to predict clinical benefit in the non-ambulatory population and will require confirmatory studies to convert to traditional approval.

View PPMD’s resources regarding eligibility and access to ELEVIDYS >

Gene Therapy 101

This 3-minute video provides an overview of the basics of gene therapy in Duchenne.

What is gene therapy?

  • Duchenne is a genetic disorder caused by a variant in the gene that codes for the protein dystrophin. Dystrophin is important for proper muscle function.
  • In Duchenne, the dystrophin gene is dysfunctional and produces little to no dystrophin. This causes muscle cells to become easily damaged leading to loss of muscle.
  • Gene therapy is being developed as a therapy option to treat Duchenne. The goal of gene therapy is to introduce DNA instructions (or transgenes) to cells in the body to treat a disease.

What are the different types?

There are different types of gene therapy, but they all have the same goal – to change the disease progression. This can be done by:

  • Replacing the dysfunctional gene with a functional copy
  • Correcting the disease-causing variant in the gene
  • Introducing a new or modified gene that can help treat the disease
What are the components?

Gene therapy has three important components:

  • The transgene, which is the genetic material being delivered.
  • The vector which carries the transgene into cells. Vectors are usually inactive viruses that will not cause an infection.
  • The promoter which turns the transgene on in specific tissue(s). For example, a functioning copy of the dystrophin gene may be carried by an adeno-associated virus (AAV) and turned on by muscle and/or heart-specific promoters.

What are the limitations?

Like all therapies, gene therapy has limitations, which can include:

  • While gene therapy can be used to slow down disease progression or potentially improve function, it isn’t a cure.
  • How long the benefits last could vary from person to person and depending on the type of gene therapy used.
  • The treatment’s effectiveness may depend on the person’s age and disease stage.
  • Not everyone is eligible to receive gene therapy because it wouldn’t be safe or effective for them. For example, someone who has pre-existing antibodies against the vector cannot receive gene therapy because those antibodies could limit the effectiveness of the therapy and pose safety risks from an immune response.
  • Patients cannot be re-dosed because their body will produce a significant number of antibodies after the initial delivery, so gene therapy is currently a one-time treatment.
  • It is possible that a serious immune response could lead to organ failure or death.

What is the future of gene therapy?

Researchers are working hard to make gene therapy more safe and effective, including exploring:

  • Different vectors
  • Strategies to suppress the immune response

By limiting the immune response, people with pre-existing antibodies or antibodies developed as a result of a previous gene therapy may be able to receive gene therapy in the future.

Video Series 1: Understanding AAV in Gene Therapy

Researchers in Duchenne are currently using an adeno-associated virus (AAV) to deliver the genetic code for dystrophin or other proteins into muscle cells in the body. Learn about the properties of AAV and why it is used, the immune challenges, as well as potential safety concerns.

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Video Series 2: Gene Replacement with Micro-Dystrophin

There are numerous gene therapy strategies in development for Duchenne. Gene replacement strategies with a micro-dystrophin transgene are the furthest along in development and testing and is likely to be an option for a large percentage of people with Duchenne.

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Gene Therapy Trials & Results Data

The tools and resources below provide an overview of what data is available on the gene therapies so far, as well as the currently enrolling clinical trials. It is important to note that this is a rapidly changing area of research, and it is possible that very recent changes or data may not yet be included.

Explore:

Currently Enrolling Trials

This table includes more information about the clinical trials for gene therapies, including the trials that are currently enrolling or expected to begin enrollment.

Current Gene Therapies & Results Data

The table below describes the current gene therapies and gives information so that families can see what they have in common and how they are different. This table also includes very short summaries of results data that have been released thus far, as well as information about side effects.

Our Understanding of Current Data

Many families ask us which of these gene therapies is the “best”, and the answer to that is that we do not yet know. Because the gene therapies are in clinical trials, we are still gathering data to understand how well they work and how long they last.

  • The data that we currently have suggests that the gene therapies, especially at the current higher doses, result in increased expression of the micro/mini-dystrophin and that the increase lasts for at least a year.
  • Current data also shows that most boys who receive the gene therapy will have side effects. For most, the side effects occur soon after the dosing and are manageable with medications such as steroids and other treatment, and in some cases, hospitalizations.
  • We also know that, tragically, one child died after receiving gene therapy. Details regarding what happened for that child are limited.
  • We also do not yet know how well the micro/mini-dystrophins will function as a replacement for standard dystrophin or how long the production of the micro/mini-dystrophin will last.

Additional Gene Therapy Topics

Dive deeper into in-depth gene therapy topics.

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Gene Therapy Terms to Know

Below are some of the essential terms related to gene therapy and Duchenne.

AAV

Adeno–associated viruses (AAV) are small viruses that can be deactivated and used to transmit gene–based treatments to patients.

Antibody

A protein used by the immune system to recognize foreign material in the body. An antibody can bind foreign material to prevent it from infecting a cell or signal the immune system to attach an infected cell.

Antibody Titer

The measure of how many antibodies a person has for a particular virus. An individual can be tested for the amount of antibodies in the blood that prevent AAV from infecting a cell, i.e. neutralizing antibodies. Alternatively, an individual can be tested for the presence of antibodies that can bind to AAV, though the ability of an antibody to bind a virus does not mean it will prevent the virus from infecting a cell.

Capsid

The outside shell that protects a virus and helps it penetrate a cell membrane. A capsid is a protein coat that surrounds a virus. A capsid protects the contents, and helps the virus attach to a targeted cell to penetrate the cell membrane. In gene editing, the special characteristics of a capsid can enable gene delivery to specific cells.

CRISPR

CRISPR is a gene–editing technique that allows scientists to alter DNA sequences easily and precisely in order to modify gene function. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats that are a type of DNA sequence in a gene. This type of DNA sequence is understood by scientists who can use molecular tools to modify how the gene functions.

Gene Editing

Gene editing makes targeted changes to existing DNA in genes located on the chromosomes. With gene editing, researchers can enable or disable targeted genes, correct harmful mutations, and change the activity of specific genes. Gene editing is a set of techniques that enable researchers and clinicians to rewrite the instruction encoded in the DNA of genes. These molecular–biology techniques can enable or disable targeted genes, correct harmful mutations, modify expression of genes or change activity of a specific cell, with the goal of restoring normal function. CRISPR is an example of a gene editing technique.

Gene Therapy

Gene therapy is a technique that modifies a person’s genes to treat or cure disease. Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use. Gene therapies can work by several mechanisms:

  • Replacing a disease–causing gene with a healthy copy of the gene
  • Inactivating a disease–causing gene that is not functioning properly
  • Introducing a new or modified gene into the body to help treat a disease

Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.

Genes

Regions of DNA that direct the production of proteins that are the building blocks of our bodies. Genes are inherited from our biological parents. Defective genes can result in a disease or medical disorder. Genes direct biologically important functions throughout the body. Mutations, or errors, in genes can cause disease by failing to produce sufficient levels of a functional protein.

Neutralizing Antibodies

A type of antibody that binds foreign material, like a virus, and prevents it from infecting cells.

Pre-existing Antibodies

Antibodies to a specific virus that an individual has been exposed to and the immune system has developed antibodies to prevent future infection.

Promoter

A sequence of DNA that controls where in the body the transgene is expressed or turned on.

Serotypes

Different variations of viruses. Adeno-associated virus has many serotypes being tested in clinical trials. Serotypes can be naturally occurring variations or modified versions created by researchers. Antibodies to one serotype may still retain the ability to neutralize another variant.

Transgene

The genetic material being delivered to modify, replace, or restore gene expression to begin producing protein.

Tropism

The ability of different vectors to target specific cell types or tissues. A tropism is the natural attraction of a virus or vector to receptors present only on certain cells or tissues. Gene therapy researchers exploit tropisms to help different viruses, lipid particles, or other therapeutic carriers reach their targeted cells.

Vector

Modified virus, cells, or nanoparticles that shuttle the transgene and promoter DNA sequences into the cells of the body.