Multiple Sulfatase Deficiency (MSD) Gene Therapy Trial

What does this milestone mean?

FDA clearance of the IND application is an important step. It means the first-in-human clinical trial for AAV9/SUMF1 can move forward to the next stage of preparation. However, the clinical trial is not starting immediately, and several steps still need to be completed before participants can be enrolled.

Over the next several months, the study team will continue preparing for the clinical trial. This includes finalizing the clinical trial protocol and completing the processes needed to safely conduct the study and collect data in a way that meets FDA requirements. The principal investigators of the MSD Gene Therapy Trial, Dr. Laura Adang and Dr. Rebecca Ahrens-Nicklas, discussed some of the activities that happen after an IND application is approved with Dr. Joni Rutter (NCATS) and Dr. Tania Kampaus (Foundation for the National Institutes of Health) as part of the BGTC educational video series. View their discussion here.

We understand that families have questions about when the clinical trial will begin and how they can express interest in participation. As explained in the letter below, those details have not yet been finalized. NCATS, as the IND sponsor, and the study’s principal investigators will share more information with the MSD community as it becomes available.

What is gene therapy?

Gene therapy is an approach to treating or preventing disease by changing how genes work in the body. Genes contain instructions that tell our cells how to make proteins needed for normal health. When a gene is missing, not working correctly, or produces a harmful protein, it can lead to disease.

Depending on the condition, gene therapy may:

• Add a working copy of a gene 
• Replace or repair a faulty gene 
• Turn a gene on or off 
• Help cells make a beneficial protein 

Some gene therapies are designed to treat the underlying cause of a disease rather than just its symptoms. Others may help slow disease progression or improve how the body functions. While some gene therapies have been approved to treat certain diseases, many others are still being studied in clinical trials. Researchers are continuing to monitor these therapies to better understand their long-term safety and effectiveness.

What are the different types of AAV vectors?

Adeno-associated viruses (AAVs) are commonly used as "delivery vehicles," or vectors, in gene therapy. Scientists modify these viruses so they cannot cause disease but can carry genetic instructions into cells to help treat a disease or condition.

There are several naturally occurring AAV types, called serotypes, including AAV1, AAV2, AAV5, AAV8, AAV9, and others. Each serotype has unique properties that influence which tissues or organs it is most likely to reach after treatment. 

For example:

• AAV1 has been studied for targeting muscle tissue. 
• AAV2 has been studied for eye diseases. 
• AAV5 has been studied for liver and nervous system disorders. 
• AAV8 has been studied for targeting the liver. 
• AAV9 has been studied for targeting the nervous system, heart, and skeletal muscle, particularly for neurological and neuromuscular disorders.

Researchers select the AAV vector that evidence suggests is best suited for the disease being studied and the cells they want to target. 

What studies have been done to date using an AAV9 vector?

AAV9 is one of the most extensively studied AAV vectors in gene therapy. It has been evaluated in laboratory research, animal studies, and human clinical trials because of its ability to deliver genes to a variety of tissues, including the brain, spinal cord, heart, and muscles.

Clinical studies using AAV9 have investigated treatments for conditions such as:

• Spinal muscular atrophy (SMA)
• Duchenne muscular dystrophy (DMD)
• X-linked myotubular myopathy (XLMTM)
• Pompe disease
• Several inherited neurological and metabolic disorders

Some AAV9-based gene therapies have been approved for clinical use, while many others are being evaluated in clinical trials. Results from these studies continue to improve our understanding of the potential benefits and risks of AAV9-based gene therapy. 

What is a first-in-human clinical trial?

A first-in-human (FIH) clinical trial is the first time an investigational treatment is given to people after it has shown promising results in laboratory and animal studies.

The main goals of a FIH trial are to:

• Evaluate the safety of the investigational therapy 
• Identify possible side effects 
• Determine an appropriate dose 
• Learn how the therapy behaves in the body 

These early studies usually involve a small number of participants and are closely monitored by researchers and regulatory authorities. Participants receive regular medical evaluations and safety monitoring throughout the study. For gene therapies, participants are often followed for months or years after treatment so researchers can monitor long-term safety and understand how well the therapy continues to work. While participants may experience a benefit, the primary purpose of a FIH trial is to collect information that will help determine whether the therapy should move forward into larger clinical studies.

MSD Study Team

Principal Investigators 

Laura Adang, MD, PhD, MSTR

Rebecca Ahrens-Nicklas, MD, PhD

Clinical Data Coordinating Center

The Duke Clinical Research Institute

IND Sponsor

National Center for Advancing Translational Sciences (NCATS)