Active not recruitingPHASE1, PHASE2INTERVENTIONAL

Gene Therapy With Modified Autologous Hematopoietic Stem Cells for Patients With Mucopolysaccharidosis Type II

This study is looking into a new gene therapy for young boys with Mucopolysaccharidosis Type II (MPS II), or Hunter Syndrome. This is a genetic condition where the body doesn't produce an important enzyme needed to clear out specific sugar chains, causing them to build up and harm organs, including the brain. Current treatments help manage some symptoms but don't reach the brain effectively. This new therapy involves taking the child's own cells, adding a working copy of the missing enzyme's gene, and putting them back. The goal is for the body to then make the enzyme continuously. Doctors will closely monitor safety and how well it works over two years. This is the first time this specific gene therapy will be tested in humans.

At a glance

Status

Active not recruiting

Phase

PHASE1, PHASE2

Sponsor

University of Manchester

Enrolment target

Start

01 Jun 2023

Estimated completion

01 Jul 2028

Mucopolysaccharidosis II

What is this study about?

Mucopolysaccharidosis Type II, often called MPS II or Hunter Syndrome, is a rare illness that mostly affects boys. It's caused by a faulty gene that means the body can't make a special enzyme called iduronate-2-sulfatase (IDS). This enzyme is like a tiny cleaner, breaking down certain sugar chains that are naturally found in our bodies. Without enough of this enzyme, these sugars build up inside cells and organs, causing damage over time. This can lead to various health issues, including problems with development and physical abilities, and can also affect the brain.

Currently, the main treatment involves giving the missing enzyme through regular drips into the bloodstream. While this can help with some of the body's problems, it doesn't usually reach the brain, so it can't help with brain-related symptoms. This new study is exploring a different approach: gene therapy. This therapy aims to put a working copy of the IDS gene into the child's own cells. The idea is that once these cells have the correct gene, they can start producing the missing IDS enzyme themselves, and hopefully, keep doing so for a long time. This could mean the body has a constant supply of the enzyme it needs, potentially helping more widely, including in the brain.

To do this, some of the child's own special blood-forming cells are collected. A healthy copy of the gene is then added to these cells in a laboratory. Once modified, these cells are given back to the child through an infusion. These changed cells then travel to the bone marrow and start making new blood cells that carry the IDS enzyme around the body. The main purpose of this study is to see if this new gene therapy is safe for young children with MPS II and if it can help their bodies make enough of the missing enzyme to improve their symptoms. Patients will be carefully watched for at least two years to understand these effects.

Key takeaways

Targets boys aged 3-22 months with MPS II (Hunter Syndrome).
Uses the child's own cells, modified with a healthy gene, to make the missing enzyme.
Aims to provide a continuous supply of the IDS enzyme, potentially helping the brain.
This is a first-in-human trial, carefully checking safety and effectiveness.
Requires a commitment to at least two years of close follow-up.
Current standard treatment (ERT) doesn't effectively treat brain symptoms.

Who may be eligible?

This study is looking for a small number of young boys with MPS II to take part. To be considered, boys must be between 3 months and 22 months old when they are screened for the study. Doctors will also check their development to make sure they are either developing normally or have only mild developmental delays.

To be eligible, the boy's family history or genetic tests must show a type of MPS II that is expected to affect the brain. He must also have very low levels of the IDS enzyme. It's important that he's generally stable and healthy enough to handle the study's requirements, including clinic visits. Parents or guardians must be willing to give permission and commit to all the necessary appointments and follow-up for the study's duration.

Boys cannot join if they have had other stem cell or gene therapies before, or if they are currently taking part in another drug trial. Those with poorly controlled seizures or certain types of gene mutations that usually lead to a milder form of MPS II (without brain involvement) would also not be able to participate. If the child is on certain medications that could interfere with the study results, they might also be excluded.

Quick self-check

Is your child a boy aged between 3 and 22 months?
Does your child have MPS II (Hunter Syndrome)?
Has your child *not* had any other gene therapy or stem cell treatments before?
Is your child's MPS II type expected to affect the brain (severe form)?
Are you able to commit to several clinic visits and follow-up over at least two years?

This is a guide only — the research team will confirm whether you can take part.

What does participation involve?

If your child is eligible for this study, taking part would involve several steps. First, doctors will collect some of your child's own blood-forming cells. To do this, your child will be given some medicine to encourage these special cells to move from the bone marrow into the bloodstream, where they can be collected like a blood donation. In a lab, a working copy of the missing gene will be added to these collected cells. These modified cells will then be given back to your child through a drip, similar to a blood transfusion.

After receiving the gene therapy, your child will have regular check-ups and assessments over at least two years. These visits are very important to make sure the therapy is safe and to see how well it's working. This includes looking for any side effects and checking if the body is making more of the IDS enzyme. You'll need to commit to attending all these clinic appointments as required by the study plan. The total duration of active follow-up will be at least two years, but further long-term follow-up beyond this initial period might also be requested.

Potential risks and benefits

This is a very early-stage trial, so while there's hope for an ongoing supply of the missing enzyme and potential for widespread improvement, including in the brain, the full benefits are not yet known. As with any new treatment, especially gene therapy, there are potential risks, such as side effects from the cell collection process, reactions to the infusion, or unforeseen effects from the modified cells. The study is carefully designed to monitor safety very closely. Remember, participation is completely voluntary; you have the right to withdraw your child from the study at any time without affecting their medical care.

Locations (1)

Manchester University Foundation Trust
Manchester, United Kingdom

Common questions

What is MPS II?

MPS II, or Hunter Syndrome, is a genetic condition where the body can't break down certain sugars, which then build up and cause health problems.

How does this gene therapy work?

It involves taking your child's own cells, adding a correct copy of the missing gene to them in the lab, and then putting these modified cells back into your child's body so they can make the missing enzyme themselves.

Will this therapy cure MPS II?

This is an early study to see if the therapy is safe and can help. It aims to provide the missing enzyme, but it's too soon to say if it can be a cure.

How long will my child be followed after the treatment?

Your child will be closely monitored for at least two years after receiving the gene therapy to check for safety and how well it's working.

What is the age limit for joining the study?

Boys need to be between 3 months and 22 months old at the time of screening to be considered for this study.