Our
Approach

The standard of care for treating lysosomal disorders today is enzyme replacement therapy (ERT), which slows but does not halt the overall progression of disease and which does not address symptoms of the brain and nervous system in disorders such as Fabry disease, Gaucher disease and Pompe disease.

ERTs were transformative when introduced 30 years ago. We believe that advances in science have put us on the brink of a new paradigm. Gene therapy holds the promise for delivering substantial advances in patient care.

Our personalized therapies start with the patient’s own stem cells.

1. The patient is treated with a widely used combination of medications designed to mobilize or encourage their stem cells to move out of the bone marrow and into the blood. The stem cells are collected through a process called apheresis at a center that specializes in this work.
   • Stem cells are a powerful type of cells with the ability to develop into all the components of a healthy blood system including white blood cells.
   • Apheresis typically involves taking blood from one arm, passing it through a machine that collects the stem cells, and returning the rest of the blood to the other arm.
2. We take the patient’s stem cell collection and enrich for a particular type of cell, called CD34+ cells. These are used to make the therapy because they are capable of taking up residence, or engrafting, in the bone marrow and producing trillions of daughter cells.
3. We introduce a therapeutic gene into the patient’s CD34+ cells in a controlled process called transduction. We insert the gene into the cells using a lentiviral vector. We believe these vectors are effective at integrating the therapeutic gene directly into the stem cells’ DNA.
   • A therapeutic gene, also called a transgene, is a gene designed to produce the specific functional protein the patient lacks. Functionally, it takes the place of the mutated gene that is causing the patient’s disease. The process is called “gene addition therapy.”
   • A vector is a highly modified virus that has been stripped of its pathological elements but retains the ability to deliver a genetic package (in this case, the therapeutic gene) and permanently integrate it into the chromosomes of the patient’s CD34+ cells.
4. Many of the CD34+ cells that were removed from the patient’s bloodstream are now expected to carry the therapeutic gene.
5. These cells are then returned to the patient via a one-time infusion. The cells are expected to engraft in the bone marrow, where they should soon begin dividing to form trillions of new daughter cells, each of which will carry the therapeutic gene. Some of the daughter cells of the CD34+ cells are expected to migrate into the brain, where they will engraft. Over a short period of time, the patient is expected to start to have trillions of cells expressing the functional protein.

Conditioning is a key step in the therapeutic process. It prepares the patient’s body to receive the gene therapy. At AVROBIO, we are committed to a conditioning process that provides each individual with a personalized therapeutic approach. This may include tailoring the therapy with the conditioning agents and dosing regimen most appropriate for the individual.

Learn more

Our gene therapies are investigational and have not been approved by the FDA or any other regulatory agency.

Still have questions?

Watch this video to learn more about gene therapy.

Our investigational therapies are designed with the intent that the therapeutic protein will be available throughout the patient’s body, including the nervous system, either by correcting specialized blood cells, and/or in the plasma available for take-up into other cells, which is called “cross correction.”

Our process is designed to potentially enable widespread engraftment in the brain of microglia cells containing the therapeutic gene. The goal is to address the CNS symptoms that can arise from lysosomal disorders, such as impaired cognition.

Circulating the therapeutic protein in other hard-to-reach areas, such as the bone and muscle, is also crucial to delivering an effective therapy.

In Pompe disease, for instance, our team is using a proprietary technology, known as a GILT tag, intended to facilitate delivery of the protein so it is readily taken up by the muscle. This is crucial for people living with Pompe disease, a progressive disorder that relentlessly erodes neuromuscular control, leading to major muscle weakness.

All our investigational therapies are intended to lead to durable and stable levels of the therapeutic protein throughout the patient’s body, including the nervous system. This feature is designed to address one of the limitations of ERTs.

Immediately after a patient receives an infusion of ERT, his or her body starts to break down the therapeutic enzyme. That’s why people on ERT typically receive biweekly infusions for life; they need to continually replenish their supply of the therapeutic enzyme.

Our investigational gene therapies are designed as a one-time dose. We hope to eliminate the need for chronic treatment.