Why is ERT Used Before Stem Cell Transplant in MPS I?

If your baby is scheduled for a hematopoietic stem cell transplant (HSCT), you might be wondering why they still need to undergo weekly enzyme replacement therapy (ERT) infusions. It can feel much more than just confusing—it is emotionally and physically exhausting to put a tiny infant through weekly IVs when a transplant is already planned. The reason your care team recommends this is that ERT acts as a vital “bridge to transplant.” It rapidly improves your baby’s physical health, helping to optimize their condition so they can better tolerate the intensive transplant procedure ^[1][2].

Clearing the Buildup to Protect Organs

In MPS I (Hurler syndrome), the body is missing an essential enzyme that breaks down complex sugars called glycosaminoglycans (GAGs). Without this enzyme, these sugars build up inside cells and damage organs. While a stem cell transplant will eventually give your baby a continuous supply of this missing enzyme, it takes time to prepare for the procedure, and even more time for the transplanted cells to start working fully.

ERT provides immediate doses of the missing enzyme. This jump-starts the process of clearing out the built-up sugars in the body ^[1]. One of the most noticeable benefits is the reduction in size of an enlarged liver and spleen ^[3][4]. By shrinking these organs back closer to their normal size, your baby’s body can function much more comfortably and efficiently.

Strengthening the Body for Transplant

The stem cell transplant process is harsh. It requires a conditioning phase, where your baby will receive strong medications like chemotherapy to make room for the new, healthy donor cells. While hearing the word “chemotherapy” is terrifying, the medical team will closely manage and support your baby through this phase. To safely get through it, your baby’s organs must be as strong as possible.

The sugar buildup from MPS I can stiffen the lungs and severely strain the heart, making breathing difficult. ERT leads to rapid improvements in breathing and can stabilize some heart muscle issues ^[1]. While it may not reverse damage to the heart valves, improving your baby’s respiratory health and reducing organ swelling transforms them into a much more stable candidate for the transplant ^[1][5].

What to Expect During the “Bridge” Phase

Typically, this “bridge” phase of weekly ERT lasts anywhere from a few weeks to a few months, depending on how quickly the transplant can be scheduled and how your baby’s body responds to the infusions. Because babies can sometimes have allergic or infusion-associated reactions to the ERT, your care team will monitor them very closely during each session to ensure they are safe.

Why Both Treatments Are Needed

While ERT is incredibly effective at treating the body, the enzymes infused into the blood cannot cross the blood-brain barrier—a protective layer that shields the brain ^[1]. Because ERT cannot reach the brain, it cannot stop the cognitive and neurological decline associated with severe MPS I ^[6].

This is why a stem cell transplant is the ultimate standard of care: the new, healthy immune cells from the donor can travel to the brain and produce the missing enzyme there, protecting your baby’s neurological development ^[6][7]. Evidence also shows that receiving ERT before the transplant does not negatively affect the success of the new donor cells settling into the bone marrow, a process known as engraftment ^[1].

In short, ERT prepares the body to safely endure the transplant, while the transplant protects the brain and provides a lifelong supply of the enzyme. Once the transplant is complete and the donor cells are successfully producing the missing enzyme, the weekly ERT infusions are typically stopped.