Each year, around 24,000 women in the US lose a pregnancy. One reason for this unfortunate occurrence are metabolic disorders, one of which is known as Sly syndrome and is caused by a single genetic mutation. In Sly syndrome, the body’s cells lack an enzyme necessary for proper cell function. Many fetuses with this condition die before birth but those that survive are treated with regular injections of the lacking enzyme. Unfortunately, patients can eventually develop an immune response to these injections and it cannot enter the brain after birth.
However, a team of researchers at UCSF are looking at exploring a potential treatment that could be delivered in-utero. In a CIRM supported study, Dr. Tippi Mackenzie and Dr. Quoc-Hung Nguyen transplanted blood-forming stem cells from normal mice into fetal mice carrying the genetic mutation for Sly syndrome. The researchers were most interested to see whether these cells could reach the brain, and whether they would change into cells called microglia, immune cells that originate from blood-forming stem cells. In a normally developing fetus, once matured, microglia produce and store the necessary enzyme, as well as regulate the immune environment of the brain.
The researchers found that the stem cells were able to engraft in the brain, liver, kidney, and other organs. Furthermore, these stem cells were able to eventually turn into the appropriate cell type needed to produce the enzyme in each of the organs.
In a press release, Dr. Mackenzie talks about the impact that this potential treatment could have.
“This group of vulnerable patients has been relatively ignored in the fetal surgery world. We know these patients could potentially benefit from a number of medical therapies. So this is our first foray into treating one of those diseases.”
In the same press release, Dr. Nguyen talks about the impact of the results from this study.
“These exciting findings are just the tip of the iceberg. They open up a whole new approach to treating a range of diseases. At the same time, there’s also a lot of work to do to optimize the treatment for humans.”
The next step for Dr. Mackenzie is to apply to the U.S. Food and Drug Administration to launch a clinical trial of enzyme replacement therapy that will ultimately enroll patients with Sly syndrome and related metabolic disorders.
This approach is similar to a CIRM funded trial conducted by Dr. Mackenzie that involves a blood stem cell transplant in utero.
The full results to this study were published in Science Translational Medicine.