Scientists from Cincinnati Children’s and the National Institute of Neurological Disorders and Stroke (NINDS) have taken a major step forward in developing a gene therapy for Hurler syndrome, an unusual and often fatal condition that causes extensive organ damage and other complications.

In mice bred to exhibit the inherited human disorder, researchers successfully used engineered blood platelets and bone marrow cells to deliver potentially curative gene therapy. The approach inserted a gene that allowed the cells to produce IDUA, a critical lysosomal enzyme, which resulted in a complete metabolic correction of the disease.

Detailed findings were published online Feb. 3, 2014, in the Proceedings of the National Academy of Sciences (PNAS).

“Our findings demonstrate a unique and somewhat surprising delivery pathway for lysosomal enzymes,” said Dao Pan, PhD, corresponding author and a researcher in the Division of Experimental Hematology and Cancer Biology at Cincinnati Children’s. “We show proof of concept that platelets and megakaryocytes are capable of generating and storing fully functional lysosomal enzymes, which can lead to their targeted and efficient delivery to vital tissues where they are needed.”

Hurler syndrome is one form of a disease more accurately known as mucopolysaccharidosis type I (MPS I). This is one of the most common types of lysosomal storage diseases, in which people do not make an enzyme called lysosomal alpha-L-iduronidase (IDUA).

IDUA helps break down sugar molecules found throughout the body, often in mucus and fluids around joints. Without IDUA, sugar molecules build up and cause widespread tissue damage. Depending on severity, the syndrome can cause deafness, abnormal bone growth, heart valve problems, joint disease, intellectual disabilities and death.

Enzyme replacement therapy can be used to treat the disease, but it is not curative. Bone marrow transplant using hematopoietic stem cells has been tested on some patients, but the potentially risky procedure has had mixed results.

Pan and colleagues – including Roscoe Brady, MD, a researcher at NINDS – engineered human megakaryocytic cells that were capable of overexpressing IDUA.  Once infused, the cells produced large amounts of functional IDUA. They also retained the capacity to cross-correct other cells. The treatment led to a complete metabolic correction of MPS I in most peripheral organs of the mice.

While the latest results are encouraging, the researchers say much more study is needed to determine if the treatment would be safe and effective for human patients.