Researchers have overcome a major challenge to treating brain diseases by engineering an experimental molecular therapy that crosses the blood-brain barrier to reverse neurological lysosomal storage disease in mice.

Posted online in PNAS Early Edition on Feb. 4, the study was led by scientists at Cincinnati Children’s Hospital Medical Center.

“This study provides a non-invasive procedure that targets the blood-brain barrier and delivers large-molecule therapeutic agents to treat neurological lysosomal storage disorders,” said principal investigator  Dao Pan, PhD, a researcher in the Cancer and Blood Diseases Institute at Cincinnati Children’s. “Our findings will allow the development of drugs that can be tested for other brain diseases like Parkinson’s and Alzheimer’s.”

The scientists assembled the large molecular agents by merging part of a fatty protein called apolipoprotein E (apoE) with a therapeutic lysosomal enzyme called a-L-idurondase (IDUA). Then, the team used them to treat lab-cultured human cells and mouse models of the disease mucopolysaccharidosis type I (MPS I).

MPS I is one of the most common lysosomal storage diseases to affect the central nervous system, which in severe form can become Hurler syndrome.  The disease can lead to hydrocephalus, learning delays and other cognitive deficits. If not treated, many patients die by age 10.

In MPS I, cells lack the IDUA enzyme, allowing abnormal accumulation of cellular debris in the brain and other organs. The experimental therapy is exciting because the team found a way to carry supplemental IDUA across the blood-brain barrier. By tagging some apoE components to the IDUA enzyme, the modified protein could attach to endothelial cells and cross through the cells to reach brain tissues.

The scientists are working to further verify whether the therapy can be applied to humans.  They also are testing whether the approach used in the study can be leveraged to develop other therapeutic agents that cross the blood-brain barrier.