Sanfilippo A enzyme replacement JR-441 test to begin this year

JCR Pharmaceuticals is finalizing trial protocol; recruitment to start this year

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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JCR Pharmaceuticals has won permission from officials in Germany to start a Phase 1/2 clinical trial of JR-441, an experimental therapy designed to deliver to the brain a working version of the enzyme that’s missing in Sanfilippo syndrome type A.

The Paul-Ehrlich Institute (PEI), an agency of the German Federal Ministry of Health, has accepted an application to start the trial, JCR announced in a press release. The company is finalizing the trial protocol to meet regulatory requirements and intends to begin recruiting patients in the third quarter of this year.

Sanfilippo syndrome type A is typically the most severe form of the disease and is marked by symptoms that become apparent in early childhood. It’s caused by mutations in the gene SGSH, which provides instructions for making an enzyme called heparan N-sulfatase, or N-sulphoglucosamine sulphohydrolase.

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What is JR-441 and how does it work?

Like other types of Sanfilippo, type A is characterized by the toxic buildup in the brain of the sugar molecule heparan sulfate. Normally, the heparan N-sulfatase enzyme breaks this sugar molecule down, but without a working version of it, the molecule builds up, damaging the brain and driving the progressive symptoms that characterize the disease.

Delivering a healthy version of the enzyme into the brain could be an effective strategy for treating Sanfilippo A. One impediment to delivering a therapy to the brain is the blood-brain barrier (BBB), which regulates what substances in the blood are able to get into the brain. This is important for protecting it from infections and toxins, but it can also make it difficult to get therapies where they’re needed.

To get around this problem, JR-441 contains a lab-made version of the enzyme that’s attached to an antibody that will stick to a BBB protein called the transferrin receptor. Normally, the transferrin receptor is used for getting iron across the BBB and into the brain. By hijacking this system, JR-441 would allow the therapeutic enzyme to be transported across the BBB into the brain.

The experimental therapy was developed using JCR’s proprietary J-Brain Cargo BBB-penetrating technology and has shown promise for treating Sanfilippo A in preclinical studies, according to the company.