Sanfilippo syndrome type A candidate named orphan drug

GC1130A is injected into the brain’s ventricles, bypassing blood-brain barrier

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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The European Medicines Agency (EMA) has granted orphan drug status to GC1130A, an investigational brain-penetrant enzyme replacement therapy that’s in preclinical testing for Sanfilippo syndrome type A.

GC1130A, which is being developed by GC Biopharma with Novel Pharma, was also awarded rare pediatric disease and orphan drug designations in the U.S. last year.

“This EMA designation further underlines the potentials of our collaborative pipeline in addressing the disease pathology mechanism in upcoming clinical trials,” GC Biopharma stated in a press release. The company said it is committed to “expeditiously advancing into clinical trials, acknowledging the urgent, unmet medical needs of Sanfilippo syndrome patients.”

An orphan drug designation is given to medications that target diseases that affect fewer than 200,000 people in the U.S. or no more than five in 10,000 people in Europe. The designation comes with benefits such as fee reductions and exclusive marketing rights for a set time should it be approved.

Sanfilippo syndrome is caused by mutations in genes that provide instructions for making enzymes involved in breaking down heparan sulfate, a large sugar molecule. In Sanfilippo syndrome type A, mutations in the SGSH gene impair sulfamidase enzyme production. As a result, heparan sulfate builds up to toxic levels in cells, particularly nerve cells, interfering with their function.

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Treating Sanfilippo syndrome type A

Treatment is focused on easing symptoms, which include behavioral challenges, developmental delays, and trouble sleeping, usually starting early in childhood and worsening over time.

Preclinical and clinical testing is ongoing for several investigational medications, including enzyme replacement therapy, which provides a working version of the sulfamidase enzyme. This is expected to slow the disease’s progression.

GC1130A is a recombinant (lab-made) version of human sulfamidase made by the ovary cells of Chinese hamsters. The cells are genetically modified by inserting a gene that provides instructions for making the enzyme.

Because it’s delivered directly into the brain’s ventricles (a set of four fluid-filled cavities) by intracerebroventricular injection and bypasses the blood-brain barrier, GC1130A is expected to reach nerve cells in the brain and spinal cord, where the enzyme is most needed.

In preclinical testing in a mouse model of Sanfilippo syndrome type A, a single intracerebroventricular injection of GC1130A reduced heparan sulfate buildup in the brain and the fluid in and around the brain and spinal cord, called the cerebrospinal fluid, for up to 28 days.

The data, presented at the SSIEM annual symposium last year in Jerusalem, also showed that multiple injections of GC1130A at a low, medium, or high dose led to significant heparan sulfate reductions over a placebo.

In an open field test, where mice are allowed to move freely in an arena to determine their overall activity levels, those treated with GC1130A were significantly more active that those on the placebo, suggesting GC1130A’s therapeutic potential.