FDA clears Phase 1 trial of GC1130A for Sanfilippo type A
Therapy should bypass blood-brain barrier to break down heparan sulfate
GC Biopharma and Novel Pharma plan to initiate a Phase 1 clinical trial this year to test the safety and tolerability of GC1130A, an investigational enzyme replacement therapy that the companies are developing for Sanfilippo syndrome type A.
The announcement follows the U.S. Food and Drug Administration (FDA) clearing an investigational new drug (IND) application for clinical testing of GC1130A, which is designed to supply the enzyme that’s faulty in this form of Sanfilippo syndrome.
“The IND clearance for GC1130A marks a significant milestone in our mission to bring hope to patients and families affected by Sanfilippo [syndrome],” according to a GC Biopharma press release, which noted the company is “committed to advancing” into human testing.
The four types of Sanfilippo syndrome are caused by mutations in genes that provide instructions for producing enzymes involved in breaking down heparan sulfate, a large sugar molecule.
In type A, the most common and severe type of Sanfilippo, mutations in the SGSH gene result in low or no sulfamidase activity. Partially broken down heparan sulfate then builds up to toxic levels in cells, particularly nerve cells in the brain and spinal cord, disrupting their function.
Treatment options help manage symptoms, which start to show during early childhood and include behavioral challenges, developmental delay and loss of previously acquired skills, trouble falling and staying asleep, and intellectual disability.
What is GC1130A?
GC1130A consists of lab-made version of human sulfamidase, also known as heparan N sulfatase. Delivered via an intracerebroventricular injection into the brain’s ventricles, a network of four cavities filled with fluid, GC1130A should bypass the blood-brain barrier that would otherwise limit its distribution into the brain and spinal cord, where it’s most needed to break down heparan sulfate.
In a mouse model of Sanfilippo syndrome type A, a single or multiple injections of GC1130A reduced heparan sulfate in the brain and cerebrospinal fluid, which flows around and cushions the brain and spinal cord.
Mice treated with GC1130A were significantly more active than placebo-treated mice when allowed to freely explore an open-field chamber, suggesting the therapy could offer potential benefits to patients.
GC1130A has been granted rare pediatric disease status in the U.S., and orphan drug status in the U.S. and Europe. The designations encourage the development of treatments for rare diseases by offering certain incentives, such as market exclusivity and financial benefits.
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