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Trial OKed for Rare Disease Gene Therapy

Nerve cells illustration

(Colin Behrens, Pixabay)

4 Jan. 2021. A start-up biotech company says it received clearance from the Food and Drug Administration to begin a clinical trial of its gene therapy for Krabbe disease. Forge Biologics Inc. in Columbus, Ohio says FDA approved the company’s investigational new drug application, or IND, that in effect allows for trials with patients.

Krabbe disease is a severe genetic neurological condition mainly affecting infants. The disease results from mutations in the galactosylceramidase or GALC gene that provides instructions for enzymes to break down certain fats in the body, including those that regulate production of myelin, the protective coating on neurons or nerve cells in the brain and elsewhere in the body.

Without these enzymes, the fats turn toxic and prevent myelin from forming around neurons, causing damage to nerve cells. Infants under the age of one year with Krabbe disease first show irritability, muscle weakness, and feeding difficulties, and later exhibit difficulty moving, chewing, swallowing, and breathing, as well as vision loss and seizures.

Forge Biologics provides specialized lab space and manufacturing facilities for gene therapies designed to treat inherited diseases. The company specializes in producing treatments with adeno-associated viruses for delivering healthy genes to replace missing or defective genes in patients. Adeno-associated viruses are benign and naturally occurring microbes that infect cells, but don’t integrate with a cell’s genome or cause disease, other than at most mild reactions. As a result, the virus has become a workhorse for delivering healthy or modified genes to treat inherited diseases.

Stem cells plus gene therapy

The company is also developing its own treatments for rare diseases, with its lead product, code-named FBX-101, a gene therapy for Krabbe disease. FBX-101 is based on research by University of Pittsburgh pediatric neurologist Maria Escolar that combines gene therapy with an umbilical cord bone marrow transplant to address central and peripheral nerve degeneration associated with Krabbe disease. In July 2020, as reported in Science & Enterprise, Escolar joined Forge Biologics as chief medical officer at the company’s launch.

Forge says the early- and mid-stage clinical trial will test FBX-101 treatments that begin with blood-forming stem cell transplants in bone marrow, followed by a functioning copy of the GALC gene delivered with adeno-associated viruses, or AAVs. The company says preclinical tests show FBX-101 corrects nerve dysfunction and behavioral impairments in lab animals, as well as improves their survival time. Forge says an institutional biosafety committee and institutional review board also approved the company’s plans for the trial, but a listing for the study is not yet registered on

“This combination approach is extremely exciting because the preclinical data demonstrate significant correction of survival, behavior and neuromuscular function in animal models compared to either transplant or AAV treatment alone,” says Escolar in a Forge Biologics statement. “This is a significant milestone for Krabbe disease families suffering from this deadly disease.”

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