Krabbe Disease is a rare neurodegenerative disorder caused by mutations in the galactocerebrosidase (GALC) gene. Advancements in Krabbe newborn screening are making early diagnosis possible.
Image Source: Unsplash
Krabbe disease affects approximately 1-2.5 in 100,000 people in the United States. It is characterized by autosomal recessive mutations in the GALC gene, which is responsible for breaking down certain types of sphingolipids, including psychosine. Without functional GALC, psychosine accumulates in cells, leading to the destruction of myelin in the brain and peripheral nervous system.
Patients typically manifest symptoms in infancy, displaying irritability, feeding difficulties, increased muscle tone, and developmental delays. If left untreated, the disease rapidly progresses, leading to difficulty breathing, seizures, vision and hearing loss, and eventual death.
Newborn Screening
Early diagnosis is crucial in the treatment of Krabbe disease. Unfortunately, healthcare providers often do not detect the disease until after significant symptoms have appeared. As a result, patients typically have a poor prognosis, with most infantile patients dying by age two if left untreated. Recently, Krabbe disease was added to the Recommended Uniform Screening Panel (RUSP), helping to identify affected infants before symptoms manifest and provide life-saving treatments like hematopoietic stem cell transplantation (HSCT) and gene therapy.
Standard of Care
HSCT has been the standard of care for Krabbe disease. This procedure involves replacing the patient’s faulty cells with healthy donor cells, which can produce the missing GALC enzyme. HSCT has been shown to stabilize cognitive decline and significantly improve long-term neurological outcomes when performed before symptom onset.
However, HSCT does not correct the peripheral neuropathy associated with Krabbe disease, which progresses as the patient grows. This limitation has prompted the development of new treatment approaches like gene therapy.
Gene Therapy
Promising results in the treatment of Krabbe disease have been shown in clinical trials and gene therapy. More specifically, the development of FBX-101, an adeno-associated viral (AAV) gene therapy designed to address peripheral nerve disease not corrected by HSCT.
Data from Krabbe patients treated with HSCT and FBX-101 gene therapy in clinical trials have demonstrated safety and efficacy post-FBX-101 systemic administration. Five patients have received FBX-101, all of whom were identified through newborn screening. The therapy has shown increased GALC expression, reduced psychosine levels, normalized motor function, and corrected brain white matter growth.
The FDA has granted FBX-101 Fast Track Designation, Orphan Drug Designation, and Rare Pediatric Disease Designation, recognizing its potential to address an unmet medical need. Additionally, the European Medicines Agency (EMA) has granted FBX-101 Orphan Drug Designation and Priority Medicines (PRIME) designation.
To learn more about the latest clinical trial testing the safety and efficacy of FBX-101 go to https://clinicaltrials.gov/study/NCT05739643
For more information on Krabbe disease and other rare neurological diseases, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/