Krabbe Disease—PBKR03

About PBKR03:

We are developing PBKR03 to treat infantile Krabbe disease, the most common and severe form of Krabbe disease. PBKR03 utilizes a next-generation AAVhu68 capsid to deliver DNA encoding the galactosylceramidase (GALC) enzyme to a patient's cells. PBKR03 will be administered as a single dose by intra-cisterna magna injection into the cerebrospinal fluid.

For more information on the global PBKR03 clinical trial, please click here: Study of Safety, Tolerability and Efficacy of PBKR03 in Pediatric Subjects With Early Infantile Krabbe Disease - Full Text View -

About Krabbe Disease:

Krabbe disease is a rare and often life-threatening lysosomal storage disease that presents early in the patient’s life, resulting in progressive damage to both the brain and peripheral nervous system (PNS). Infants may present with extreme irritability and excessive crying, feeding difficulties, fisted hands, poor head control, stiffness and arching.

The early infantile form of Krabbe disease typically manifests before six months of age and is the most severe form, accounting for 60% to 70% of Krabbe disease diagnoses. In these patients the disease course is highly predictable and rapidly progresses to include loss of acquired milestones, staring episodes, apnea, peripheral neuropathy, severe weakness, unresponsiveness to stimuli, seizures, blindness, deafness and death by two years of age. Late infantile patients present symptoms that are similar to those of early infantile Krabbe disease, with a median survival of approximately five years from onset of symptoms. Late infantile Krabbe disease is defined by onset between seven to twelve months of age. It comprises approximately 10% to 30% of cases and exhibits greater variability in clinical presentation.

Krabbe disease is an autosomal recessive lysosomal storage disease caused by mutations in the GALC gene, which provides instructions for making an enzyme called galactosylceramidase, which breaks down certain fats, including galactosylceramide and psychosine. The myelin-producing cells in the central nervous system and peripheral nervous system are particularly sensitive to the accumulation of psychosine, resulting in widespread death of these cell populations. Without myelin, nerves in both the brain and other parts of the body cannot transmit signals properly, leading to the signs and symptoms of Krabbe disease.

There are no approved disease-modifying treatments for Krabbe disease. There is only supportive care for Krabbe disease including feeding tubes, respiratory support and seizure control until death. Although there is some evidence that human stem cell transplant (HSCT) is beneficial for pre-symptomatic infants with Krabbe disease, there is no established way to predict which patients will become symptomatic.

Furthermore, there are serious risks associated with HSCT, including relatively high rates of mortality. When performed after the onset of overt symptoms in these patients, HSCT provides only minimal neurologic improvement and does not substantially improve survival.

We believe the incidence of Krabbe to be approximately 2.6 in 100,00 births, which is higher than reported incidence levels. Our belief is based on work we have done analyzing data from the six states that currently conduct mandatory screening for Krabbe at birth and those states that haven’t yet implemented such screening.