Krabbe Disease

Krabbe disease is a rare genetic neurologic disorder that presents early in life

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Disease Background

  • Krabbe disease is an inherited disorder that destroys the protective coating (myelin) of nerve cells, resulting in progressive damage to both the brain and nervous system

  • Krabbe disease is an autosomal recessive disorder, which simply means that both parents had the abnormal gene and the affected child received both copies

  • Infants may present with loss of acquired milestones, staring episodes, peripheral neuropathy, seizures, blindness, and deafness

  • The two most common forms of Krabbe disease are Early Infantile (the most severe form) and Late Infantile, which occurs later in infancy

Early Infantile Krabbe Disease
  • Typically manifests before 6 months of age

  • Accounts for up to 70% of cases

  • Highly predictable course of disease

  • Rapidly progresses to loss of acquired milestones, severe weakness, seizures, blindness, and deafness

  • Median survival to 2 years of age

Late Infantile Krabbe Disease
  • Typically manifests between 6 and 36 months of age

  • Accounts for up to 30% of cases

  • More variable course of disease

  • Presents symptoms similar to early-infantile form

  • Median survival to approximately 5 years of age

Toddler kissing an infant sibling

Mechanism Of Disease

In Krabbe disease, two mutated copies of the GALC gene result in little to no production of a critical enzyme called galactocerebrosidase.

  • Galactocerebrosidase breaks down certain fats, including galactosylceramide and psychosine

  • Accumulation of psychosine affects the myelin-producing cells in the central nervous system, resulting in widespread death of these cells

  • Without myelin, nerves in both the brain and other parts of the nervous system cannot transmit signals properly, leading to the signs and symptoms of Krabbe disease

Incidence

Passage Bio believes that the incidence of Krabbe disease is estimated to be 2.6 in 100,000 births in the United States, which is higher than the reported levels in literature

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Statistics are based on analysis of data from six states that are currently conducting mandatory screening for Krabbe disease at birth

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Patients with infantile Krabbe disease may be eligible for enrollment in clinical trials of investigative therapies, so early diagnosis is critical. Caregivers should reach out to their healthcare professional to learn more.

Management

  • There are no approved disease-modifying treatments for Krabbe disease

  • In the US, hematopoietic stem cell transplantation (HSCT) has been increasingly used in children who are presymptomatic or have mild symptoms. In early infantile Krabbe disease, patients with more than mild symptoms do not appear to benefit, so HSCT is typically started in the first 30 days of life*

  • Passage Bio is investigating a novel gene therapy, PBKR03, for the treatment of Krabbe disease

Learn more about PBKR03.

* It is important to note that in addition to the well-described morbidities and mortality associated with HSCT, predominantly related to post-treatment immunosuppression, there is a growing appreciation of an unmet need post-HSCT in children with Krabbe. Specifically, these children continue to have gross and fine motor deficits.

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Key collaboration that facilitates genetic screening and counseling

Invitae, a leading medical genetics company that facilitates genetic testing and supports early identification of GM1 gangliosidosis and Krabbe disease. Our partnership involves providing clinical trial information to clinicians and patients.

Learn more at invitae.com.

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See what’s on the horizon

Learn about a therapy we’re studying for Krabbe disease.

Review Our Pipeline

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Take a deeper dive

Learn more about the science behind our work.

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