Drug discovery
11
drugs
With orphan designations
Overview
Krabbe disease is a rare autosomal recessive lysosomal disorder caused by GALC gene mutations, leading to galactocerebrosidase deficiency and toxic psychosine accumulation. This results in progressive demyelination of the CNS and PNS. Infantile-onset (85-90% of cases) manifests as irritability, spasticity, and developmental regression before age 6 months, with death typically by age 2–3 years. Late-onset forms present with gait disturbances, neuropathy, and vision loss, progressing to death within 10 years of diagnosis [1][5][6][9][14].
Burden
Clinical: 90% of infantile patients die by age 2; late-onset forms cause cumulative disability (blindness, paralysis) [1][6][10][14].
Economic: $51.5M annual hospitalization charges for 98 US patients (2016 data); 260 inpatient admissions/3-year period [2].
Psychosocial: High caregiver burden due to rapid neurological decline; stem cell transplant mortality reaches 15–20% [3][10][13].
Therapies
HSCT/Cord blood transplant: Only disease-modifying option; most effective if performed pre-symptomatically (≤30 days old). Stabilizes cognition but does not reverse existing damage [3][7][11][19].
Supportive care: Anticonvulsants, muscle relaxants, and enteral feeding support [9][13][15].
Experimental therapies: Intrathecal AAV9 gene therapy restores GALC activity in preclinical models, extending survival 7-fold in animal studies [11][19].
Categories: rare genetic diseases, rare inborn errors of metabolism, rare neurological diseases, rare ophthalmic disorders, rare transplant-related disorders
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
recombinant serotype 9 adeno-associated virus (AAV) encoding a human galactosylceramidase (GALC) transgene (hGALC) | gene therapies | FDA | 2024-10-29 | — | Elpida Therapeutics SPC |
Recombinant serotype 9 adeno-associated virus encoding a codon-optimized human galactosylceramidase (GALC) transgene (hGALCopt2) | gene therapies | FDA | 2022-02-10 | — | Neurogene Inc. |
Adeno-associated virus serotype rh10 containing the human GALC gene | gene therapies | EMA | 2021-10-15 | — | Forge Biologics Europe S.L. |
Gemfibrozil | small molecules | FDA | 2021-08-30 | — | Polaryx Therapeutics, Inc. |
Adeno-associated virus serotype hu68 containing the human GALC gene | gene therapies | EMA | 2021-03-26 | — | FGK Representative Service GmbH |
adeno-associated virus serotype rhesus 10 vector expressing the human galactocerebrosidase (GALC) gene | gene therapies | FDA | 2021-02-10 | — | Forge Biologics, Inc. |
Trans-Cinnamic Acid | gene therapies | FDA | 2021-02-03 | — | Polaryx Therapeutics, Inc. |
a non-replicating recombinant adeno-associated virus serotype hu68 vector, containing a transgene encoding the human galactosylceramidase (GALC) enzyme | gene therapies | FDA | 2020-10-22 | — | GEMMA Biotherapeutics |
ibudilast | small molecules | FDA | 2015-06-01 | — | MediciNova, Inc. |
recombinant human galactocerebrosidase (rhGALC); | proteins | FDA | 2011-12-12 | — | Chiesi USA, Inc. |
RECOMBINANT HUMAN GALACTOCEREBROSIDASE [Galaczym] | proteins | EMA | 2011-09-27 | — | Chiesi Farmaceutici S.p.A. |