Krabbe Disease (KRB)
Krabbe disease (KRB) is a rare and often fatal lysosomal storage disease that causes progressive damage to the nervous system. With our pioneering efforts in KRB research, we are at the forefront of developing cutting-edge diagnostic tools and therapeutics to facilitate the effective management of KRB. As your reliable partner in KRB research, we offer unmatched support to fulfill your scientific research needs.
Introduction to KRB
Krabbe disease (KRB), also known as globoid cell leukodystrophy, is a severe neurological disorder that falls under the category of leukodystrophies. It is characterized by the progressive loss of myelin (the protective covering around nerve cells), resulting in impaired transmission of nerve signals. The most common form of KRB is the infantile form, which usually begins within 12 months of age. 85%-90% of individuals with infantile form show progressive neurological deterioration and die before the age of two years. The global incidence of KRB ranges from 1/100,000 to 1/250,000 live births.
Fig. 1 Mechanisms underlying demyelination and dysmyelination and mechanism-based therapeutic targets for Krabbe disease (Won, Je‐Seong, et al., 2016)Pathogenesis of KRB
KRB is caused by mutations in the GALC gene encoding galactosylceramidase. This enzyme is responsible for breaking down specific fats called galactolipids, including galactosylceramide and psychosine. Mutations in the GALC gene result in a lack of galactosylceramidase activity, leading to the accumulation of galactolipids and subsequent damage to myelin-forming cells. Loss of myelin and impaired nerve signaling results in the characteristic symptoms of KRB, including muscle weakness, difficulty eating, developmental delays, and vision problems.
Diagnostics Development of KRB
Accurate and early diagnosis of KRB is crucial for effective management and intervention strategies. Various diagnostic approaches are employed to identify individuals with KRB, including symptom evaluations, genetic testing, and imaging studies.
Symptom Evaluations
Symptom evaluations involve assessing the symptoms and medical history of the individuals, as well as conducting a thorough physical examination. This lays the foundation for further diagnosis.
Genetic Testing
Genetic testing plays a vital role in confirming the diagnosis of KRB by identifying mutations in the GALC gene. This can be achieved through techniques such as DNA sequencing or targeted mutation analysis.
Imaging Studies
Magnetic resonance imaging (MRI) can provide valuable information about the extent and distribution of myelin loss in affected individuals. This helps detect characteristic abnormalities such as white matter changes in KRB.
Therapeutics Development of KRB
Although there is no known cure for KRB, several types of therapeutic interventions are currently being explored that could potentially benefit individuals with KRB.
| Therapy Type | Description |
|---|---|
| Hematopoietic Stem Cell Transplantation (HSCT) | HSCT involves the infusion of healthy stem cells, typically from a matched donor, to replace the defective cells in the bone marrow of KRB individuals. The transplanted stem cells can differentiate into functional cells that produce the deficient GALC enzyme. HSCT has shown promising outcomes in the infantile form of KRB when performed early in the disease course. |
| Enzyme Replacement Therapy (ERT) | ERT involves the administration of exogenous enzymes, such as GALC, to compensate for the deficient enzyme activity in affected individuals. Researchers are working on optimizing the delivery of GALC to the affected tissues, ensuring its stability, and maximizing its therapeutic efficacy. |
| Gene Therapy | Gene therapy aims to restore defective enzyme activity and prevent the buildup of toxic galactolipids in KRB by introducing functional GALC genes using viral vectors or non-viral methods. |
| Small Molecule Therapies | Researchers are actively screening and testing small molecules to identify potential drug candidates for KRB therapies. This requires a thorough understanding of the molecular mechanisms underlying KRB and the identification of compounds with favorable pharmacokinetic properties. |
Our Services
Drawing upon our deep expertise in biotechnology and extensive experience in the industry, our company offers all-encompassing solutions for diagnostic and therapeutic research dedicated to KRB.
- KRB Diagnostic Development Services: For rare genetic diseases such as KRB, our company offers diagnostic development services and state-of-the-art next-generation sequencing (NGS) products. We are dedicated to assisting you in the development of rapid and point-of-care diagnostic tests for KRB, ensuring accurate and timely detection.
- KRB Therapeutic Development Services: Our services extend beyond diagnostics, and we are also committed to the development of novel therapeutics for KRB. Our company provides a wide range of services for the development of small molecule drug, cell therapy, gene therapy, therapeutic antibody, therapeutic peptide, and therapeutic protein.
- KRB Animal Model Development Service: To support the preclinical research and development of KRB therapeutics, we offer KRB animal models development services to facilitate your pharmacokinetics study and drug safety evaluation.
| Chemical Induction Models | ||
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| By administering spiritine, a toxic metabolite that accumulates in KRB, to animal models, researchers can successfully replicate crucial pathological characteristics seen in this disorder. This methodology enables the study of psycholin's effects on myelin integrity, neuroinflammation, and neurodegeneration. | ||
| Genetically Engineered Models | ||
| Genetic manipulation techniques, such as gene knockout or knock-in, are employed to introduce specific mutations associated with KRB into animal genomes. Our company excels in manipulating the expression or function of genes associated with myelin metabolism to induce KRB-like pathology in animal models. | ||
| Optional Models |
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| Optional Species | Mice, Canines, Others | |
If you are interested in our services, please feel free to contact us for more details and quotation information for related services.
References
- Won, Je‐Seong, Avtar K. Singh, and Inderjit Singh. "Biochemical, cell biological, pathological, and therapeutic aspects of K rabbe's disease." Journal of neuroscience research 94.11 (2016): 990-1006.
- Brites, Pedro, and Monica M. Sousa. "Neurons contribute to pathology in a mouse model of Krabbe disease in a cell-autonomous manner." PLoS Biology 20.7 (2022): e3001706.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.