Canavan Disease (CAND)
Canavan disease (CAND) is a rare genetic neurological disorder characterized by the spongy degeneration of the white matter in the brain. With our company's profound expertise in CAND research, we are well-equipped to offer tailored solutions and comprehensive support to facilitate your research process from CAND therapy development to therapy commercialization.
Introduction to CAND
CAND is an uncommon and highly distressing neurodegenerative condition that predominantly impacts infants. It is distinguished by the gradual deterioration of nerve cells and the depletion of white matter in the brain. This disorder detrimentally affects the brain, spinal cord, and peripheral nerves, posing substantial difficulties for both affected individuals and their families. CAND is relatively rare. The estimated incidence of severe CAND in the non-Jewish population is approximately 1:100,000. If both parents are of Ashkenazi Jewish descent, the birth rate is 1:6,400 to 1:13,500.
Fig. 1 Pathophysiology of CAND. (Wei, Huijun, et al., 2022) Pathogenesis of CAND
CAND arises from genetic mutations in the ASPA gene, which encodes the production of the enzyme aspartoacylase. When there is a deficiency in aspartoacylase, it leads to the build-up of N-acetyl aspartate (NAA), a substance that interferes with the normal growth and development of myelin sheath. This disruption in myelin sheath formation is a key factor in the progression of the disease.
Enzyme Aspartoacylase
The enzyme aspartoacylase plays a crucial role in the breakdown of N-acetylaspartate (NAA) in the brain. NAA is a naturally occurring molecule found in high concentrations in the brain's white matter. Aspartoacylase helps catalyze the cleavage of NAA into aspartate and acetate.
ASPA Gene
The ASPA gene is responsible for providing instructions to produce the enzyme aspartoacylase. This gene is located on chromosome 17q21. Mutations in the ASPA gene can lead to a deficiency or complete absence of the enzyme aspartoacylase. This deficiency results in the accumulation of NAA, which is toxic to the myelin-forming cells called oligodendrocytes.
Therapeutics Development of CAND
Developing therapeutics for CAND aims to address the underlying pathogenic mechanisms and provide potential therapeutic options for affected individuals.
- Targets of CAND Therapy Development
| Target | Description |
|---|---|
| Aspartoacylase Function Restoration Pathways | CAND is caused by mutations in the ASPA gene encoding aspartoacylase. Gene therapy approaches, such as viral vector-mediated gene delivery, hold promise in correcting the genetic defect and restoring enzyme activity. For example, adeno-associated viruses (AAVs) can be used to deliver therapeutic genes to the brain. |
| N-acetyl aspartate (NAA) Level Reduction Pathways | Excessive NAA accumulation is believed to contribute to the neurotoxicity observed in CAND. Reducing NAA levels is an important strategy for CAND therapy development. Small molecule inhibitors targeting N-acetyltransferase, the enzyme responsible for NAA synthesis, are being explored to reduce NAA levels. These inhibitors aim to normalize NAA metabolism and mitigate the neurotoxic effects associated with NAA accumulation. |
- Types of CAND Therapy Development
- Gene Therapy Development
The delivery of functional copies of the ASPA gene into affected cells aims to restore the production of aminoacylase 2 and normalize NAA metabolism. Viral vectors, such as AAVs, are commonly used as gene delivery vehicles due to their ability to efficiently target specific cell types in the brain.
- Small Molecule Therapy Development
Small molecule therapies can act as inhibitors of N-acetyltransferase, the enzyme responsible for NAA synthesis, or as activators of NAA degradation enzymes. Small molecules can be designed to target specific steps in NAA metabolism and potentially reduce the neurotoxic effects associated with NAA accumulation.
- Gene Therapy Development
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 CAND.
- CAND Diagnostic Development Services: Elevated urinary NAA levels are a reliable biomarker for CAND. Our company offers diagnostic development services to help accurately detect the levels of CAND biomarkers.
- CAND Therapeutic Development Services: 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. Our AAV vector development platform, specifically tailored for CAND gene therapy, has proven to be a highly effective strategy.
- CAND Animal Model Development Service: To support the preclinical research and development of CAND therapies, we offer CAND animal model development services to facilitate your pharmacokinetics study and drug safety evaluation.
| Genetically Engineered Models | ||||
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| Gene editing and other advanced technologies are employed to introduce, remove, or modify specific genes in the animal's genome, facilitating the construction of animal models for CAND. Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models for CAND therapeutic research. | ||||
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| Optional Species | Mice, Zebrafish, Rats, Non-human Primates, Others | |||
No matter what stage of research you are at, we can provide you with corresponding research services. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Wei, Huijun, et al. "The pathogenesis of, and pharmacological treatment for, Canavan disease." Drug Discovery Today 27.9 (2022): 2467-2483.
- Fröhlich, Dominik, et al. "Dual-function AAV gene therapy reverses late-stage Canavan disease pathology in mice." Frontiers in molecular neuroscience 15 (2022): 1061257.
- Mersmann, Nadine, et al. "Aspartoacylase-lacZ knockin mice: an engineered model of Canavan disease." PLoS One 6.5 (2011): e20336.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.