Canavan Disease Drug Discovery Service

Canavan disease (CD) is a rare neurodegenerative disease that often occurs in infancy/adolescence. One of its common features is the progressive damage of nerve cells and the loss of white matter in the brain caused by significantly elevated NAA levels, which may eventually lead to intellectual disability, macrocephaly, spasms and even premature death. There is no particularly effective treatment for CD at present, which makes the research on the pathogenesis and mechanism of action of CD essential. As a leading biotech company with several years of experience, Creative Biolabs offers reliable and cutting-edge CD Drug Discovery Services for our global clients, whether you are looking for a one-stop solution, or want to be assisted in specific steps, we will develop a detailed project for you to meet your every demand.

Background and Pathology of CD

CD is a relatively common infantile encephalopathy inherited through autosomal recessive inheritance. Its causative gene, the aspartate acylase (ASPA) gene, is 29 in length and includes 6 exons. Mutations in ASPA result in reduced activity of aspartate acylase, which cannot efficiently catalyze NAA to aspartate and acetate, and causes NAA accumulation in the brain. Therefore, significantly increased NAA levels in plasma, urine and cerebrospinal fluid have also become the basic signs of CD pathogenesis. In addition, CD also has abnormal myelination, the occurrence of vacuolar astrocytes and spongy white matter as characteristics of malnutrition. However, the specific mechanism of accumulated NAA leading to CD remains undetermined.

Medicalimageology of CD

There are many approaches for CD diagnosis and identification. Here at Creative Biolabs, reliable conclusions can be drawn by observing elevated levels of NAA in urine, or using methods such as genome sequencing, MRI, MRS, or ASPA mutation analysis to determine CD at the genetic and molecular level levels. We can also perform neuroimaging to show characteristic attenuation of white matter with CT scans.

Fig 1. MRI and MRS for CD diagnosis. (Gowda, 2020)

Intervention of CD

Since the specific pathogenesis of CD has not yet been elucidated, there is still no effective cure for CD, but experimental therapies are being developed. Ongoing CD studies include diet control, lithium citrate administration, stem cell transplantation, lentivirus/CRISPR-mediated gene transduction, or intraparenchymal adeno-associated virus (AAV)-Aspa vector administration, but there has been no success in reversing or preventing the progression of CD. However, we believe that with the comprehensive and reliable services Creative Biolabs provides, you may develop successful and effective CD antagonists more easily. In addition to the screening and identification of drug molecules, we also provide tissue sections, immunostaining, directional transplantation, gene sequencing/knockout, gas chromatography/mass spectrometry and imaging examinations. These experiments can help you more comprehensively analyze and identify the activity and function of the drug to be tested.

Fig 2. Reduced vacuolation in the ASPA iNPC-transplanted CD (Nur7) mouse brains. (Feng, 2020)

Our Services

CD is one of the most common degenerative encephalopathies in infancy with no effective intervention approaches. Extensive pathological studies and molecular analysis of CD are necessary for a better understanding of its nature and pharmacological studies. With our outstanding R&D team, Creative Biolabs now offers professional one-stop solution services for CD to our worldwide clients. Our seasoned scientists are always ready to offer first-class assistance including in vivo and in vitro model construction, determination of changes in NAA content, tissue sectioning and imaging analysis of organs of interest, to best facilitate our clients' research goals. Whether you are looking to use CD models to study malnutrition, decipher the pathogenesis of CD through histological and molecular imaging, study symptoms through genetic intervention, or develop and test drug and inhibitory efficacy, no matter what stage of research you are in, we can formulate solutions and provide services for you through cutting-edge and reliable technology platforms. Please feel free to contact us with our specialist for further information.

References

1. Gowda, V.K.; et al. Canavan Disease: clinical and laboratory profile from southern part of India. Annals of Indian Academy of Neurology, 2020, 10: 347-349.
2. Feng, L.Z.; et al. Cell-based therapy for Canavan Disease using human iPSC-derived NPCs and OPCs. Adv. Sci, 2020, 7: 2002155.