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Norrie disease (ND), a multifactorial genetic condition, affects vision and hearing. At Protheragen, our team of experts has extensive experience in developing comprehensive diagnostics and therapeutic solutions for Norrie disease.
Norrie disease (ND) is classified as an uncommon X-linked recessive condition that presents itself with bilateral blindness at birth and continuous sensorineural hearing loss. The disorder results from genetic mutations in the Norrie disease pseudoglioma (NDP) gene which is responsible for producing a protein known as norrin. This protein is highly significant in developing the retinal blood vessels along with the inner blood-retinal barrier. Disruptions in the NDP gene lead to abnormalities in the vascular development of the retina, which causes hypoxia and tractional retinal detachment. This complication is the reason behind being blind at birth. Furthermore, cases are most of the time bound to experience progressive hearing loss and at times cognitive dysfunction, alongside other psychiatric symptoms.
Fig.1 Case studies of systemic delivery of AAV9. NDP therapeutics. (Pauzuolyte V., et al., 2023)
Genetic Testing
The best option for Norrie Disease diagnostic evaluation is genetic testing, which consists of identification of mutations in the NDP gene by means of targeted Sanger sequencing or whole-exome sequencing. Amplification methods for microdeletions and microduplications such as MLPA as well as chromosomal microarray may also reveal deletions or duplications in the NDP and surrounding regions.
Biochemical Analysis
The biochemical analysis of cerebrospinal fluid (CSF) can detect changes that correlate with Norrie Disease. Biogenic amines and serotonin and some of their metabolites are measured by high-performance liquid chromatography (HPLC). One case study involving a patient with Norrie Disease has revealed that individuals may have almost no imaginative concentrations of these metabolites, which implies a profound insufficiency of monoamine oxidase (MAO) activity.
The ability of gene therapy to resolve Norrie Disease by functional NDP cDNA transfer to affected tissues appears to be hopeful. The human NDP gene has been packaged in adeno-associated viral (AAV) vectors like AAV9, which has been administered to a mouse model of Norrie Disease. Moreover, AAV9 NDP gene intravenous administration has proved efficacious in rescuing retinal dysfunction and hearing impairment, paving the way for future therapeutic utilization.
The pathophysiological basis of Norrie Disease is of great importance currently and attempts are being made in many human trials using non-single gene therapies as well as small molecules to treat it. These trials have the aim of finding the best therapeutic agents to halt or decelerate the disease and improve the prognosis.
At Protheragen, we offer comprehensive services for the development of diagnostics and therapeutics for Norrie Disease. Our services include:
Ndptm1Wbrg Mouse Models: abnormal retinal vascularization and progressive hearing loss
ND Gene Mutant Mouse Models: the murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with its human counterpart.
Protheragen works with clients to design therapeutic strategies that target the underlying genetic and biochemical abnormalities associated with Norrie Disease. If you are interested in our services, please feel free to contact us.
Reference
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