Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
Leukoencephalopathy (CADASIL) is a condition causing ischemic brain
lesions,which gradually leads to cognitive decline and eventually to
dementia. The disease is caused by mutations in the NOTCH3 gene,
which is exclusively expressed in vascular smooth muscle cells (VSMC),
and which encodes the NOTCH3 protein. In CADASIL patients there is
accumulation of the extracellulair domain of the NOTCH3 protein and
granular osmiophilic material on the surface of degenerating VSMC,
which leads to impaired vascular reactivity and decreased cerebral
blood flow. Currently, there is no treatment for CADASIL patients
available yet.
Although the pathogenesis of the disease is still poorly understood, it
has been shown that, due to the characteristic mutations, misfolding of
the protein occurs resulting in an unequal number of cysteine residues.
Scientists at a Dutch University Medical Center succeeded in reestablishing
an equal number of cysteine residues in the NOTCH3 protein by the exclusion of specific exons from the mRNA. They demonstrated that this reduces or even delays the accumulation of NOTCH3 on the surface of VSMC. This novel finding could eventually lead to the development of gene therapeutic strategies for CADASIL patients.

Innovative Aspects:
Key Benefits:
- New gene therapeutic strategies;
- Unmet need;
- Benefits related to orphan disease status;
- New insights for other autosomal dominant diseases.

 

Patents/Rights: Patent(s) applied for but not yet granted

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