CADASIL: Causes, Current Care and Treatment Research

CADASIL stands for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. It is an inherited disease of small blood vessels, particularly in the brain. Changes in these vessels can cause small strokes and damage to white matter, the tissue that connects different brain regions.

Its effects vary widely. Having a CADASIL-associated variant does not mean every person will develop the same symptoms at the same age. MedlinePlus overview

NOTCH3 contains instructions for a receptor protein involved in the function of cells around small arteries. Many CADASIL-causing variants change the number of cysteine building blocks in part of this protein, affecting how it behaves and accumulates around blood vessels. Not every change in NOTCH3 causes CADASIL: the laboratory classification, symptoms and family history all matter. Published NOTCH3 review

CADASIL usually follows an autosomal dominant inheritance pattern. A person with a disease-causing variant has a 50% chance of passing that variant to each child. This is a chance of inheriting the variant, not a prediction of severity. New variants can also occur without a known family history. Genetic counselling can help families discuss testing and reproductive options. GeneReviews

Possible features include migraine with aura, transient ischaemic attacks or strokes, changes in thinking and memory, mood difficulties and reduced motivation. Some people have few symptoms for many years. Symptoms and variation

Assessment brings together symptoms, family history, brain MRI and genetic testing. MRI may show white-matter changes, small deep infarcts called lacunes, or microbleeds, but a scan alone does not confirm CADASIL. A pathogenic or likely pathogenic NOTCH3 variant can establish the genetic diagnosis. A variant of uncertain significance is not confirmation; specialist interpretation and sometimes further investigation are needed. Diagnostic guidance

Care focuses on stroke prevention, symptom management, rehabilitation and support for everyday life. Blood pressure, smoking and other vascular risk factors remain relevant even when the underlying cause is genetic. Migraine, mood difficulties and cognitive problems deserve assessment alongside physical symptoms.

Decisions about antiplatelet medicines or anticoagulation need an individual assessment of potential benefit and bleeding risk, especially where there is another condition requiring treatment. There is no established cure or proven NOTCH3-targeted disease-modifying treatment in routine CADASIL care. European consensus recommendations Treatment research review

Gene therapy aims to change how a gene works or deliver genetic instructions to cells. Modified viral vectors can act as delivery vehicles. Gene editing is a different approach that attempts to alter a DNA sequence. These techniques still require evidence that the right cells can be reached and that the intervention is sufficiently safe and effective. Gene therapy explained

Antisense oligonucleotides, or ASOs, are short synthetic molecules designed to bind a matching RNA sequence. RNA carries and processes instructions from DNA. Depending on their design, ASOs can lower a transcript or change how it is spliced, rather than simply switch a gene off. An ASO does not necessarily edit the underlying DNA. Oligonucleotide mechanisms

Published evidence: Our 2025 NOTCH3 review discusses disease mechanisms and potential therapeutic strategies. It is a review of research, not a clinical trial demonstrating benefit. Our research: CSVD Therapeutics is developing and testing vector and RNA-targeted concepts in experimental systems. Future aim: Build evidence on delivery, safety and disease-relevant effects before any candidate can be considered for patient studies. Read the review Explore therapeutic development.

Observational studies help researchers understand disease progression, genetics, imaging and cognition. Treatment trials answer a separate question: whether an intervention is safe and beneficial. A trial for common lacunar stroke is not automatically suitable for someone with CADASIL.

Read about the UK Familial Cerebral Small Vessel Disease Study and Sheffield's wider contribution on our multicentre research page. ClinicalTrials.gov records provide another route to study information; eligibility and local availability need confirmation with the study team.

Useful questions include: what does my genetic result mean, which symptoms need monitoring, what support is available for relatives, and which studies match my diagnosis? Share a research question with us.