CADASIL

This study is a single-center, prospective, single-arm, self-controlled clinical trial designed to assess the safety and efficacy of edaravone dexborneol sublingual tablets for blood-brain barrier (BBB) dysfunction in patients with CADASIL. The study will enroll approximately 60 participants aged 18 to 80 years with genetically confirmed CADASIL. Participants will be followed for a total duration of 12 months, including two consecutive phases. * Phase 1 is a 6-month natural history observation period, during which participants do not receive the study drug and continue their routine standard care for CADASIL. * Phase 2 is a 6-month drug intervention period, in which participants will receive edaravone dexborneol sublingual tablets to investigate the effect on the BBB water exchange rate (kw), measured by diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI, and to assess potential benefits on stroke risk reduction, cognitive function, and gait performance. The primary endpoint is the change in kw measured by DP-pCASL. Secondary endpoints include the incidence of clinical stroke events; changes in neuropsychological performance, MRI-based CSVD biomarkers, gait and motor assessments, functional disability and activities-of-daily-living scales, and peripheral blood biomarkers. Safety assessments will include adverse events (AEs) and serious adverse events (SAEs).

This is a human clinical study involving the isolation of autologous bone marrow derived stem cells (BMSC) and transfer to the vascular system and inferior 1/3 of the nasal passages in order to determine if such a treatment will provide improvement in neurologic function for patients with certain neurologic conditions. http://mdstemcells.com/nest/

CERVCO is the French National Reference Centre for Rare Cerebrovascular and Retinal Diseases, accredited by the Ministry of Health since 2005. Since 2017, CERVCO has coordinated the MRVC cohort, a prospective cohort of patients with rare vascular diseases of the brain and retina, and established the associated B-MRVC biobank in 2020 to support translational research and biomarker discovery. Due to the rarity and heterogeneity of these disorders, centralized longitudinal collection of clinical data and biological samples is essential to improve understanding of disease mechanisms, identify biomarkers of progression and prognosis, and facilitate the development of new diagnostic and therapeutic approaches. The present study aims to expand this longitudinal biobank, enable national and international collaborative research through controlled sample sharing, and establish reference control samples to support biomarker validation.

K-CADASIL is a 10-year prospective study of 500 Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic brain disease that causes stroke and dementia. The investigators will track symptoms, brain scans, memory tests, and gene information to understand disease progression in Koreans and identify better treatments. Participants will visit clinics regularly for check-ups and blood tests. This study aims to help improve care for CADASIL patients and families worldwide.

Cerebrovascular diseases (CVDs) are one leading cause of morbidity and mortality worldwide. Despite intensive investigations, more than 30% of strokes remain of undetermined origin. Rare Cerebrovascular Diseases (rCVDs), including heritable (i.e., CADASIL, COL4A1 syndrome, Fabry disease) and acquired conditions (i.e., Sneddon syndrome, Moyamoya arteriopathy) account for a proportion of these strokes. However, rCVDs are often misdiagnosed since clinicians are not able to recognize them. Although rare, the identification of these stroke causes is important to establish appropriate management measures, including genetic counselling, and, if available, therapy. The lack of data on phenotype and clinical course of rCVDs, given the paucity of published series, makes the diagnosis and the development of therapies challenging. Furthermore, the molecular characterization of rCVDs is still lacking, despite progresses achieved in common stroke by applying high throughput approaches as multi-omics. Since the diagnosis and care of rCVDs require adequate expertise and instrumental tools, clinical and research activities are usually reserved to few specialized centers, mostly located in the North of Italy, leading patients to expensive trips for consultations. Therefore, the creation of a clinical and research network aimed at improving the diagnostic pathways of rCVDs is highly needed to improve the number of patients with rCVDs to better define the clinical phenotype and to transfer the knowledge on rCVDs in other centers overall Italy filling the geographical gap affecting Southern Italy.

The TAG-SVD enrolled patients with clinical and neuroimaging features of cerebral small vessel disease (CSVD). All enrolled patients will receive next-generation sequence (NGS) with probes designed to target five candidate CSVD genes, and patients will be divided into genetic or non-genetic groups accordingly. Their clinical features and outcome will be followed for at least 2 years.

This is an observational study to better understand the risk factors and progression of CADASIL, a leading cause of vascular cognitive impairment and dementia (VCID). 575 participants will be enrolled and can expect to be on study for up to 5 years.

The Myelin Disorders Biorepository Project (MDBP) seeks to collect and analyze clinical data and biological samples from leukodystrophy patients worldwide to support ongoing and future research projects. The MDBP is one of the world's largest leukodystrophy biorepositories, having enrolled nearly 2,000 affected individuals since it was launched over a decade ago. Researchers working in the biorepository hope to use these materials to uncover new genetic etiologies for various leukodystrophies, develop biomarkers for use in future clinical trials, and better understand the natural history of these disorders. The knowledge gained from these efforts may help improve the diagnostic tools and treatment options available to patients in the future.

The project aims to retrospectively and prospectively analyze a population of CADASIL patients in order to study the natural history of the disease by correlating the symptom spectrum with genetic risk and specific neuroradiological and biological markers \- Stratifying patients according to their disease risk, this could contribute to the discovery of personalized therapeutic targets.

Cerebral small vessel diseases (cSVD) are diseases of brain tissue involving vessels (arterioles or capillaries) with a diameter of less than 400 microns. Within this group, CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is the most common familial form. CADASIL is due to mutations in the NOTCH3 gene located on chromosome 19. It is considered a unique model for the study of cSVD. CADASIL begins between the ages of 20 and 40, with the appearance of cerebral white matter hyper-signals visible on MRI. Before the age of 30, patients are usually asymptomatic. To date, there are no available treatments. To test new therapeutic approaches, we need biomarkers that are robust and sensitive enough to assess the effects of these treatments at an early stage of cSVD and over a relatively short period of time. An ideal monitoring biomarker should be repeatedly and safely usable, easily accessible, accurate, reproducible and sensitive to disease progression or pharmacological intervention. Alterations in neurovascular coupling (NVC) have been recognized as one of the earliest functional alterations occurring during cSVD. Cerebral functional magnetic resonance imaging (fMRI) is a brain imaging technique that measures the activity of brain areas in vivo by detecting local changes in blood flow. An important advantage of blood oxygen level-dependent functional MRI is that it enables the NVC to be probed in vivo, safely and repeatedly in humans. Our central hypothesis is that functional MRI can provide such a biomarker for monitoring CNV disease progression in vivo using a dedicated fMRI protocol that can be used on a clinical MRI scanner, is reproducible and varies according to the severity of brain MRI lesions and/or clinical manifestations in CADASIL. A functional imaging study coupled with electroencephalogram has already revealed changes in the hemodynamic response to visual or motor stimuli in patients at the early stage of the disease. This study is exploring new imaging protocols to focus on the purest vascular response.

The aim of this project is to establish an Australian cohort of patients diagnosed with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). This study will examine the clinical features and longitudinal course of CADASIL. Outcome measures include neuropsychological profile, neuroimaging, genetics, blood biomarkers, and retinal imaging.

The aim of this study is to determine the clinical spectrum and natural progression of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and related disorders in a prospective multicenter study, to assess the clinical, genetic and epigenetic features of patients with CADASIL , to optimize clinical management.

Prognosis of small vessel disease (SVD) depends on the underlying type of SVD and index manifestation. The aim of this prospective, observational cohort study is to determine the risk of different outcome events among patients with SVD according to the type of index presentation.