CADASIL

A familial, cerebral arteriopathy mapped to chromosome 19q12, and characterized by the presence of granular deposits in small CEREBRAL ARTERIES producing ischemic STROKE; PSEUDOBULBAR PALSY; and multiple subcortical infarcts (CEREBRAL INFARCTION). CADASIL is an acronym for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. CADASIL differs from BINSWANGER DISEASE by the presence of MIGRAINE WITH AURA and usually by the lack of history of arterial HYPERTENSION. (From Bradley et al, Neurology in Clinical Practice, 2000, p1146)

Also Known As:

Networked: 480 relevant articles (16 outcomes, 67 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	CADASIL
2.	Stroke (Strokes)
3.	Cognitive Dysfunction
4.	Migraine Disorders (Migraine)
5.	Thrombosis (Thrombus)

Experts

1.	Joutel, Anne: 22 articles (01/2022 - 01/2003)
2.	Federico, Antonio: 20 articles (01/2019 - 04/2004)
3.	Dichgans, Martin: 19 articles (01/2022 - 06/2003)
4.	Dotti, Maria Teresa: 18 articles (07/2017 - 04/2004)
5.	Kalimo, Hannu: 17 articles (11/2019 - 07/2002)
6.	Wang, Michael M: 16 articles (03/2022 - 01/2012)
7.	Viitanen, Matti: 16 articles (01/2020 - 07/2002)
8.	Bianchi, Silvia: 16 articles (01/2018 - 04/2004)
9.	Pantoni, Leonardo: 15 articles (06/2021 - 04/2008)
10.	Pescini, Francesca: 13 articles (11/2021 - 04/2008)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to CADASIL:

1.	Stem Cell FactorIBA 01/01/2018 - "Our previous study has demonstrated that repeated treatment with a combination of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) reduces VSMC degeneration and cerebral endothelial cell (EC) damage and improves cognitive function in a mouse model of CADASIL (TgNotch3R90C). " 01/01/2020 - "We have demonstrated the efficacy of treatment with combined stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF) in reducing cerebral small vessel thrombosis in a TgNotch3R90C mouse model of CADASIL. " 01/01/2020 - "Stem Cell Factor in Combination With Granulocyte Colony-Stimulating Factor Protects the Brain From Capillary Thrombosis-Induced Ischemic Neuron Loss in a Mouse Model of CADASIL." 01/01/2018 - "Stem Cell Factor in Combination with Granulocyte Colony-Stimulating Factor reduces Cerebral Capillary Thrombosis in a Mouse Model of CADASIL." 01/01/2014 - "Using both wild type mice and transgenic mice carrying the human mutant Notch3 gene (CADASIL mice), we have recently characterized the pathological features of CADASIL and determined the therapeutic efficacy of two hematopoietic growth factors, stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) in CADASIL. "
2.	Granulocyte Colony-Stimulating Factor (G-CSF)IBA 01/01/2018 - "Our previous study has demonstrated that repeated treatment with a combination of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) reduces VSMC degeneration and cerebral endothelial cell (EC) damage and improves cognitive function in a mouse model of CADASIL (TgNotch3R90C). " 01/01/2020 - "We have demonstrated the efficacy of treatment with combined stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF) in reducing cerebral small vessel thrombosis in a TgNotch3R90C mouse model of CADASIL. " 01/01/2020 - "Stem Cell Factor in Combination With Granulocyte Colony-Stimulating Factor Protects the Brain From Capillary Thrombosis-Induced Ischemic Neuron Loss in a Mouse Model of CADASIL." 01/01/2018 - "Stem Cell Factor in Combination with Granulocyte Colony-Stimulating Factor reduces Cerebral Capillary Thrombosis in a Mouse Model of CADASIL." 01/01/2014 - "Using both wild type mice and transgenic mice carrying the human mutant Notch3 gene (CADASIL mice), we have recently characterized the pathological features of CADASIL and determined the therapeutic efficacy of two hematopoietic growth factors, stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) in CADASIL. "
3.	Proteins (Proteins, Gene)FDA Link 01/01/2000 - "In CADASIL tissues there is a dramatic accumulation of the extracellular domain of the protein which suggests that one of the main mechanisms of CADASIL involves anomalies in the proteolytical cleavage and clearance of this protein. " 11/01/2021 - "CADASIL and CAA protein profiles from recently published proteomics-based and immuno-based studies were compared to investigate the potential for shared disease mechanisms. " 05/01/2007 - "In the present study we used proteomic analysis to characterize the protein expression pattern of a unique material of genetically genuine cultured human CADASIL VSMCs. " 01/01/2023 - "Concentration of non-myocyte proteins in arterial media of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy." 01/01/2023 - "To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey. "
4.	Cholinergic Agents (Cholinergics)IBA 02/01/2008 - "Aim of our study was to test the cortical cholinergic innervation in CADASIL by short latency afferent inhibition (SAI) technique. " 02/01/2008 - "We demonstrated by SAI technique a central cholinergic impairment in CADASIL. " 02/01/2008 - "Motor cortex cholinergic dysfunction in CADASIL: a transcranial magnetic demonstration." 01/01/2007 - "Cholinergic neuronal deficits in CADASIL." 02/01/2008 - "SAI could be used to evaluate the cholinergic dysfunction and potentially the efficacy of cholinomimetic therapy in CADASIL."
5.	Losartan (Cozaar)FDA LinkGeneric 11/01/2023 - "In patients with CADASIL, pairwise comparisons showed that CVR improved with amlodipine compared with atenolol (-39·6 × 10-4%/mm Hg [95% CI -72·5 to -6·6; p=0·019) and with losartan compared with atenolol (-43·3 × 10-4%/mm Hg [-74·3 to -12·3]; p=0·0061). " 11/01/2023 - "Change in CVR did not differ between study drugs in participants with sporadic small vessel disease (mean change in CVR 1·8 × 10-4%/mm Hg [SE 20·1; 95% CI -37·6 to 41·2] for amlodipine; 16·7 × 10-4%/mm Hg [20·0; -22·3 to 55·8] for losartan; -7·1 × 10-4%/mm Hg [19·6; -45·5 to 31·1] for atenolol; poverall=0·39) but did differ in patients with CADASIL (15·7 × 10-4%/mm Hg [SE 27·5; 95% CI -38·3 to 69·7] for amlodipine; 19·4 × 10-4%/mm Hg [27·9; -35·3 to 74·2] for losartan; -23·9 × 10-4%/mm Hg [27·5; -77·7 to 30·0] for atenolol; poverall=0·019). "
6.	Amlodipine (Norvasc)FDA LinkGeneric 11/01/2023 - "In patients with CADASIL, pairwise comparisons showed that CVR improved with amlodipine compared with atenolol (-39·6 × 10-4%/mm Hg [95% CI -72·5 to -6·6; p=0·019) and with losartan compared with atenolol (-43·3 × 10-4%/mm Hg [-74·3 to -12·3]; p=0·0061). " 11/01/2023 - "Change in CVR did not differ between study drugs in participants with sporadic small vessel disease (mean change in CVR 1·8 × 10-4%/mm Hg [SE 20·1; 95% CI -37·6 to 41·2] for amlodipine; 16·7 × 10-4%/mm Hg [20·0; -22·3 to 55·8] for losartan; -7·1 × 10-4%/mm Hg [19·6; -45·5 to 31·1] for atenolol; poverall=0·39) but did differ in patients with CADASIL (15·7 × 10-4%/mm Hg [SE 27·5; 95% CI -38·3 to 69·7] for amlodipine; 19·4 × 10-4%/mm Hg [27·9; -35·3 to 74·2] for losartan; -23·9 × 10-4%/mm Hg [27·5; -77·7 to 30·0] for atenolol; poverall=0·019). "
7.	Atenolol (Tenormin)FDA LinkGeneric 11/01/2023 - "4 weeks of treatment with amlodipine, losartan, or atenolol did not differ in their effects on cerebrovascular reactivity in people with sporadic small vessel disease but did result in differential treatment effects in patients with CADASIL. " 11/01/2023 - "In patients with CADASIL, pairwise comparisons showed that CVR improved with amlodipine compared with atenolol (-39·6 × 10-4%/mm Hg [95% CI -72·5 to -6·6; p=0·019) and with losartan compared with atenolol (-43·3 × 10-4%/mm Hg [-74·3 to -12·3]; p=0·0061). " 11/01/2023 - "Change in CVR did not differ between study drugs in participants with sporadic small vessel disease (mean change in CVR 1·8 × 10-4%/mm Hg [SE 20·1; 95% CI -37·6 to 41·2] for amlodipine; 16·7 × 10-4%/mm Hg [20·0; -22·3 to 55·8] for losartan; -7·1 × 10-4%/mm Hg [19·6; -45·5 to 31·1] for atenolol; poverall=0·39) but did differ in patients with CADASIL (15·7 × 10-4%/mm Hg [SE 27·5; 95% CI -38·3 to 69·7] for amlodipine; 19·4 × 10-4%/mm Hg [27·9; -35·3 to 74·2] for losartan; -23·9 × 10-4%/mm Hg [27·5; -77·7 to 30·0] for atenolol; poverall=0·019). "
8.	CEREIBA 04/01/2013 - "The aim of this study was to evaluate the in vitro protective effects of Cere against oxidative stress-induced apoptosis in cells from CADASIL patients. " 04/01/2013 - "This result showed a protective effect of Cere against oxidative stress-induced apoptosis only in 30 % of the CADASIL patients, suggesting that the Notch3 gene probably does not influence the anti-apoptotic properties of Cere in vitro." 04/01/2013 - "Administration of Cere to PBLs from CADASIL patients cultured under standard conditions had no effect on the percentage of apoptotic cells. "
9.	Acetazolamide (Diamox)FDA LinkGeneric 02/01/2011 - "Assessment of cerebral hemodynamics to acetazolamide using brain perfusion SPECT in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy." 05/15/2010 - "Acetazolamide improves cerebral hemodynamics in CADASIL." 08/01/2000 - "Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking." 06/01/2012 - "Our preliminary experience expands previous reports and confirms the possible efficacy of acetazolamide in CADASIL migraine. " 06/01/2012 - "We retrospectively reviewed our database of patients with a genetic diagnosis of CADASIL to identify how many of them were treated with acetazolamide for the prophylaxis of migraine. "
10.	Lipoprotein(a)IBA 02/01/2012 - "High lipoprotein(a) serum levels in three CADASIL families." 08/01/2010 - "Clinical and genetic features in a family with CADASIL and high lipoprotein (a) values." 08/01/2010 - "We present a family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and elevated lipoprotein(a) [Lp(a)] levels. " 11/01/2004 - "We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. " 01/01/2019 - "Antisense oligonucleotide therapy has shown some promise in treating stroke causes that are genetically determined and resistant to classic prevention approaches such as elevated lipoprotein (a) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). "

Therapies and Procedures

1.	Therapeutics 12/01/2010 - "The pathophysiology of CADASIL is poorly understood, and there is no proven effective therapy. " 01/01/2016 - "There are no therapies for CADASIL and experimental endpoints to examine the preclinical efficacy of potential drugs are lacking. " 01/01/2023 - "In this study, we have developed a novel active immunization therapy specifically targeting CADASIL-like aggregated NOTCH3 ECD. " 01/01/2022 - "Gene testing and imaging studies in symptomatic children with a family history suggestive of CADASIL might aid in early diagnosis, even though there is no effective therapy. " 09/01/2017 - "Further in vivo studies as well as data aggregation and multi-centre controlled clinical trials are needed to confirm the emerging findings in order to identify evidence-based therapies for CADASIL."
2.	Activities of Daily Living (ADL) 01/01/2014 - "After adjustment for age, more CADASIL patients were disabled (impaired on ≥ 2 items of the Instrumental Activities of Daily Living scale) in comparison with ARL patients, and CADASIL patients had worse functional performances evaluated with the Disability Assessment for Dementia (DAD) scale. " 03/01/2014 - "After 21 months of follow-up, deterioration in her cognition and ability to perform instrumental activities of daily living were significant with a follow-up AD8 score of 7. Ascertain Dementia 8 questionnaire is an easy and valid screening tool for early cognitive impairment in patients with CADASIL syndrome." 03/03/2015 - "Current evidence shows that the efficacy on cognitive function and activities of daily living of cholinesterase inhibitors in people with HD, CADASIL, MS, PSP or FTD is unclear, although cholinesterase inhibitors are associated with more gastrointestinal side effects compared with placebo." 03/03/2015 - "However, the treatment effect on other aspects of cognitive change were unclear, measured by the Selective Reminding Test (3 studies, WMD 1.47, 95% CI -0.39 to 3.32, P = 0.12; high quality evidence), patient's self-reported impression of memory change (2 studies, OR 1.67, 95% CI 0.93 to 3.00, P = 0.08; high quality evidence) and cognitive change (1 study, OR 0.95, 95% CI 0.45 to 1.98, P = 0.89; high quality evidence), clinician's impression of memory change (1 study, OR 1.50, 95% CI 0.59 to 3.84, P = 0.39; moderate quality evidence), other psychometric tests, and activities of daily living - patient reported impact of multiple sclerosis activities (1 study, WMD -1.18, 95% CI -3.02 to 0.66, P = 0.21; low quality evidence).One study on patients with CADASIL found a beneficial effect of cholinesterase inhibitors on the Executive interview, and Trail Making Test parts A and B. "
3.	Immunomodulation 01/01/2023 - "Our study has important implications for immunomodulation approaches to counter the characteristic arteriopathy of CADASIL." 10/01/2018 - "If individuals with CADASIL present with immune mediated inflammatory components they may benefit from immunomodulatory therapy. " 10/01/2018 - "Nine cases in the literature of individuals with CADASIL and inflammatory presentations were found with treatment varying from intravenous steroids to MS immunomodulatory therapy. "
4.	Immunotherapy 01/01/2018 - "This study establishes immunotherapy targeting Notch3ECD as a new avenue for disease-modifying treatment in CADASIL that warrants further development. " 01/01/2018 - "Notch3ECD immunotherapy improves cerebrovascular responses in CADASIL mice." 10/01/2013 - "When Aβ (following immunotherapy) and prion protein are released from brain parenchyma they deposit in walls of cerebral capillaries and arteries; GOM in CADASIL accumulates primarily in artery walls. "
5.	Transcranial Magnetic Stimulation 03/01/2013 - "We aimed to study different intracortical circuits and sensorimotor plasticity in CADASIL patients using transcranial magnetic stimulation protocols, and to determine whether these characteristics correlated with the results of clinical neuropsychological evaluation. "