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cureCADASIL Association

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cureCADASIL Association Announces Publication of Dr. Arboleda-Velasquez’s Study Showing Promising Results of Notch3 Antibody in a Mouse Model of CADASIL

Plainsboro, NJ, July 15, 2017 --( cureCADASIL, a Plainsboro, NJ non-profit focused on funding research and raising awareness for the rare, genetic disorder cerebral autosomal dominant arteriopathy with subcortical infarcts (CADASIL) continued support of preclinical CADASIL research by Dr. Joseph Arboleda-Velasquez from Schepens Eye Research Institute of Mass Eye and Ear, and Harvard Medical School came to fruition in a study published July 11 in the Journal of Experimental Medicine. CADASIL is a disorder of the small blood vessels that causes subcortical transient ischemic attacks or strokes, and progresses to early vascular dementia. Though rare, this genetic form of stroke is the most common cause of vascular dementia and is inherited with a 50 percent chance by family members.

This study showed that an activating antibody directed against Notch3 reduced mural cell loss, a hallmark characteristic of CADASIL. Although still in mice, this suggests that activating Notch3 antibodies could be developed as therapeutics to reduce disease progression in CADASIL patients. Importantly, this treatment significantly increased plasma proteins previously reported by Dr. Arboleda’s laboratory (Primo et al., 2016) as associated with Notch3 activity. Plasma levels of Notch3, therefore, could be a potential biomarker for this or other Notch3 regulating molecules.

Dr. Arboleda’s team studied the importance of mural cells in vascular integrity and mural cell loss, a known characteristic of CADASIL and other small vessel diseases, in Notch3 knockout mice. CADASIL is a single gene disorder caused by mutations on the Notch 3 gene. This study showed that treatment with an agonist Notch3 antibody prevented mural cell loss in mice with the C455R mutation, a CADASIL mutation associated with Notch3 loss of function. These results open the possibility for treatment of CADASIL in humans by preventing loss of Notch3 signaling.

“We are excited to see Dr. Joe's work published and proud to have supported his CADASIL research over the past 5 years,” said Nancy Maurer, President of cureCADASIL. “We are grateful for the families and other donors who helped fund this important research to date and continue to support CADASIL research priorities.”

cureCADASIL has supported Dr. Arboleda’s research focused on identifying CADASIL biomarkers, necessary for future clinical trials in humans, which resulted in a 2016 publication (Primo et al., 2016). cureCADASIL has also provided funding for Dr. Arboleda’s current research for a treatment for the rare, neurodegenerative small vessel disease (Machuca-Parra et al., 2017). Dr. Arboleda, a member of the cureCADASIL Scientific Advisory Board since its inception in 2012, has received funding through both cureCADASIL’s summer scholarship program and Research Alliance program, aimed at providing bi-annual funding to help accelerate CADASIL research and publication.

To help fund this and other important CADASIL research, please donate to cureCADASIL.

“Dr. Arboleda-Velasquez’s results are exciting developments for the CADASIL field,” said Dr. Irene Griswold-Prenner, SAB member of cureCADASIL. “If these results translate from mouse models to humans, they provide an avenue to approach treatment for CADASIL patients. Importantly they also point to a target engagement biomarker to support CADASIL clinical trial development. Since no treatments currently exist for CADASIL patients, this is a significant advance for CADASIL research.”

There are no current treatments for CADASIL; however other potential treatments are in preclinical development. Research by Dr. Arboleda and others, including Dr. Li-Ru Zhao of SUNY Upstate, will be presented in an upcoming online webinar series to be hosted by cureCADASIL to facilitate discussions among CADASIL researchers, physicians, and patients. For more information, please contact

About cureCADASIL Association
cureCADASIL Association is a non-profit 501(c)(3) organization run by an all-volunteer Board of Trustees. We are dedicated to families whose lives are touched by CADASIL. The mission of cureCADASIL Association is to raise awareness of CADASIL, ensuring it will be universally recognized and understood by the medical community, enabling patients to be correctly diagnosed and ultimately treated. For more information please visit, join the CADASIL Family Registry at and follow us on Facebook, Twitter, and YouTube.

Nancy Maurer
cureCADASIL Association
10 Schalks Crossing Road
Suite 501-A-133
Plainsboro, NJ 08536
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cureCADASIL Association
Sandra Talbird

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