A major milestone of the CZI PPC grant is the establishment of a Community Advisory Group (CAG) — a dedicated group of individuals who have knowledge or experience in CADASIL and areas of neurodegenerative disease and stroke who will provide invaluable insights into patient and caregiver perspectives, needs, and aspirations. The CAG has played a vital role in guiding our team toward discovery and providing feedback to cureCADASIL on its patient engagement activities and associated materials. We extend our heartfelt gratitude to all our 2024 CAG members for their participation and thoughtful contributions.

Community Advisory Group

Recently, CAG member Ki Coale and research team lead Dr. Fanny Elahi lead an insightful discussion about the crucial role of patient participation in research with more than 200 researchers in attendance at the CZI Neuroscience 2024 Meeting. Their discussion highlighted the importance of patient input and involvement in the research process and how cureCADASIL’s CAG has helped guide Dr. Elahi’s work. Thank you to all our CAG members for all your hard work!

In addition to our collaborative efforts with patients, we have been working with other researchers and institutions to build a brain donation network. Because donations are a key resource for research like the work Dr. Elahi and her team are completing, we have been working diligently to facilitate the donation of brains to research teams across the country.

Debarag Banerjee, PhD
Community Advisory Group Chair

Ki Coale

Andria Burroso

CZI PPC-funded Research Efforts

The coordinating research PI, Fanny Elahi, MD, PhD, Assistant Professor of Neurology, Neuroscience, and Pathology and Molecular and Cell-Based Medicine at the Icahn School of Medicine at Mount Sinai, received $800K in 2022 to conduct research for 2 years and has received an additional $800K to continue their research through 2026. Dr. Elahi is leading a multi-disciplinary team to build cellular models of CADASIL to reverse engineer the disease and discover new therapeutic targets. They will employ two complementary models of human brain vasculature created from patient samples to understand CADASIL’s early instigating events and disease progression.

Last year, Dr. Elahi and her research team accomplished their Year 1 (2023) goals! They identified proteins that are implicated in CADASIL and discovered that angiogenesis–the renewal and maintenance of blood vessels–is dysregulated in CADASIL patient samples compared to those without the disease. Once they identified this physiological measure of CADASIL, they built in vitro assays–isolated cells of interest–to start determining if this abnormal angiogenesis is a viable target for drug screening.

Now in Year 2 (2024) of their CZI grant, the Elahi research team is building additional models of brain cells, which will enable them to make direct comparisons between cells with and without NOTCH3 mutations and test their predictions. The team is also continuing to advance their work on 3D in vitro flow models and analyzing the immune system’s relationship to blood vessels in CADASIL samples. When combined with their findings in protein analysis and brain cell comparisons, this work will move them toward the next stage of treatment discovery. In the next chapter of this work, they seek to understand how blood vessels and immune cells communicate and the role of abnormal communication in disease progression. This is a complicated question to tackle but given the therapeutic implications it is worth pursuing. This requires larger numbers of patient blood samples to be analyzed (see how you can help below).

New this year, the Elahi team, with help from the Blanchard Lab, has begun building miBrain (multicellular integrated brain) models! In creating each model, the team uses one CADASIL sample, meaning each model represents the brain of an individual participant. The models allow the team to study the pathology of CADASIL by creating access to brain cells at a high resolution outside of the brain. Learnings from these models will generate fundamental knowledge necessary for the development of treatments. The team has tripled in size to work on this aspect of the project and they are aiming to have the first model prototype ready in November. This is a big undertaking and the team’s expectation is to learn by making the first model and then determining what they need to adjust / improve in order make better models. This will be an iterative process, repeatedly improving the model. The donated samples of blood and brain tissue are essential for the team to assess how accurately the models recapitulate brain disease.

Drs. Michael Wang and Fanny Elahi also received new funding to continue their collaboration on CADASIL research. The Department of Veterans Affairs is funding their work to determine core proteins and biochemical pathways that drive the CADASIL disease process. The four-year project promises to unravel how hundreds of different mutations in NOTCH3 result in a single disease.  This work builds upon Dr. Elahi’s on-going CZI study and fundamental biochemical work from the Wang Lab.

The research team is excited to share that the first paper from this project is now available publicly as a pre-reprint and is in peer review. Basic research is going forward and Dr. Elahi and her team are so grateful to everyone who has participated and donated to this work. You can read the full paper on bioRxiv here.

Thank you for continuing to help us push the frontiers of knowledge in CADASIL. This collaborative effort would not be possible without your involvement, so thank you to everyone who plays a role in CADASIL research. Together, we are building the path toward clinical trials and treatments.

Most important to this research and to progress toward treatments are the collaborations between everyone who is touched by CADASIL. New valuable collaborations have been formed through patient connections. CADASIL researchers, industry partners, advocates, and patients have been coming together to solve the questions we all have about CADASIL. This collaborative effort would not be possible without your involvement, so thank you to everyone who plays a role in CADASIL research. Together, we are building the path toward clinical trials and treatments.

Get Involved
In the CZI PPC’s unique funding program, CADASIL patients can participate in research at the bench rather than only in the clinic, making us partners in this truly translational work. Dr. Elahi and cureCADASIL need your help to complete the Year 2 goals and acquire materials to complete the Year 3-4+ milestones. What we need: blood samples and other standard assessments (brief medical exam, brain imaging, and memory tests) from individuals living with CADASIL and from healthy volunteers (family members, friends). We deeply appreciate your consideration and thank everyone who has already volunteered!

Bertram Kasiske
cureCADASIL President

Jane Gunther
(Patient Organization PI)
cureCADASIL Research Director

Pedro De Lencastre
cureCADASIL Secretary

Debra Robinson
cureCADASIL Treasurer

Sandra Talbird
cureCADASIL Trustee

Vinita Bahl
cureCADASIL Trustee

Stellate Communications
Patient Engagement Partner

Fanny Elahi, MD, PhD
(Contact PI) ISMMS

Joel Blanchard, PhD
(co-PI) ISMMS

Towfique Raj, PhD
(co-PI) ISMMS

Shrike Zhang, PhD 
(co-PI) BWH-HMS