CZI Grant

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In 2022, cureCADASIL and a team of world-renowned researchers were awarded a $1M grant for their collaboration to drive progress for the CADASIL Community as part of the Chan Zuckerberg Initiative’s Patient-Partnered Collaborations for Rare Neurodegenerative Disease (CZI PPC) – a program that supports work by patient communities and scientists to accelerate research in the fight against rare diseases. We’re happy to share that this partnership has successfully received an additional $1M in funding, to be split between research and patient engagement efforts, starting in 2025.

The CZI PPC award supports research centered on science that will close critical knowledge gaps and build a strong foundation for translational efforts, as well as engagement and communications activities to involve and inform the patient community.

CZI PPC-funded Patient Engagement Efforts

Through this partnership, cureCADASIL will receive an additional $200K in funds to help us continue to strengthen patient engagement, drive enhanced educational and communications activities, and support the research team in their effort to make breakthroughs that benefit the CADASIL community.

Last year, we established a Community Advisory Group (CAG) to help guide our community engagement and provide us with feedback and insight on both research and patient advocacy. This year, with integral input from the CAG, we’ve launched a revamped website and logo, and are updating our social media channels. CAG members participated in a Q&A panel moderated by Dr. Elahi at our Patient-Investigator Meeting on June 29 presented the insightful results from the patient survey they created with Dr. Elahi. The results provided the research team with helpful knowledge about the CADASIL community and will help guide their research going forward, so thank you to all who completed the survey. The CAG’s input has been absolutely invaluable in ensuring that our community-geared efforts are reflective of what patients want to see.

Below is the progress made toward our funded milestones:

CZI PPC Patient Engagement Activities Tracker

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 led an insightful discussion about the crucial role of patient participation in research with more than 200 researchers and patient advocates in attendance at the CZI Neuroscience 2024 Meeting. Their discussion was well-received by the research and patient communities alike and emphasized the importance of patient input and involvement in the research process and how cureCADASIL’s CAG has been instrumental in guiding 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 brain 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

Ki Coale

Andria Burroso

Courtney Deplaris

June Wallach

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 in order to 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.

As they wrap up Year 2 of the CZI grant, the Elahi research team is completing their 2024 goals. They have made great progress toward building their 3D in vitro flow models and are now 60% complete working on these models. They’ve also continued to advance their work in analyzing the immune system’s relationship to blood vessels in CADASIL samples; this analysis is 70% complete. A new member has joined the Elahi lab to accelerate progress on this work. Using these recent findings, the researchers are continuing to study 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. The work the Elahi Lab and their collaborators have completed this year will provide the basis for the team’s Year 3 goal: developing a screening tool for drug discovery.

An exciting new avenue the research team started on this year was building miBrain (multicellular integrated brain) models. They have completed creating their first model, but as this is an iterative process, the team is continuing to optimize this model. 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 research team’s first paper from this project is 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.

In other exciting work, Drs. Michael Wang and Fanny Elahi are continuing their collaboration on CADASIL research, with funding from the Department of Veterans Affairs. Their work will 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.

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. We are looking forward to achieving our Year 3 (2025) goals!

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 their 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!

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cureCADASIL Team