Two Parents Determination: Sagi and Ella’s Journey to Advance STXBP1 Research

Sagi Gidali and Ella Gordon, parents to Raphael, received the diagnosis of STXBP1 in February 2023 when he was just eighteen months old. Sagi, a cybersecurity entrepreneur, and Ella, a neurologist, call Tel Aviv, Israel, their home. In response to Raphael's diagnosis, they embarked on a journey to seek a cure. Recently, they took a significant step in advancing STXBP1 research by awarding their first grant. Furthermore, Sagi and Ella are establishing a new fund to create a dedicated research arm for STXBP1 in Israel, collaborating closely with the 'Rare Smile' foundation and the best researchers and scientists in Israel. Discover more about their inspiring story and ongoing initiatives in the following blog post.

Sagi, you just gave your first grant for STXBP1 research. Who did you give it to, and what is the research project's goal?

Our first grant is a significant step forward in our fight against STXBP1 disorders. It is awarded to Professor Ilana Gozes from Tel Aviv University, a distinguished researcher at the forefront of neuroscience. The primary goal of this research project is two-fold. Firstly, we aim to establish a R292C mice model, mirroring the specific STXBP1 mutation present in Raphael. His mutation is a recurrent one, but as of now, there is no existing model. It will be crucial for a deeper understanding of the disorder and will also be made available to researchers worldwide, fostering collaborative efforts.

Secondly, we are focusing on testing a drug that prof Gozes developed called NAP (NAPVSIPQ) as a potential therapeutic intervention. NAP, derived from the activity-dependent neuroprotective protein (ADNP), has shown promise in promoting dendritic spine formation and synaptic plasticity. By subjecting Raphael's iPSCs (Induced Pluripotent Stem Cells) to NAP, we intend to observe its impact on the specific mutation associated with STXBP1. The grant aims to contribute valuable tools and insights to the global STXBP1 research community and explore potential avenues for treating this rare disorder.

What was your motivation to give the grant? 

Raphael fills our home with laughter and love. When developmental delays prompted a closer look, Ella and I uncovered the challenging reality of STXBP1 disorders. The diagnosis hit hard, and with zero empathy, the doctor told us the words that we would never forget: ‘There is no cure’. Numerous questions and worries flooded our minds—would he ever speak? Would he walk? What does the future hold? We cried the whole week after, refusing to accept this verdict.

Our motivation is singular and so powerful—Raphael. His laughter and resilience inspire us daily. As parents, Ella and I bring a unique blend of medical expertise and entrepreneurial spirit to the fight against STXBP1. With its wealth of scientific minds, Israel became our starting point for our research arm, and every effort is not just for Raphael but for the entire STXBP1 community.

Rare Smile, the STXBP1 association in Israel, was founded in 2018. How are you working with Rare Smile?

Rare Smile is the Israeli STXBP1 foundation that was founded by Lior and Anat Dor in 2018, after the diagnosis of their son, Ran. Lior and Anat became our guiding light when we needed it most. Armed with a PhD in biology and already driving forward STXBP1 research projects, Lior provided explanations in plain language and opened doors to invaluable connections within the STXBP1 global community.

Our collaboration with Rare Smile is hands-on. Together, we initiated projects like creating IPSCs from Raphael's samples just two weeks after his diagnosis, screening drugs on a C-Elegans (worm) model, and more. Lior and us share a vision for building a robust research arm for STXBP1 in Israel. This partnership goes beyond the scientific; it's about creating a community, leveraging strengths, and transforming Israel into a hub for STXBP1 research. 

What are your overall goals for research in STXBP1?

Our overarching goal is straightforward – finding treatments for STXBP1 disorders and, most importantly, finding a cure. We are exploring drug repurposing projects, examining potential treatments, scouting for new technologies, and collaborating with Israel's best researchers, scientists, and biotech companies. 

Here and now, we initiated an innovative Insilico small molecules scan approach with an Israeli startup named QR Genetics for our drug repurposing project. We found several potential drugs that can stabilize Raphael’s mutation, and we will share the results of our first N of 1 experiment with the entire STXBP1 community in the following months. 

We are delving into futuristic technologies to provide more straightforward and effective solutions for the long term. So, we’ve embarked on a multi-faceted approach to achieve these goals to help Raphael and many other kids and families who are suffering from STXBP1 disorders. 

What challenges have you encountered in your STXBP1 journey, and how are you addressing them?

In our journey, we encountered two main challenges. Firstly, biology and research, by nature, are taking a long time and Raphael is very young, so every minute counts. While we understand the necessity of thorough investigation, we're actively exploring creative avenues to expedite the journey from hypothesis to results, for example, by utilizing AI and cloud computing. The urgency of finding solutions for Raphael propels us to innovate and seek novel ways to shorten these processes without compromising scientific rigor.

Secondly, collaboration is crucial, yet we often face barriers rooted in bureaucracy, intellectual property concerns, and the prevalence of scientists working in silos. The STXBP1 community thrives on shared knowledge, and breaking down these barriers is essential for collective progress. As one example, I’ve been excited to start participating in the STXBP1 Global Connect, a collaborative collective of STXBP1 advocacy groups and country liaisons worldwide. Ella and I are advocating for a culture of open data sharing, emphasizing the need to unite our efforts and expertise to propel STXBP1 research beyond individual silos.

What makes you hopeful about the future for STXBP1?

Hope comes from the evolving landscape of gene therapy and advanced therapeutic approaches. We sense a renaissance, and it feels like a matter of several years until viable solutions emerge. In the interim, we're not sitting idly. Each day is a new challenge but also a step forward. Raphael's progress is a beacon of hope; in these small victories, we find the strength to keep going. The journey is challenging, but the collective efforts of the scientific community, advancements in therapies, and the entire community’s determination paint a hopeful picture for the future of STXBP1.