The challenge: Moving beyond “admiring” the problem

In pediatric rare disease research, the primary roadblock is often the “silo” effect. Clinicians, engineers, and families frequently work in isolation, resulting in fragmented data and trials that fail to capture the nuances of a child’s daily life.

For STXBP1, a rare neurodevelopmental disorder, the lack of validated biomarkers has stalled drug development. While tremors and motor instability are hallmark symptoms, traditional clinical visits are too brief to capture these fluctuating patterns.

This Deep Dive explores how Rafa’s Moonshot and ActivInsights  are leveraging DiMe’s Core Measures for Pediatric Rare Disease framework to transform real-world motor symptoms into quantifiable, regulatory-ready digital biomarkers. Read on to hear from DiMe’s Lucy Cesnakova, program lead, as she learns more from Rafa’s Moonshot Founder, Sagi Gidali, and ActivInsights  CTO, Joss Langford.

The partners

• Rafa’s Moonshot: A patient-led organization advancing therapies for STXBP1, a rare neurodevelopmental disorder caused by mutations in the STXBP1 gene, which plays a critical role in brain development. Rafa’s Moonshot was founded by a tech entrepreneur and a neurologist for their son, Raphael, and hundreds of children with STXBP1 worldwide. They bring execution speed and clinical depth to accelerate therapies for STXBP1.
• ActivInsights : A global leader in professional-grade wearables and data analytics, specializing in capturing high-resolution, sensor-level data that reflects the reality of patient life. For the STXBP1 study, their GENEActiv wearable is being used to capture objective motor function data.

Lucy (DiMe): Rare disease drug development is often hamstrung by silos. How did your partnership break that mold, and what specific gap were you closing?

Sagi: STXBP1 development lacks validated biomarkers. We knew tremors were clinically relevant, but only if measured objectively. We initially approached ActivInsights  for technical advice, but their genuine commitment to the patient experience turned a consultation into a true partnership. We saw an opportunity to translate “home-life” symptoms into quantifiable biomarkers.

Joss: We recognized that the challenges in STXBP1 mirrored other complex populations. In rare disease, resources are limited; a cross-functional approach isn’t just “nice to have”—it’s the only way to truly understand the lived experience.

Lucy: Why weren’t “generic” wearables enough to capture the needs of children with STXBP1?

Sagi: Motor instability fluctuates. It’s hard to capture in a 20-minute clinic visit, but it’s devastatingly obvious when a child tries to eat at home. Generic trackers aren’t designed for that level of specificity.

Joss: To see a tremor, you need high-resolution, raw sensor data recorded continuously for days. This requires specialized, low-burden wearables. We also insist on open data formats and algorithms—not the “black box” approach of consumer tech—so we can contribute findings back to the global scientific community.

Lucy: You’re launching a pilot study on a small molecule. How do you ensure the “numbers” you collect reflect meaningful changes in a child’s life?

Sagi: Because STXBP1 is highly heterogeneous, we focus on “within-patient” changes, comparing each child to their own baseline. We integrate motor data with caregiver reports and seizure frequency to ensure no signal is interpreted in isolation.

Joss: We characterize the frequency and intensity of behavioral bouts to build a picture families can relate to. This creates a dialogue: we focus on what is both measurable and relevant to the people living with the disease.

Lucy: This study aligns with DiMe’s framework of ‘Core digital measures for pediatric rare diseases’. Why is it important for even a small, single-arm exploratory trial to use a standardized framework?

Sagi: Today, seizure frequency is often the only measure used, but it’s “noisy” and doesn’t apply to all children. Establishing a continuous, objective way to measure movement is transformative. Using a standardized framework also ensures we are aligned with regulatory expectations, like the FDA, from day one.

Joss: It ensures we are “talking the same language.” Our collaboration helped inform the development of these core measures; now, the framework helps us communicate clearly with regulators and global research initiatives.

Lucy: What is your key takeaway for other parent-led organizations and researchers?

Sagi: Don’t wait for a top-down solution. When families, clinicians, and tech partners work as equals, you move faster and ask better questions. Define the problem clearly and build collaborations around shared ownership of the impact.

Joss: Listen. As developers, it is our responsibility to translate sensor data into relatable concepts. Digital measures can shine a light where traditional techniques struggle to see.

More about the participants:

• Sagi Gidali (Rafa’s Moonshot): Founder and tech entrepreneur channeling parental urgency into measurable, real-world improvements for children like his son, Raphael.
• Joss Langford (ActivInsights ): CTO and measurement scientist specializing in translating raw data into clinical insights optimized for specific disease populations.
• Lucy Cesnakova (DiMe): Program Lead at DiMe, specializing in turning multi-stakeholder expertise into actionable tools for digital clinical measurement.

Bring these measures to your research: Explore the full toolkit for Core Digital Measures for Pediatric Rare Diseases and learn how you can use these standardized domains to accelerate your own trials.