New Inchstone Project research expands clinical trial possibilities for individuals with ASXL-related disorders

A new paper published by the Inchstone Project marks a turning point in how future clinical trials can better reflect—and include—the most severely affected individuals with developmental and neurogenetic disorders, including ASXL-related disorders.

The study, titled “Caregiver-reported meaningful change in functional domains for individuals with developmental and epileptic encephalopathy: A convergent mixed-methods design”, appears in Developmental Medicine & Child Neurology and represents one of the largest and most comprehensive efforts to understand what “meaningful change” actually looks like for individuals with severe impairments. The research is especially notable for broadening clinical outcome assessment criteria—ensuring that those with profound disabilities are not left out of future treatment research.

ASXL-related disorders were prominently represented in the study, with strong participation from families in our community, thanks in large part to advocacy by ARRE Foundation Board Member Julie Lopez.

“This project is a huge win for our community. Current standardized tests, like the Vineland, don't acknowledge small but meaningful changes - things like head control, or a better way to express pain.  This can lead to a feeling of disconnect even within the special needs community, a lack of study opportunities, and insurance cutting off therapies due to a perceived lack of progress. I'm so grateful to all of those in our community that donated their time to make this a reality.”

The paper provides a framework for measuring small but meaningful functional improvements—such as better grasping, communication of needs, or safer swallowing—that reflect the lived realities of individuals with severe impairments. These kinds of improvements are essential not only for individual well-being, but for daily caregiving, family life, and long-term quality of life.

Dr. Natasha Ludwig, a longtime research partner of the ASXL Rare Research Endowment (ARRE) Foundation and a member of our Medical and Scientific Advisory Board, is among the authors of this paper. Her involvement highlights the alignment between the ASXL research agenda and broader rare disease measurement initiatives.

At the ARRE Foundation, one of our core goals is to ensure future clinical trials are truly inclusive—and that means creating and validating outcome measures that reflect the full spectrum of ability and disability across Bohring-Opitz Syndrome (ASXL1), Shashi-Pena Syndrome (ASXL2), and Bainbridge-Ropers Syndrome (ASXL3). This new research helps move the field forward by laying the groundwork for more equitable and realistic trial design.

To read the full paper, visit: https://onlinelibrary.wiley.com/doi/10.1111/dmcn.16363

We are grateful to every ASXL family who contributed to this important study.