$4 Million Research Program Seeks Therapy for ADNP Syndrome

Rare Daily Staff

Researchers at the UC Davis MIND Institute are launching a $4 million three-year program to find transformative therapies for the rare genetic condition ADNP syndrome, funded through a partnership between the ADNP Kids Research Foundation and Simba Global, an international textile company.

ADNP syndrome is a complex neurodevelopmental condition caused by a mutation or change in the ADNP (Activity Dependent Neuroprotective Protein) gene, which affects brain development, connectivity, and function. The syndrome, first identified in 2014, affects males and females in equal numbers. Its core features include delays in development and growth, intellectual disability, and autism or autistic characteristics. It is one of the top single-gene causes of autism.

The impacts of ADNP syndrome can be profound and may include delayed speech, low muscle tone and sensory processing challenges. The brain, heart, and musculoskeletal system are often affected. ADNP syndrome is also associated with distinctive facial features, including a prominent forehead, eyes that are farther apart and droopy eyelids. ADNP syndrome is estimated to affect 1 in 20,000 people in the U.S. and Europe. The incidence is likely higher due to children who’ve gone undiagnosed.

The research will involve the MIND Institute’s interventional genetics team, which includes internationally recognized experts in mouse models for therapeutic development and in gene therapy, including the use of the gene editing tool CRISPR. 

“This is a groundbreaking interdisciplinary project. We are grateful to the ADNP Kids Research Foundation and Simba Global for investing in this research that we hope will have a meaningful impact on the lives of individuals with ADNP syndrome,” said MIND Institute Director Leonard Abbeduto.

The interventional genetics team includes three MIND Institute faculty members who are leading experts in their disciplines: Kyle Fink, assistant professor in the Department of Neurology, the UC Davis Stem Cell Program and the Gene Therapy Center; Jill Silverman, professor in the Department of Psychiatry and Behavioral Sciences and a well-known expert in the use of rodent models for therapeutic development; and David Segal, member of the UC Davis Genome Center and professor in the Departments of Biochemistry and Molecular Medicine and Pharmacology.

The program will include two major phases. First, the team will use stem cell technology to create a human ADNP model in petri dishes. They’ll also characterize mice with ADNP mutations. That will involve looking at cognitive abilities, sleep changes, gait abnormalities and more. Finally, the team will do a deep molecular characterization of the cells in the mice.

“That information will be useful to anyone who wants to study ADNP,” Fink said. “We’ll be able to say, ‘in the mice at this age, there’s this big effect, so if you have a drug, you can test it in this mouse at this age using these tasks.’”

The second phase, the one that “everyone gets the most excited about,” noted Fink, is evaluating therapies for ADNP. To fast-track progress, the team will work simultaneously on three different therapies.

“We think of it as shots on goal,” Fink said. “Time is of the essence with these conditions.”

They’ll be evaluating a traditional gene therapy delivered using a virus, one that has been approved for spinal muscular dystrophy. The team will also assess an ASO (antisense oligonucleotide) that modulates gene expression by binding to mRNA. The third therapy that is being developed uses CRISPR gene editing.

Photo: Leonard Abbeduto, director of the MIND Institute at UC Davis