The hope of genetic therapy

Ongoing research on ADNP

Here’s a quick, up-to-date snapshot of notable ADNP/ADNP-syndrome research (2024–2025):

• Mechanism & biomarkers

  • ADNP loss alters DNA methylation and mitochondrial gene programs in brain tissue; autopsy work provides new mechanistic clues. BioMed CentralPubMed

  • New work suggests unfolded-protein-response (UPR) activation could serve as a severity biomarker and therapeutic readout in ADNP syndrome. (Transcriptomics, 2025.) Tandfonline

  • Practical lab note: a 2024 study warns that some methods fail to detect truncated mutant ADNP protein in patient cells—important for interpreting assays and trial biomarkers. Nature

  • Sex-dependent biology continues to emerge: ADNP is essential for sex-specific hippocampal neurogenesis pathways. PMC

• Therapeutics (preclinical/clinical-adjacent)

  • Renewed interest in davunetide (NAP/CP201)—the ADNP-derived peptide that stabilizes microtubules—includes a 2025 review of intranasal delivery (brain bioavailability highlighted) and 2024 clinical analyses in other tauopathies supporting mechanism and dosing insights. (Note: ADNP-syndrome trials in children are not yet underway as of Aug 2025.) ScienceDirectNature

  • Background: CP201 holds FDA Orphan Drug designation for ADNP syndrome; prior human experience is from other indications (e.g., PSP, MCI). drugdiscoverytrends.comPMC

  • Academic and foundation groups report work toward targeted genetic/RNA approaches (e.g., at UC Davis’s Interventional Genetics Team), though these remain preclinical. adnpfoundation.org

• Natural history & community science

  • Simons Searchlight released 2024 survey/registry updates and a 2025 spotlight PDF (adaptive behavior, seizure history, and comorbidity tracking)—useful for endpoints and trial design. Simons Searchlightcdn.simonssearchlight.org

  • New case series continue to refine genotype–phenotype links and broaden clinical recognition. (2024–2025 reports.) Wiley Online LibrarySpringerLink

Genetic therapies like CRISPR-Cas9 gene editing or base/prime editing could be used to correct mutations in the ADNP gene. Since ADNP syndrome is usually caused by a single harmful mutation (most often a truncating mutation), correcting or bypassing that error might restore more normal ADNP protein function. This is conceptually similar to approaches being explored for other single-gene disorders such as Duchenne muscular dystrophy or Rett syndrome.

However, there are major challenges for ADNP therapy. The ADNP gene is unusually large and complex, and it regulates many other genes crucial for brain development, making it a “master regulator.” Editing or replacing it safely is technically difficult. In addition, ADNP syndrome affects the brain very early in development, so timing matters — therapies given later in life may only partially help. Delivering gene therapies across the blood–brain barrier is another big hurdle.

That said, research is moving forward. Some teams are studying drug-based therapies (for example, NAP/CP201, a small peptide derived from ADNP itself) to compensate for the gene’s loss of function. Others are investigating whether RNA-based therapies or future gene editing techniques might eventually be able to correct or bypass ADNP mutations. So while gene editing for ADNP syndrome is not currently available in humans, the field of neurogenetic therapy is advancing rapidly, and it’s an area of hope for families and researchers alike.

Some of these researches are further detailed below