Abstract
Activity-dependent neuroprotective protein (ADNP) syndrome, also known as Helsmoortel-Van Der Aa syndrome, is a rare condition, which is diagnosed in children exhibiting signs of autism. Specifically, the disease is suspected when a child is suffering from developmental delay and/or intellectual disability. The syndrome occurs when one of the two copies of the ADNP gene carries a pathogenic sequence variant, mostly a de novo mutation resulting in loss of normal functions. Original data showed that Adnp+/− mice suffer from learning and memory deficiencies, muscle weakness, and communication problems. Further studies showed that the ADNP microtubule-interacting fragment NAP (called here CP201) resolves, in part, Adnp deficiencies and protects against ADNP pathogenic sequence variant abnormalities. With a clean toxicology and positive human adult experience, CP201 is planned for future clinical trials in the ADNP syndrome.
Highlights
The Activity-dependent neuroprotective protein (ADNP) syndrome traits include limitations of social interactions and communication along with stereotypic, repetitive behavior, and restricted interest (1)
We have previously shown that CP201 enhanced the interaction of the intact ADNP with MT-Tau (6, 37)
Treating the ADNP-mutated cells with CP201 protected against ADNP mutation-induced MT dysfunction (24, 25). These results suggest that CP201-induces increased interaction of the intact ADNP with MT-Tau (6) and provides cellular protection (37), in the face of ADNP pathogenic sequence variants (25)
Summary
The ADNP syndrome (https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=404448; https://rarediseases.info.nih.gov/diseases/12931/adnp-syndrome) traits include limitations of social interactions and communication along with stereotypic, repetitive behavior, and restricted interest (1). Heterozygous mutations of Adnp (Adnp+/−) result in Tau (MT associated protein) hyperphosphorylation paralleled by cognitive deficits. ADNP/CP201 dramatically increase microtubule end-binding protein-Tau interaction: a novel avenue for protection against tauopathy (6) even in the face of multiple ADNP mutations (24, 25)
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