naphthoquinones and Syndrome

Previous findings showed that in mice, complete knockout of activity-dependent neuroprotective protein (ADNP) abolishes brain formation, while haploinsufficiency (Adnp+/-) causes cognitive impairments. We hypothesized that mutations in ADNP lead to a developmental/autistic syndrome in children. Indeed, recent phenotypic characterization of children harboring ADNP mutations (ADNP syndrome children) revealed global developmental delays and intellectual disabilities, including speech and motor dysfunctions. Mechanistically, ADNP includes a SIP motif embedded in the ADNP-derived snippet drug candidate NAP (NAPVSIPQ, also known as CP201), which binds to microtubule end-binding protein 3, essential for dendritic spine formation. Here, we established a unique neuronal membrane-tagged, GFP-expressing Adnp+/- mouse line allowing in vivo synaptic pathology quantification. We discovered that Adnp deficiency reduced dendritic spine density and altered synaptic gene expression, both of which were partly ameliorated by NAP treatment. Adnp+/-mice further exhibited global developmental delays, vocalization impediments, gait and motor dysfunctions, and social and object memory impairments, all of which were partially reversed by daily NAP administration (systemic/nasal). In conclusion, we have connected ADNP-related synaptic pathology to developmental and behavioral outcomes, establishing NAP in vivo target engagement and identifying potential biomarkers. Together, these studies pave a path toward the clinical development of NAP (CP201) for the treatment of ADNP syndrome.

Topics: Amino Acid Motifs; Animals; Autistic Disorder; Behavior, Animal; Biomarkers; Cell Membrane; Dendritic Spines; Gene Expression Regulation; Homeodomain Proteins; Humans; Mice; Mice, Knockout; Microtubules; Models, Neurological; Mutation; Naphthoquinones; Nerve Tissue Proteins; Synapses; Syndrome

Topics: Azo Compounds; Dermatitis, Allergic Contact; Dermatitis, Occupational; Female; Hair Dyes; Humans; Middle Aged; Naphthoquinones; Quaternary Ammonium Compounds; Syndrome; Urticaria

Capecitabine is a chemotherapeutic drug for use in cancers. Hand-foot syndrome (HFS) is side effect of capecitabine which can lead the cessation of the therapy or dose reduction. Henna (Lawsonia inermis) is a traditionally used plant of Middle-East that is applied on hands and feet. Some of cancer patients in capecitabine treatment who developed HFS, we recommended to apply henna. In these patients, six patients were grade 3 HFS and four were grade 2 HFS. Complete response (CR) were seen in four of grade 3 HFS and all of grade 2; two grade 3 HFS improved to grade 1. So far, in the chemotherapy, there was no need of dose reduction and also no side effect of henna seen. Clinical improvement in these patients may relate to anti-inflammatory, antipyretic and analgesic effects of henna. Prospective studies are needed to show this therapeutic effect of henna.

Topics: Administration, Cutaneous; Adult; Aged; Antimetabolites, Antineoplastic; Capecitabine; Deoxycytidine; Female; Fluorouracil; Foot Dermatoses; Hand Dermatoses; Humans; Middle Aged; Naphthoquinones; Neoplasms; Paresthesia; Severity of Illness Index; Syndrome; Treatment Outcome