The present invention relates to Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in severe, early-onset axonal neuropathy for p.Arg364Trp Mfn2 mutation in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized with multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type at 7, 40, and 48 weeks showed reduced density of myelinated axons and active axonal degeneration in distal but not proximal nerves, as well as axonal degeneration in the fasciculus gracilis of the cervical spinal cord at 40 and 48 weeks not present in 7-week-old cohort Mfn2 mutants, or wild type at 7 or 40 weeks. The p.His361Tyr Mfn2 mutation using CRISPR/Cas9 showed abnormalities in gait dynamics at 8 weeks and lengthening of gait cycle at 16 weeks. The invention provides progressive axonal neuropathy for examining pathogenesis and treatment of CMT2A.

The present invention relates to: A schizophrenia animal model wherein the model is a mouse in which an anoctamin 1 (ANO1) gene is knocked out in cholinergic neurons of a medial habenula; and a preparation method therefor and the like. The schizophrenia animal model according to the present invention targets the medial habenula which is brain tissue playing a major role in the pathogenesis of schizophrenia, and it has been confirmed that when the ANO1 gene is specifically knocked out in the cholinergic neurons of the medial habenula, positive, negative and cognitive symptoms of schizophrenia are observed, thereby confirming that schizophrenia has been induced. Therefore, the animal model of the present invention is expected to be effectively useful in schizophrenia pathogenesis research and therapeutic agent development and screening.

Aspects of the disclosure relate to methods and compositions for diagnosing and/or treating idiopathic Normal Pressure Hydrocephalus (iNPH). In some embodiments, the methods comprise detecting a level of Cwh43 gene expression or Cwh43 protein in a subject and administering to the subject one or more therapies to treat iNPH based upon the level of the Cwh43 gene expression or Cwh43 protein compared to a control sample.

Method for controlling for the appearance of seizures in the mammalian brain comprising modifying the abundance of a specific miRNA-miR-211, for uses in preventing seizures and providing a model system to examine the effect of a drug or a treatment to seizures.

The disclosed invention relates to methods and transgenic non-human mammals comprising a full length human VIPR2 genomic region integrated into a genome of the mammal. According to a further embodiment the mammal is a mouse. The disclosed invention further relates to transgenic cells from the transgenic non-human mammal. The disclosed invention further relates to therapeutics and methods of treating Schizophrenia in a human comprising administering a therapeutic, where the therapeutic contains one of a pharmacologically effective amount of a hVIPR2 antagonist, and a CRISPR/Cas9 formulation. The disclosed invention further relates to materials and methods of determining efficacy of an antipsychotic therapeutic in treating a condition comprising administering to the transgenic non-human mammal.

The present invention pertains to novel analgesics useful for treating mechanical pain. The invention suggests the use of inhibitors of α-tubulin acetylation for inhibition of neurological sensations that are mediated by sensory neurons. The perception of mechanical pain is can be modulated by altering the α-tubulin acetylation, in context of the invention in particular by modulation of the expression and/or activity of the enzyme α-tubulin acetyltransferase (Atat). The invention provides the medical application of α-tubulin acetyltransferase inhibitors as analgesics and a screening method for the identification of compounds useful in the treatment of pain.

Methods for producing new neurons in the brain in vivo are provided according to aspects of the present invention which include introducing NeuroD1 into a glial cell, particularly into a reactive astrocyte or NG2 cell, thereby “converting” the reactive glial cell to a neuron. Methods of producing a neuronal phenotype in a glial cell are provided according to aspects of the present invention which include expressing exogenous NeuroD1 in the glial cell, wherein expressing exogenous NeuroD1 includes delivering an expression vector, such as a viral expression vector, including a nucleic acid encoding the exogenous NeuroD1 to the glial cell.

The invention is directed to compositions and methods for treating or reducing the likelihood of the development of epilepsy in an individual. The method comprises administering to the central nervous system of an individual in need of such treatment a therapeutically effective amount of an agent capable of increasing the expression and/or activity of miR-128.

Provided herein are methods, compounds, and compositions for reducing expression of sodium voltage-gated channel alpha subunit 2 (SCN2A) in a subject. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a sodium voltage gated channel alpha subunit 1 (SCN1A) related disease or disorder (e.g., Dravet syndrome) in a subject in need.

The present invention relates to the field of seizures. More specifically, the present invention provides compositions and methods for treating refractory seizures in neonates. In one embodiment, the method comprises the steps of (a) administering to the patient an amount of a KCC2 agonist and/or trkB antagonist effective to restore KCC2 expression to normal physiological levels; and (b) administering to the patient an effective amount of an anti-seizure medication.