Neurology 2020: Delivery of nerve growth factor via nasal spray and CNS therapy: State of the art- Founder & President: Maria Rosaria Maglione Foundation Onlus, Italy

Introduction: Antipsychotic drugs are prevalent for the treatment of psychological disorder like schizophrenia. Schizophrenia is a chronic, severe, and hampered brain disorder that has affected people throughout history. It affects how a person thinks, feels and acts and may have difficulty distinguishing between what is real and what is imaginary.The cause of schizophrenia still remains unclear though some researches stated that this disease may be triggered by genetical problem running in families and biological factors like the imbalance in the brain’s chemistry,viral infections and immune disorders. Is there any relation among autism, ADHD, poor learning, stress, depression & mental health? Nerve growth factor (NGF) is the Founding Member of the neurotrophins family of proteins, known for playing a critical protective role in the development and survival of sympathetic, sensory and basal forebrain cholinergic neurons in mammals, including humans. NGF has a neuroprotective action in Alzheimer’s and Parkinson’s disease, as showed by several studies in animal models and humans. NGF can be delivered to the CNS via nasal route and has a neuroprotective action in case of neurodegenerative diseases and brain injury. Furthermore, recent studies have shown an active link between the nasal pathway and the spinal cord in the delivery of NGF to the CNS, thus demonstrating the neuroprotective ability of NGF to support injured neurons in a mouse model of spinal cord injury. Intranasal delivery of NGF has so far been sufficiently investigated in animal models and only recently in humans, as demonstrated in a recent study on long-term intranasal administration of NGF in two patients affected by Frontotemporal Dementia associated with corticobasal syndrome (FTD/CBS) and in another study on intranasal administration of NGF in a Brain Injury. These studies demonstrated the neuroprotective role of NGF administered nasally. Intranasal administration is the most effective and non-invasive way to deliver NGF to the CNS. These neuroprotective properties of NGF make it a strong candidate for the future treatment of neurodegenerative diseases and other pathologies of CNS (brain injury, spinal cord injury, ischemic damage) when administered via nasal route. NGF would not be able to cure the FTD/CBS but these observations support the hypothesis that NGF slows down the usual decline of the disease. However, these studies reinforce the concept that neurotrophins are able to reach and protect the CNS via nasal route and open the way for new lines of research. Hence, these findings suggest the ability of NGF to protect CNS neurons when administered via nasal spray.

Objectives: To assess clinically relevant symptom improvement in patients with major depressive disorder (MDD) receiving vilazodone by using the Montgomery-Asberg Depression Rating Scale (MADRS), a clinician-rated scale used to measure MDD symptom severity and improvement. Method: Pooled data from 2 positive, phase 3, 8-week, double-blind, randomized, placebo-controlled trials in patients with MDD were analyzed. The blood-brain barrier and the blood-cerebrospinal fluid barrier are major obstacles in central nervous system (CNS) drug delivery, since they block most molecules from entering the brain. Alternative drug delivery routes like intraparenchymal or intrathecal are invasive methods with a remaining risk of infections. In contrast, nose-to-brain delivery is a minimally invasive drug administration pathway, which bypasses the blood-brain barrier as the drug is directed from the nasal cavity to the brain. In particular, the skull base located at the roof of the nasal cavity is in close vicinity to the CNS. This area is covered with olfactory mucosa. To design and tailor suitable formulations for nose-to-brain drug delivery, the architecture, structure and physico-chemical characteristics of the mucosa are important criteria. Hence, here we review the state-of-the-art knowledge about the characteristics of the nasal and, in particular, the olfactory mucosa needed for a rational design of intranasal formulations and dosage forms. Also, the information is suitable for the development of systemic or local intranasal drug delivery as well as for intranasal vaccinations. 
If the defect in genes and brain is by nature, scientists can test and detect it to predict autism since the time of pregnancy, infant, but the facts is no, they cannot see any warning until the behaviors, poor skills are obvious! This makes me think problems in genes and brain are just the symptoms in the rainbow of autism. The primary objective of this article is to provide a concise review of the clinical relevance of sleep and vigilance in major depressive disorder. Data Sources: PubMed was reviewed and English-language articles were identified using the key words sleep and depression and sleep and antidepressants. Secondary searches included articles cited in sources identified by the primary search. Study Selection: The narrative review provides brief descriptions of the normal physiology of sleep and changes associated with depression, as well as the impact of various treatments on these processes. Data Synthesis: Although it has long been known that sleep disturbances are an important characteristic of depression, relatively few studies have been conducted with the newer-generation antidepressants. Neither of the most widely used classes of antidepressants, the selective serotonin reuptake inhibitors and the serotonin-norepinephrine reuptake inhibitors, have particularly beneficial effects on sleep and, among the medications that reliably improve sleep efficiency, including mirtazapine and the tricyclic antidepressants, problems with daytime sedation can offset therapeutic benefit. Despite relatively widespread use, trazodone has not been demonstrated to be an effective and safe hypnotic in patients taking other antidepressants. For many patients, ongoing concomitant treatment with benzodiazepines and related drugs is the preferred option, again without convincing empirical support of longer-term efficacy. Among newer and investigational antidepressants, agomelatine shows promise with respect to both overall safety and effects on insomnia, although possible negative effects on liver function warrant further study. Conclusions: Sleep disturbances are a significant aspect of depressive syndromes, and relief of insomnia remains an important unmet need in antidepressant therapeutics. Development of a well-tolerated antidepressant medication that rapidly

Results: The main objective of the study was to investigate the efficacy of chitosan to facilitate brain bioavailability of intranasally administered nerve growth factor (NGF). In vitro permeability studies and electrical resistance studies were carried out across the bovine olfactory epithelium using Franz diffusion cells. The bioavailability of intranasally administered NGF in rat hippocampus was determined by carrying out brain microdialysis in Sprague-Dawley rats. They lack social skills, they cannot talk: language is the product of living environment - as your native language and my native language, we speak it naturally without thinking at all. We are not born with our native language, so I doubt their connection with their living environment and/or the state of mind that they can not/don't want to learn. You can test them with Aesop fables(they do not understand), pretending game - they do not understand, interacting, communicating or persuading.

They are in the low level of this. For official test: you can test them with EQ test, and Aesop stories, metaphors. All these low-level vital skills make them never feel safe, connection to the environment: it makes them stress. Over time, it makes the downward spiral that make them more and more lack of social skills and suffer more stress.

Author(s): Alberto de Bellis

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