It is important to explore various approaches for SMA therapeutics, hence compounds that specifically induce SMNΔ7 read-through, without having prohibitive toxicity, may provide an alternative platform for a combinatorial treatment. Here we established that AZM activity at a low dose can increase SMN protein in disease-relevant animal model and can impact disease severity.

Objective:To evaluate the efficacy, safety, and tolerability of an oral extended-release (ER) formulation of the nonstimulant metadoxine in the treatment of adult attention-deficit/hyperactivity disorder (ADHD).Method: This was a 1:1 randomized, double-blind, placebo-controlled, parallel-design, phase 2 study of metadoxine ER 1,400 mg/d treatment for 6 weeks, following a 2-week baseline/screening period, involving 120 adults with DSM-IV-defined ADHD. A follow-up assessment occurred 2 weeks after the trial was completed. Efficacy measures included changes in Conners' Adult ADHD Rating Scale-Investigator Rated (CAARS-INV) total ADHD symptoms score with adult ADHD prompts (primary measure), response rates (≥ 25% or 40% improvement in CAARS-INV total ADHD symptom score), Test of Variables of Attention (TOVA) performance, and Adult ADHD Quality of Life (AAQoL) total score. The study was conducted from March 15, 2011, to August 21, 2011.Results: Intent-to-treat analysis revealed that subjects receiving metadoxine ER showed statistically significant improvement in CAARS-INV total ADHD symptoms score (P = .02), higher rate of response (≥ 25% [P = .03] or ≥ 40% [P = .04] improvement) on the CAARS-INV total ADHD symptoms score, and improvement in TOVA score (P = .02) and AAQoL score (P = .01) compared with the placebo group. Improvements in ADHD symptoms (scored by CAARS-INV) were significantly different in subjects treated with metadoxine ER versus placebo as early as 2 weeks following treatment initiation. Metadoxine ER was generally well tolerated, with nausea (17% [10/58] Submitted: March 7, 2012; accepted October 4, 2012 (doi:10.4088/JCP.12m07767 A ttention-deficit/hyperactivity disorder (ADHD) is a common and morbid neuropsychiatric condition. Once believed to only affect children, ADHD is now known to persist into adolescence and adulthood in a sizeable number of cases.1-3 Approximately 4%-5% of adults worldwide are affected with ADHD. 4 Adult ADHD is associated with increased health risks and health care costs, higher divorce rates, lower levels of socioeconomic attainment, lower academic achievement, unemployment and workplace deficits, increased risks for motor vehicle accidents, greater likelihood of additional psychiatric disorders, increased criminal activity and incarceration, and higher rates of substance use and abuse. [5][6][7] Most adults with ADHD remain undiagnosed and untreated. 4 While stimulants have been shown to be effective and safe for the treatment of ADHD, a significant percentage of adults with ADHD treated with stimulants either do not respond to or do not tolerate these treatments 8 ; the utility of stimulants is hindered by the potential risk for abuse (stimulants are scheduled drugs 9 ), and the magnitude of effect of nonstimulants in adult ADHD is less than that seen with stimulants.10 Consequently, it is important to develop safe and effective nonstimulant treatment alternatives.MG01CI (hereafter referred to as metadoxine ER) is an extendedrelease oral nonstimulant formulati...

Objectives : Bney Brak city tops Israel’s COVID-19 infection rate and mortality. Before the Jewish New Year (two-day gathering) SARS-CoV-2 PCR positivity rates were 17.6% and reached 28.1% two weeks later Taffix – an innovative nasal powder creates a protective gel over the nasal mucosa blocking viruses from infecting nasal cells, was tested for efficacy in preventing SARS CoV2 infection. Methods : In a prospective users survey, 243 members of an ultra-orthodox community that participated in two days prayers were followed for 14 days following this ‘superspread’ event. Eighty-three used Taffix throughout holiday’s prayers and the following two weeks (ITT). Eighty-one used it regularly (PP). Two used it rarely if at all. The remaining 160 did not use Taffix. Results : After 14 days, 0/81 (0%) of (PP) Tafffix users, 2/83 (2.4%) of (ITT) Taffix users and 16/160 (10%) nonusers were infected. Odds ratio for infection among Taffix users was 0.22, a reduction of 78% (95%CI 1%–95%). No side effects reported. Conclusion : Taffix could be an additional tool against COVID19 spread, in addition to recommended safety measures. This is the first time that a prevention measure of SARS-CoV-2, beyond the use of masks, has proved effective.

Objective To examine the pharmacokinetics and safety of FMXIN001, a new intranasal powder-based naloxone formulation, in comparison to Narcan® nasal liquid spray. Methods FMXIN001, was developed by blending drug microspheres with larger lactose monohydrate particles, that serve as diluent and carrier, as well as a disaggregating agent. Scanning electron microscopy and X-ray were used to characterize the formulation and in vitro deposition was investigated using a nasal cast. We compared the pharmacokinetics and safety of FMXIN001 versus Narcan® in two clinical trials: a pilot study with 14 healthy adults and a pivotal trial in 42 healthy adults (NCT04713709). The studies were open-label, single-dose, randomized, two-period, two-treatment, two-sequence crossover studies to assess the pharmacokinetics and safety of FMXIN001 versus Narcan® nasal spray. Results FMXIN001 comprises naloxone microspheres (5-30 μM) and lactose particles (40–240 μM). Upon in vitro testing, naloxone deposits mainly to the middle turbinates region and the upper part of the nasal cavity of a nasal cast. In human subjects, FMXIN001 produced significantly higher exposure at the initial time points of 4, 10, and 30 min, post-administration, compared to Narcan®. Both treatments were safe and well tolerated. FMXIN001, powder-based spray, results in similar overall exposure to Narcan®, but with more rapid absorption in the first 30 min. Conclusions FMXIN001 is expected to have a shorter onset of action for a more effective therapeutic intervention to manage opioid overdose. Rapid administration of naloxone in cases of opioid overdose is imperative, given the alarming increase in mortality rates.

Introduction: The city of Bney Brak, Israel, (population 210,000 mostly ultra-orthodox Jews) tops Israel list of COVID-19 infection rate and mortality. In mid-September before the Jewish New Year (an intensive two day gathering for prayers) PCR positivity rates were 17.6% and those climbed to 28.1% two weeks later Taffix - is an innovative nasal powder inhaler that creates a protective gel layer over the nasal mucosa and effectively blocks viruses from infecting the nasal cells. Taffix is approved for use in Europe and Israel. In vitro studies demonstrated that Taffix blocks viruses (including SARS- CoV-2) from infecting human cells (<99% ). It is well established that the nose is the main gateway of SARS- CoV-2 to the body. Taffix™ was developed as an additional virus protective tool beyond the currently recommended preventive measures. Methods: In a prospective users survey, 243 members of a Jewish ultra-orthodox synagogue community in Bney Brak that participated in the two days holidays prayers (7 hours spent daily in the synagogue) were followed up for the following 14 days to measure the effect of Taffix in this potentially “super spread” ( post mass gathering) event . 83 collected and used Taffix throughout Rosh Hashana prayers and for the following two weeks (intention to treat group, ITT) . 81 of them used it regularly as instructed ( per protocol, PP) while two used it rarely if at all. The remaining 160 did not use Taffix . Results: At the end of the two weeks follow up - in the ITT population, 2/83 (2.4%) of the Taffix users and 16/160 (10%) of the Taffix non users were infected. The odds ratio for SARS-CoV-2 infection in Taffix users were 0.22 (0.05-0.99, Mid P exact =0.028), a reduction of 78% (95%CI 1%-95%) in odds of infection. No side effects were reported. Conclusion: We suggest that Taffix can be an additional powerful tool against COVID19 spread. To our knowledge this is the first time that any measure to prevent infection in SARS-CoV-2 virus, beyond the use of masks. was proven effective.