INCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathy

Supplementary Material: The supplementary material is available in the electronic version of this article: https://doi.org/10.3233/JND-210871.Copyright © 2022 The authors. Background X-linked myotubular myopathy (XLMTM) is a life-threatening congenital myopathy that, in most cases, is characterized by profound muscle weakness, respiratory failure, need for mechanical ventilation and gastrostomy feeding, and early death. Objective We aimed to characterize the neuromuscular, respiratory, and extramuscular burden of XLMTM in a prospective, longitudinal study. Methods Thirty-four participants 16 hours/day); 20% required non-invasive support (6–16 hours/day). Median age at tracheostomy was 3.5 months (95% CI: 2.5, 9.0). Thirty-three participants (97%) required gastrostomy. Thirty-one (91%) participants had histories of hepatic disease and/or prospectively experienced related adverse events or laboratory or imaging abnormalities. CHOP INTEND scores ranged from 19–52 (mean: 35.1). Seven participants (21%) could sit unsupported for≥30 seconds (one later lost this ability); none could pull to stand or walk with or without support. These parameters remained static over time across the INCEPTUS cohort. Conclusions INCEPTUS confirmed high medical impact, static respiratory, motor and feeding difficulties, and early death in boys with XLMTM. Hepatobiliary disease was identified as an under-recognized comorbidity. There are currently no approved disease-modifying treatments.The INCEPTUS and ASPIRO studies are sponsored by Astellas Gene Therapies

Primjena i kompozicija individualiziranih zaštitnih elemenata linijske grafike u projektiranju novčanica

Proces stvaranja novčanica je dugotrajan i složen, što rezultira kompleksnim rješenjima koja predstavljaju pravo remek djelo grafike. Novčanice su prožete brojnim detaljima i prenose različite informacije koje se analiziraju u teorijskom dijelu rada. Prvotno se postavljaju kriteriji po kojima se izrađuje detaljna analiza velikog broja zaštitnih i konceptualnih elemenata na primjerima novčanica. Time je prikazan okvirni povijesni pregled razvoja novčanica i utjecaji kojima je bio izložen. Analizira se međuovisnost dizajna o sigurnosnim značajkama, te se ispituje razina informiranosti javnosti o zaštitama na novčanicama. Zaključuje se koje metode zaštite su najučinkovitije, te kako šira javnost najčešće provjerava autentičnost novčanica. U eksperimentalnom dijelu rada se na temelju donesenih zaključaka iz teorijskog dijela izrađuje prototip novčanice koja je u najvećoj mjeri prožeta individualiziranim PostScript programskim rješenjima elemenata linijske grafike (rozete, mikrotekst, zaštitne linije, brojevi apoena), a od ostalih zaštita modeliran je individualizirani raster transformacijom matematičkog izraza u PostScript programski kod. Sve ostale zaštite tipične za novčanice simulirane su alatima za rastersku i vektorsku grafiku. U radu se ispituje utjecaj kompozicije zaštitnih elemenata na prepoznavanje autentičnosti novčanica, te efikasnost samih individualiziranih programskih rješenja

Emerging therapeutic options for sporadic inclusion body myositis

Lindsay N Alfano, Linda P Lowes Nationwide Children’s Hospital, Center for Gene Therapy, Columbus, OH, USA Abstract: Sporadic inclusion body myositis is the most common inflammatory muscle disorder preferentially affecting males over the age of 40 years. Progressive muscle weakness of the finger flexors and quadriceps muscles results in loss of independence with activities of daily living and eventual wheelchair dependence. Initial signs of disease are often overlooked and can lead to mis- or delayed diagnosis. The underlying cause of disease is unknown, and disease progression appears refractory to available treatment options. This review discusses the clinical presentation of inclusion body myositis and the current efforts in diagnosis, and focuses on the current state of research for both nonpharmacological and pharmacological treatment options for this patient group. Keywords: myositis, inclusion body myositis, inflammatory myopathy, treatment, function, outcome