Delayed Puberty

Around one in 500 men could be carrying an extra X or Y chromosome -- most of them unaware -- putting them at increased risk of diseases such as type 2 diabetes, atherosclerosis and thrombosis, say researchers. Around one in 500 men could be carrying an extra X or Y chromosome -- most of them unaware -- putting them at increased risk of diseases such as type 2 diabetes, atherosclerosis and thrombosis, say researchers at the universities of Cambridge and Exeter. In a study published in Genetics in Medicine, researchers analysed genetic data collected on over 200,000 UK men aged 40-70 from UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. They found 356 men who carried either an extra X chromosome or an extra Y chromosome. Sex chromosomes determine our biological sex. Men typically have one X and one Y chromosome, while women have two Xs. However, some men also have an extra X or Y chromosome -- XXY or XYY. Without a genetic test, it may not be immediately obvious. Men with extra X chromosomes are sometimes identified during investigations of delayed puberty and infertility; however, most are unaware that they have this condition. Men with an extra Y chromosome tend to be taller as boys and adults, but otherwise they have no distinctive physical features. In today's study, the researchers identified 213 men with an extra X chromosome and 143 men with an extra Y chromosome. As the participants in UK Biobank tend to be 'healthier' than the general population, this suggests that around one in 500 men may carry an extra X or Y chromosome. Only a small minority of these men had a diagnosis of sex chromosome abnormality on their medical records or by self-report: fewer than one in four (23%) men with XXY and only one of the 143 XYY men (0.7%) had a known diagnosis. By linking genetic data to routine health records, the team found that men with XXY have much higher chances of reproductive problems, including a three-fold higher risk of delayed puberty and a four-fold higher risk of being childless. These men also had significantly lower blood concentrations of testosterone, the natural male hormone. Men with XYY appeared to have a normal reproductive function. Men with either XXY or XYY had higher risks of several other health conditions. They were three times more likely to have type 2 diabetes, six times more likely to develop venous thrombosis, three times as likely to experience pulmonary embolism, and four times more likely to suffer from chronic obstructive pulmonary disease (COPD). The researchers say that it isn't clear why an extra chromosome should increase the risk or why the risks were so similar irrespective of which sex chromosome was duplicated. Yajie Zhao, a PhD student at the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, the study's first author, said: "Even though a significant number of men carry an extra sex chromosome, very few of them are likely to be aware of this. This extra chromosome means that they have substantially higher risks of a number of common metabolic, vascular, and respiratory diseases -- diseases that may be preventable." Professor Ken Ong, also from the MRC Epidemiology Unit at Cambridge and joint senior author, added: "Genetic testing can detect chromosomal abnormalities fairly easily, so it might be helpful if XXY and XYY were more widely tested for in men who present to their doctor with a relevant health concern. "We'd need more research to assess whether there is additional value in wider screening for unusual chromosomes in the general population, but this could potentially lead to early interventions to help them avoid the related diseases." Professor Anna Murray, at the University of Exeter, said: "Our study is important because it starts from the genetics and tells us about the potential health impacts of having an extra sex chromosome in an older population, without being biased by only testing men with certain features as has often been done in the past." Previous studies have found that around one in 1,000 females have an additional X chromosome, which can result in delayed language development and accelerated growth until puberty, as well as lower IQ levels compared to their peers. The research was funded by the Medical Research Council.

Statera Biopharma, Inc. (Nasdaq: STAB), a leading biopharmaceutical company creating next-generation immune therapies that focus on immune restoration and homeostasis, today announced submission to the U.S. Food and Drug Administration (FDA) of its Phase 3 clinical trial protocol for STAT-201 in the treatment of pediatric Crohn’s Disease (CD). “Submitting our Phase 3 clinical trial protocol is a critical milestone in our development program,” said Michael K. Handley, President and Chief Executive Officer, Statera Biopharma. “In addition to the common GI symptoms, children with Crohn’s Disease often experience growth failure, malnutrition, delayed puberty, and bone demineralization. STAT-201 has the potential to provide great physical and emotional relief to adolescents who live with Crohn’s Disease.” The Phase 3, multicenter, randomized clinical trial, A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Efficacy and Safety, of STAT-201 in Pediatric Patients Aged 12 to 17 Years (Inclusive) with Active Crohn's Disease, will evaluate the safety and efficacy of STAT-201 compared to placebo in establishing remission in pediatric CD patients. The trial sites are currently being selected and enrollment is expected to launch in early 2022. CD is a chronic relapsing inflammatory condition of the gastrointestinal (digestive) tract, causing symptoms such as persistent diarrhea, abdominal pain, and rectal bleeding. Once considered rare in the pediatric population, it is currently recognized as one of the most important chronic diseases that affect children and adolescents. Approximately 20-30% of all patients with CD present when they are younger than 20 years of age. The signs and symptoms are unpredictable, resulting in physical, emotional, and economic burdens. CD continues to impose significant burdens on patients, despite current treatments, patients continue to have disease flares, smoldering disease, or experience intolerable side effects and new treatment options are needed. STAT-201, Statera’s most advanced drug candidate, is an immune modulator focused on the restoration of mucosal healing and intestinal barrier function as an adjunct to the standard of care in moderate to severe CD. A Phase 2 study demonstrated proof of concept and safety as well as remission in 67% of participants and 43% of true mucosal healing with endoscopies. No serious adverse events were reported in the trial. STAT-201 also has received FDA orphan drug designation for the treatment of CD in pediatric patients. About Statera Biopharma Statera Biopharma (formerly Cytocom, Inc.) is a clinical-stage biopharmaceutical company developing novel immunotherapies targeting autoimmune, neutropenia/anemia, emerging viruses and cancers based on a proprietary platform designed to rebalance the body’s immune system and restore homeostasis. Statera has one of the largest platforms of toll-like receptor (TLR) agonists in the biopharmaceutical industry with TLR4 and TLR9 antagonists, and the TLR5 agonists, Entolimod and GP532. TLRs are a class of protein that plays a key role in the innate immune system. Statera is developing therapies designed to directly elicit within patients a robust and durable response of antigen-specific killer T-cells and antibodies, thereby activating essential immune defenses against autoimmune, inflammatory, infectious diseases, and cancers. Statera has clinical or preclinical programs for Crohn’s disease (STAT-201), hematology (Entolimod), pancreatic cancer (STAT-401) and COVID-19 (STAT-205) in addition to potential expansion into fibromyalgia and multiple sclerosis.