BIOMEDICA CRO’s Post

At BIOMEDICA CRO, we consistently participate in projects that require the collection of #biospecimens🩸 from subjects with #AlzheimersDisease and other neurological conditions. Moreover, our extensive network of hospitals allows us to join new projects as well. I am proud to have the opportunity to contribute to the research in collaboration with the best Colleagues and Customers ever!💫 #Research #Diagnostics #Neurology #PrecisionMedicine #Biotech

Here are some fascinating insights into sudden unexpected death in epilepsy (SUDEP), sudden cardiac death (SCD), and sudden arrhythmic death syndrome (SADS), from our Medical Director Ley Sander. 💜

People with epilepsy can die suddenly. There are three leading causes: sudden unexpected death in epilepsy (SUDEP), sudden cardiac death (SCD), and sudden arrhythmic death syndrome (SADS). These are related to each other, but they are not precisely the same.  In this article, we looked at the number of people who die from these causes, what might cause them, and how they happen. We also reviewed what other researchers have said about sudden death in epilepsy. It is essential to know if an autopsy was done and what the physician thinks caused the death. The definitions of SUDEP, SCD, and SADS can significantly overlap. Seizures can sometimes cause heart problems, but this is not the main reason for SUDEP. People with epilepsy are more likely to die suddenly if they also have heart problems. Genetic factors may be involved in all three conditions, but it is not always clear if they cause the issues or are just there by chance. To figure out if someone with epilepsy is at risk of sudden death, we need to look at their medical history, do tests, and do a complete post-mortem. If someone with epilepsy dies suddenly, doctors should consider testing their family members for genetic problems. More work is needed to understand better the differences between SUDEP, SCD, and SADS, as well as to develop ways to predict who is at risk and how to prevent sudden death. Epilepsy Society UCL SEIN - Expertisecentrum voor epilepsie en slaapgeneeskunde SUDEP Action https://lnkd.in/etJd_-YC

Overlooked Neurological Features Present in Long COVID By Svetlana Blitshteyn, MD, FAAN "For many years, those of us who specialize in these disorders have seen patients with very similar features that the patients with Long COVID have. Many of them presented [these features] after some viral or bacterial infection." Following the infection rise from the COVID-19 pandemic, neurologists have diverted attention into trying to understand how their patients can manage the long-term symptoms of this infectious disease. Those previously infected have increasingly reported experiencing symptoms of Long COVID, also known as post-acute COVID, which can last for weeks or more following mild illness. This emerging condition may be related to a virus- or immune-mediated disruption of the autonomic nervous system that can cause orthostatic intolerance syndromes.1 As this issue continues to be a prevalent trend, it may be important for neurologists to able to recognize these cases among their patients in order to provide better support toward the management of their condition. Dysautonomia, often identified by autonomic nervous system dysfunction, includes a variety of disorders with the most frequent reported cases being postural orthostatic tachycardia syndrome, neurocardiogenic syncope, and orthostatic hypotension.2 In a recent literature review published in Current Neurology and Neuroscience Reports, studies showed a significant overlap and shared pathophysiology in migraine and dysautonomia disorders. Author Svetlana Blitshteyn, MD, FAAN, director and founder of Dysautonomia Clinic, noted in the review that diagnosis and treatment of these disorders among those with migraine is crucial for providing patient centered care, reducing symptom burden, and improving functional impairment. In a recent conversation with NeurologyLive®, Blitshteyn, who also serves as a clinical associate professor of neurology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences, discussed how the neurological symptoms associated with COVID-19 have shed light on previously neglected post-viral manifestations. She also talked about the initiatives neurologists can undertake to bridge the gap between established medical practices and evolving scientific understanding. In addition, Blitshteyn spoke about the implications of recognizing and addressing neurological manifestations of systemic diseases, such as migraine. Posted by Larry Cole

Excited to share a recent publication in Pediatric Neurology from my time at Boston Children's Hospital: "Inaugural Patient-Reported Registry of Pediatric Opsoclonus-Myoclonus-Ataxia Syndrome: Presentation, Diagnosis, and Treatment of 194 Patients." This paper represents a novelty in rare disease research, utilizing entirely patient-reported data to yield insight into OMAS, one of several devastating pediatric #neuroinflammatory conditions our team regularly treated. One year out, I'll forever be grateful to have contributed to this important work. 📄 https://lnkd.in/ejwg9WPP #OMSLife #OMAS OMSLIFE FOUNDATION INC #opsoclonus #raredisease #neurology #psychiatry #neuroimmunology #neuroscience #iamrare

A new therapeutic target offers a promising pathway for multiple sclerosis treatment #Researchers from #Kyushu University have identified a potential therapeutic target for the treatment of advanced multiple #sclerosis (MS), a potentially disabling condition associated with the central nervous system. In their latest study, conducted using an experimental mouse model of MS, they explored the role of connexin 43 (Cx43), a protein involved in cellular communication and cardiac function, and examined whether targeting this protein with specific blockers could improve MS symptoms. Like most neurodegenerative diseases, MS has very limited treatment options, more so once it reaches the chronic stage. To add to this, MS affects nearly three million people worldwide, making it a massively challenging #neurological disease. Though our understanding of the precise nature of MS is limited, researchers have established that MS is caused by the patient’s own immune system wreaking havoc on their central nervous system. Specifically, the immune system attacks the protective myelin sheath surrounding nerve fibers in the brain and spinal cord, causing demyelination and creating areas of scarring and damage called lesions. In a 2013 study, researchers from Kyushu University, including Associate Professor Ryo Yamasaki from the Faculty of Medical Sciences, found that the production of Cx43 was increased in supportive cells called astroglia, near chronic MS lesions. As mentioned earlier, Cx43 is essential for cell-to-cell signaling and plays a key role in modulating the immune system. The researchers therefore hypothesized that Cx43 could play a pivotal role in promoting neuroinflammation - a process where the immune response is triggered to fight off infection or heal damaged tissue - in the context of MS, ultimately leading to demyelination. Now, a recent study published in Scientific Reports on May 13, 2024, by Yamasaki, in collaboration with researchers from the International University of Health and Welfare, adds further support to the hypothesis that Cx43 plays a key role in causing MS. Their study has revealed that a drug called INI-0602, which effectively ‘plugs’ and blocks Cx43 channels, markedly improved MS symptoms in experimental mice. The researchers conducted an extensive series of experiments in an experimental mouse model of MS and in cultured astroglia cells from the mouse model, to understand the effects of Cx43 blockade. The results of these tests and analyses were quite consistent, suggesting that INI-0602 could not only suppress the overproduction of Cx43 in astroglia, but also mitigate many of the hallmark features of MS, including demyelination and excessive immune cell infiltration into the nervous system. By delving further into the mechanisms underlying these results, the team found that INI-0602 led to improved symptoms by regulating immune processes.

This study shows the delivery of antisense oligonucleotide (#ASO) against UBE3A-AS transcript (involved in Angelman syndrome - a neurodevelopmental disorder). "in utero", intracranial injection of ASO resulted in dose-dependent activation of paternal Ube3a, with broad biodistribution. Accordingly, "in utero" injection of ASO in a mouse model of Angelman syndrome also resulted in successful restoration of UBE3A and phenotypic improvements in treated mice on the accelerating rotarod and fear conditioning. Strikingly, even intra-amniotic injection resulted in systemic biodistribution and high levels of UBE3A reactivation throughout the brain. These findings offer a novel strategy for early treatment of Angelman syndrome using an ASO, with two potential routes of administration in the prenatal window. Successful delivery of a therapeutic ASO into neurons has implications for a clinically feasible prenatal treatment for numerous neurodevelopmental disorders. #AntisenseOligonucleotides , #ASO #Oligonucleotides #RNAtherapeutics #RNAi #Neurodevelopmental disorder #Neurologicaldisorders . https://lnkd.in/dHZ32NWg .

PRETERM INFANT MICROBIOME PREDICTS NEURODEVELOPMENTAL DEFECTS -MICROBIOME TRANSPLANTATION COULD BE THE ANSWER https://lnkd.in/eMKYwKXh #infantmicrobiome Research led by the University of Chicago shows an artificial intelligence (AI) driven “digital twin” modeling the infant microbiome can predict neurodevelopmental problems later in infancy. Using data on very early gut microbiome composition from fecal samples from preterm babies the digital twin predicted later microbiome composition and associated neurodevelopmental deficits with a high degree of accuracy. The researchers found that the digital twin was able to predict risks for suboptimal development and poor head circumference growth (HCG) with a 76% area under the receiver operator characteristic curve score. It had a 95% positive predictive value and 98% specificity at 30 weeks of gestation. This recent study demonstrated Bacteroidia was depleted in preterm infants with Suboptimal Head Circumference Growth (SHCG) and that Actinobacteria was further diminished in preterm infants with moderately severe SHCG, as had been reported in an earlier analysis conducted at the UChicago. The importance of these taxa to infant development has been substantiated through multiple observational and in vivo studies. For example, the relative under-abundance of Bacteroidia has been associated with autism spectrum disorder and attention deficit/hyperactivity disorder. Mechanistically, Bacteroidia may affect neurodevelopment by strengthening intestinal barrier integrity and changing the systemic metabolite profile. Treatment of the maternal immune activation mouse model of autism spectrum disorder with Bacteroides fragilis has been directly shown to ameliorate behavioral defects, increase intestinal tight junction protein expression, and alter metabolite levels in the sera. In addition, the principal genus of Actinobacteria in the infant gut is Bifidobacterium, whose relative abundance has been implicated or associated with improved temperamental traits extraversion and soothability and fine motor skills. In terms of mechanism, treatment of the propionic acid rat model of autism spectrum disorder with Bifidobacterium longum has been shown to rescue social deficits and normalize brain-derived neutrophic factor levels in the hippocampal region of the brain. The researchers calculated that early microbiome transplantation could potentially have helped around 45% of the cohort avoid developmental problems.

#alzheimer's #viagra #PDE5 #SILDENAFIL Does Viagra help to protect against Alzheimer's? A study has found a link between taking erectile dysfunction drugs and a lower risk of developing Alzheimer's disease, but it is far from definitive, finds Clare Wilson ANYONE considering using Viagra as a treatment for impotence could be forgiven for thinking there is now another reason to go ahead with it. Some news headlines say that this class of drugs, known as PDE5 inhibitors, protects people from developing Alzheimer's disease. The stories are based on a study by Ruth Brauer at University College London and her colleagues. They looked at anonymised medical records of nearly 270,000 men in the UK aged 40 or older who had a new impotence diagnosis. Those who went on to get prescriptions for Viagra (sildenafil) or a similar drug had an 18 per cent lower chance of being diagnosed with Alzheimer's over the next five years (Neurology, doi.org/mf8v). It isn't implausible that this class of drug could protect against dementia. These therapies are being investigated for several conditions, including to help protect babies from oxygen deprivation during childbirth, and Viagra was originally developed as a treatment for heart disease. The drugs work by raising levels of a signalling molecule called GMP that dilates blood vessels and so boosts blood flow to the penis. Animal research has shown that the drugs also dilate blood vessels to the brain, which may keep it in better shape. A second potential mechanism is that they raise levels of a nerve signalling molecule called acetylcholine, which could help brain cells communicate with each other. Indeed, some existing medicines that slightly alleviate dementia symptoms work by boosting acetylcholine. But we need to be careful about drawing conclusions from this kind of study. It wasn't a randomised trial, where, for instance, hundreds of men would be given either Viagra or placebo pills and their subsequent rates of Alzheimer's compared. This type of study is prone to bias because a third factor could be linked with Viagra use and be protective against Alzheimer's disease. Bauer's team adjusted their results for several possible confounding factors, including age and many health aspects. But they couldn't take account of the men's physical activity levels, as this wasn't listed in their medical records. It is plausible that men who sought prescriptions for impotence pills were also more physically active and it was this that guarded against dementia. "We know that activity protects against Alzheimer's disease," says Bauer. The latest results aren't, therefore, a reason to see these drugs as a silver bullet for preventing dementia, with the added bonus of treating erectile dysfunction. "Our study can't say for sure it's the drugs that are responsible for the protective effect," says Bauer. They may, however, be a stimulus for carrying out randomised trials in the hope this will provide firmer evidence.

As someone who received a BCG vaccine as a baby in India, this headline caught my attention. During my fellowship training in Integrative Psychiatry, this concept of retraining ‘immune tolerance’ was discussed repeatedly in the context of treating neuroimmune dysregulation and inflammation as the root cause of mental disease. These remarkable effects are thought to emerge from a process called “trained immunity”. After an individual has received BCG, you can see changes in the expression of genes associated with the production of cytokines – small molecules that can kick our other defences, including white blood cells, into action. As a result, the body can respond more efficiently to a threat – be it a virus or bacteria entering the body, or a mutant cell that threatens to grow uncontrollably. Animal studies provide some tentative evidence. Laboratory mice immunized with BCG have reduced brain inflammation, for example. This results in notably better cognition, when other mice of the same age begin to show a steady decline in their memory and learning. But would the same be true of humans? The role of Bacillus Calmette-Guérin administration on the risk of dementia in bladder cancer patients was looked at through a systematic review and meta-analysis. The precise level of protection varies between studies, with this recent meta-analysis showing an average risk reduction of 45%. If this can be proven with further studies, the implications would be huge. BCG administration is associated with a significantly lower risk of developing dementia. However, an epidemiological cohort is needed to establish a relationship between BCG use and incident dementia in the normal population. In the meantime, scientists have started to examine certain biomarkers that show the early stages of disease. Until recently, this was extraordinarily difficult to do without expensive brain scans, but new experimental methods allow scientists to isolate and measure levels of amyloid beta proteins in blood plasma, which can predict a subsequent diagnosis with reasonable accuracy. A pilot study at the University of Wisconsin-Madison suggests that BCG injections can effectively reduce plasma amyloid levels, particularly among those carrying the gene variants associated with a higher risk of Alzheimer’s. Although the sample size was small – just 49 participants in total – it has bolstered hopes that immune training will be an effective strategy for fighting the disease. Shared via Professor Erwin Loh https://lnkd.in/gzXsh45E Study: https://lnkd.in/gVBwytvR