EURORDIS-Rare Diseases Europe’s Post

#NAFLD #NASH #OpenAccess #MedEd 📖 Dr. Zachary J. Brown's team: Alteration in immune function in patients with fatty liver disease. 🏷 Download: https://lnkd.in/gBw48d-7 ✔ NASH is a multifactorial, complex, immunologic disease that results in severe liver alterations. A vast network of immune cells is mobilized and functionally changed in patients with NASH, resulting in a persistent driving force for the progression of cirrhosis and HCC. While we have described a few of the immune alterations above in both the innate and adaptive immune systems, there are still many mechanisms responsible for steatohepatitis that are incompletely understood. At this time, further studies are needed to elicit a more robust understanding of the complex immune pathophysiology of this disease. Hope this will be an interesting reading! Antonio J Sanchez, MD Andrew Fowell Gene Im Edoardo Poli James Spivey Jonathan Fenkel, M.D., FACP, FAASLD Antonio Liguori Bernard Partiula Bernard Partiula

Dominant NARS1 mutations causing axonal Charcot–Marie–Tooth disease expand NARS1-associated diseases. #RareDisease #Genetics Despite pathogenic variants in NARS1 cause a neurological phenotype combining developmental delay, ataxia and demyelinating peripheral neuropathy, no link to axonal Charcot–Marie–Tooth disease has yet been described. In this study, they present three previously unreported NARS1 variants segregating with a sensorimotor neuropathy phenotype in three families, with variable severity and—in one case—additional CNS features including mild spasticity and cerebellar ataxia. https://lnkd.in/dM-MtJhY

Rare Disease Show Episode 13 - Understanding Canavan Disease Ft. Dr Praveen Kumar Medical Dialogues presents a rare disease series, delving into the realm of uncommon medical conditions. Rare diseases are medical conditions that affect only a small percentage of the population. Throughout this series, we'll discuss these rare diseases in various episodes, with medical experts providing clear explanations and insights. Rare Disease Show Episode 13 -- In today's show we will cover Canavan Disease. Canavan disease is a rare genetic disorder that primarily affects the brain's white matter. It is caused by mutations in the ASPA gene, leading to a deficiency of the enzyme aspartoacylase. This enzyme is essential for breaking down N-acetylaspartic acid (NAA), a compound found in the brain. For more information, click on the link below: https://lnkd.in/d9S2GPMt #rarediseae #canavandisesase #disease #drpraveenkumar #canavan #medicaldialogues

Prion diseases, a brain disorder that causes rapid neurodegeneration and death, are caused by misshapen versions of the prion protein. This leads to a cascade effect in the brain in which defective prion proteins deform other proteins, resulting in toxic aggregates that kill neurons. The most famous form, known as mad cow disease, is infectious, but other forms can occur spontaneously or be caused by faulty prion protein genes. Silencing genes in the brain has been challenging, with methods such as antisense oligonucleotides and CRISPRoff requiring repeated spinal injections and large amounts of adeno-associated viruses (AAVs). A study published in Science Magazine describes Coupled Histone Tail for Autoinhibition Release of Methyltransferase (CHARMs), which work by silencing the gene PRNP that codes for the faulty protein. CHARMs do this through epigenetic editing, which is stable and requires patients to receive CHARM-based therapy only once. Tests in mice have shown that CHARMs can eliminate more than 80% of the prion protein in the brain, while previous research has shown that eliminating as little as 21% can improve symptoms. However, naturally occurring types of AAV do not efficiently enter the adult brain, making it impossible to treat whole-brain diseases such as prion disease. A group at the Broad Institute of MIT and Harvard designed an #AAV vector that can enter the brain more efficiently by using a pathway that naturally transports iron into the brain - this AAV vector provided 40 to 50 times greater reporter expression in the CNS of human TFRC knockin mice. The team behind CHARM study is now fine-tuning their tool to make it more effective, safer, and easier to produce at scale for clinical trials. They have made the tool modular so that different parts and future CHARMs can be easily swapped out. https://lnkd.in/eisd4X5s

Mutations in the TBX4 gene can cause not only heritable pulmonary arterial hypertension (HPAH) in children but also skeletal anomalies causing issues with the knee and hip joints. TBX4 mutations can cause another serious illness, Interstitial Lung Disease in Childhood (chILD), which is also incurable. Anton Morkin is the father of a young boy who carries the TBX gene mutation and has pulmonary arterial hypertension. He is the Founder of the TBX4Life website and community. Anton started in 2020 to search and connect families affected by TBX4 Syndrome. Since pulmonary arterial hypertension is the most severe consequence of it, he says, many members of the TBX4 community join after their diagnosis and after genetic testing in one of the affected family members. However, the community also has members who are not affected by pulmonary arterial hypertension. As of today many families from the USA, UK, several countries from the EU (like Germany, France, Netherlands, etc) and also from Australia and New Zealand have joined the movement. Read more at this link on the Pulmonary Hypertension Knowledge Sharing Platform https://lnkd.in/dmpq8CXt #pulmonaryhypertension #pulmonaryarterialhypertension #PAH #chronicthromboembolicpulmonaryhypertension #CTEPH #knowledgesharing #knowledgeexchange #patientempowerment #patienteducation #allianceforph #organtransplant #organdonation #transplant #lungtransplant #geneticph

A new study sheds light on factors influencing diagnosis in rare diseases. Through examining 400 diagnosed and undiagnosed patients in the Undiagnosed Diseases Network, researchers have found some factors reducing the odds of diagnosis such as adult symptom onset and prior exome sequencing and genome sequencing. On the other hand, neurological symptoms and previous chromosomal microarray testing increased diagnostic odds by 44% and 59%. Through these insights and understanding of what affects diagnosis, we can optimize the use of sequencing to resolve undiagnosed cases. Read here: https://lnkd.in/g497Z5Hr #rarediseases #genomics #genomicmedicine #sequencing

Why Do Some People Get Severe Flu or COVID-19? A New Gene Discovery Might Hold the Answer A recent study published in Cell has uncovered a surprising factor that could explain why some individuals experience severe respiratory infections, such as flu, COVID-19, and RSV, while others only have mild cases. Key Takeaways: ➡ The OLAH Gene: Researchers identified a gene called OLAH (oleoyl-acyl-carrier-protein hydrolase) that may influence the severity of respiratory viral infections. ➡ Dual Role of OLAH: The enzyme produced by this gene plays a dual role—it increases inflammation and aids viral replication, which can worsen the severity of the disease. ➡ Higher Levels in Severe Cases: Patients with severe illness or death from these infections had significantly higher levels of OLAH in their blood. ➡ Promising Research: Experiments in mice showed that reducing OLAH expression significantly decreased mortality from influenza, suggesting a potential target for future treatments. ➡ Implications for Long COVID: Understanding the role of OLAH could also help us unravel the complexities of Long COVID-19, providing insights into why some patients experience prolonged symptoms. Why It Matters: This research could help us better understand and combat severe respiratory infections, offering new strategies for treatment and prevention. [Read the full article here: https://lnkd.in/eJWA6-Je] #COVID19 #Flu #LongCOVID #Genomics #HealthcareInnovation #Science

🟠 This time, the Neanderthal genome caused resistance to this autoimmune disease! 🔸️ Membrane nephropathy (MN) is a rare autoimmune kidney disease that affects 10 to 12 people out of one million people. Despite the rarity of this disease, it is one of the main causes of nephrotic syndrome in European adults. This disease occurs when the small blood vessels in the kidney (glomerulus), which have the role of purifying the blood, become inflamed, and as a result, protein enters the urine from the damaged vessels. This disease is accompanied by an increase in PLA2R1 gene expression. 🔸️ But what is the connection between this disease and Neanderthals? Around 300,000 years ago, Neanderthals spread across Eurasia, from Asia to Europe. 300,000 years was the an adequate time for them to fully adapt themselves to the environment. But our ancestors entered Europe around 55,000 years ago and encountered the indigenous Neanderthal population. The interaction between the two groups took place in 3 ways: avoidance, conflict and interbreeding. 🔸️ Due to interbreeding, about 1 to 3% of our genome belongs to Neanderthals, its distribution is more concentrated in some areas of the genome and is not present at all in some areas, which itself expresses the effect of natural selection as a mechanism to preserve some of these ancient variants. 🔸️ This scenario seems logical, considering that our newly arrived ancestors were less adapted to the new environment, because the native Neanderthal population had traits that increased their survival and these traits were transferred to our ancestors through interbreeding and preserved through natural selection and passed down to the next generation, including skin thickness and hair density that were more efficient in the colder European climate. 🔸️ Immunity is also one of the traits affected by Neanderthal variants, and there is a strong link between Neanderthal variants, infections and autoimmune disorders such as rheumatoid arthritis, MS, lupus, Crohn's, Graves and type 2 diabetes. 🔸️ In this review, the researchers investigated the disease of membranous nephropathy. By examining the genomes of Neanderthals and modern humans, 2 Neanderthal variants were identified that were associated with a lower expression of the PLA2R1 gene, which in turn causes a protective effect against this disease. 🔸️ The interesting point of this study is that until now it was thought that all variants inherited from Neanderthals mainly contribute to the increased susceptibility of carriers to autoimmune disorders (as mentioned in the examples above). But this study is an interesting example of Neanderthal variants protecting against autoimmune disorders in modern humans. 🖋 Sahar Mortezanejad ✅️ Reference: https://lnkd.in/exiuZvap

I am pleased to share our 1st paper of the year on the role of senescent astrocytes in the pathology of cerebral malaria. #Center for Infection and Immunity of Lille Institut Pasteur de Lille

Genetic testing can provide valuable insights into potential health risks, as seen in St. Luke's University Health Network's DNA Answers program. Offering free testing for conditions like hereditary breast and ovarian cancer syndrome and Lynch syndrome, this initiative aims to identify genetic markers early for preventative health measures. By participating in genetic testing programs, individuals can take proactive steps towards personalized healthcare and disease prevention. Hashtags: #GeneticTesting #PreventativeHealth #PersonalizedMedicine #DiseasePrevention #PopulationGenomics Read more here: https://lnkd.in/ep7pz6Jj BioMedHack.com is your leading source for the latest news, breakthroughs, and insights in medicine, biohacking, and alternative medicine. Our mission is to help you live healthier and longer by bringing you cutting-edge information and expert advice. Follow us on Facebook, Instagram, and X.