ACTA2 Alliance’s Post

Are Disease-Modifying Treatments on the Horizon for Patients With #ARVC? Gene therapy targeting the underlying desmosomal mutation and approaches to prevent myocardial fibrosis independent of the specific genetic defect by increasing cardiac levels of FGF21 may be on the horizon for patients. https://okt.to/mOF1sy

Cool paper in Developmental Cell: Identifying FUS amyotrophic lateral sclerosis disease signatures in patient dermal fibroblasts https://lnkd.in/eb65z6Xk Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, highly heterogeneous neurodegenerative disease, underscoring the importance of obtaining information to personalize clinical decisions quickly after diagnosis. Here, we investigated whether ALS-relevant signatures can be detected directly from biopsied patient fibroblasts. We profiled familial ALS (fALS) fibroblasts, representing a range of mutations in the fused in sarcoma (FUS) gene and ages of onset. To differentiate FUS fALS and healthy control fibroblasts, machine-learning classifiers were trained separately on high-content imaging and transcriptional profiles. “Molecular ALS phenotype” scores, derived from these classifiers, captured a spectrum from disease to health. Interestingly, these scores negatively correlated with age of onset, identified several pre-symptomatic individuals and sporadic ALS (sALS) patients with FUS-like fibroblasts, and quantified “movement” of FUS fALS and “FUS-like” sALS toward health upon FUS ASO treatment. Taken together, these findings provide evidence that non-neuronal patient fibroblasts can be used for rapid, personalized assessment in ALS.

Study published in Nature, unveils an intriguing transcriptional pause/release mechanism that empowers macrophages to efficiently engulf and digest numerous apoptotic cells, facilitating homeostasis. Understanding and potentially modulating this mechanism holds promise for addressing various diseases linked to aberrant macrophage activity, including chronic inflammation, cancer, autoimmune disorders, and more. This insight opens avenues for therapeutic interventions to improve patient outcomes. https://lnkd.in/gYQqrKBW

New research into TTN gene variants and their impact on cardiac health has a tangible and lasting effect on the lives of ipeople and families dealing with these conditions. It offers hope for 💡earlier diagnosis, 💡tailored treatments, 💡informed decision-making, 💡emotional support, and 💡continued advancements in medical care. Thanks Eldar Dedic for the summary. https://lnkd.in/dA_FEVTC #Genomics #genetics #diagnosis #tailoredtreatments

Have you heard about #Elevidys ? In recognition of September as the awareness month for Duchenne muscular dystrophy, I'd like to share some insightful facts about this condition, paying tribute to the patients it affects. Duchenne muscular dystrophy (DMD) is a rare and severe genetic disorder that primarily affects muscle function. It is caused by a mutation in the DMD gene, which leads to the absence or deficiency of a protein called dystrophin. Dystrophin is essential for maintaining the structure and strength of muscle fibers. Key characteristics and facts about Duchenne muscular dystrophy include: 👉 Onset: DMD typically becomes evident in early childhood, often between the ages of 3 and 5. 👉 Symptoms: Common symptoms include progressive muscle weakness, difficulty in walking and standing, loss of motor function, and a tendency to develop muscle contractures. 👉 Muscle Degeneration: Over time, muscle tissue is replaced by fat and connective tissue, leading to muscle wasting and weakness. 👉 Mobility Challenges: Children with DMD often require mobility aids like wheelchairs as the disease progresses. 👉 Respiratory and Cardiac Issues: DMD can also affect the respiratory and cardiac muscles, leading to breathing difficulties and heart problems. DMD is an X-linked recessive genetic disorder, primarily affecting males. Females can be carriers of the mutation but are usually asymptomatic. #ELEVIDYS is a prescription gene therapy used to treat ambulatory children aged 4 through 5 years old with Duchenne muscular dystrophy (DMD) who have a confirmed mutation in the dystrophin gene. Elevidys is a recombinant gene therapy designed to deliver into the body a gene that leads to production of Elevidys micro-dystrophin, a shortened protein (138 kDa, compared to the 427 kDa dystrophin protein of normal muscle cells) that contains selected domains of the dystrophin protein present in normal muscle cells. The product is administered as a single intravenous dose. #DMD #duchennemusculardystrophy #duchenneawareness #genetics #rarediseases #proteins

Reporting Cases of Intermediate #NerveConductionVelocity in Patients with #CharcotMarieTooth Disease Type 1A New research from the Inherited #Neuropathy Consortium (INC): https://lnkd.in/gA-7Z2cd Charcot-Marie-Tooth disease type 1A (CMT1A), the most common form of inherited peripheral neuropathy, is caused by duplication of the PMP22 gene. Individuals with CMT1A experience slow nerve conduction velocity (the speed of electrical impulses moving through nerves). Because most patients have nerve conduction rates below 38 meters per second, genetic testing for PMP22 duplication is not usually recommended for those with higher rates. In this study, researchers report cases of intermediate nerve conduction velocity in two patients with CMT1A. Both individuals had upper limb motor nerve conduction velocities above 38 meters per second. These patients also presented with very mild forms of CMT1A. Authors note that although these cases are very rare, they highlight the importance of testing PMP22 duplication in patients with intermediate conduction velocities.

https://lnkd.in/ekXPQpvj Article title: Acute Panmyelosis with Myelofibrosis: The Serpentine Road to Diagnosis   Author(s): Celia Suriu; Andrei Braester; Masad Barhoum Journal: Annals of Bone Marrow Research   Journal ISSN: 2692-4684 Abstract: cute Panmyelosis with Myelofibrosis (APMF) is an extremely rare disease. Lack of familiarity with this rare subtype of acute leukemia hinders the diagnosis [1]. It is characterized by an acute, rapidly progressive, fatal clinical course, peripheral blood cytopenias with minimum 20% blast and no detectable splenomegaly. APMF corresponds to less than 1% of the cases of Acute Myeloid Leukemia (AML) [2]. Histologically, APMF is characterized by a heavily fibrotic marrow, an increased number of immature hematopoietic elements (panmyelosis), and dysplastic population of megakaryocytes. The condition should be differentiated from other hematological neoplasms that present with fibrosis such as acute megakaryoblastic leukemia and myelodysplsia (MDS) with myelofibrosis. Dacrocytes are not present.   #BoneMarrow #BloodSamples #Hematology #AutoimmuneDiseases #StemCells #Immunology #Transplantation #MinimalInvasiveSurgeryTechniques #TranscriptionFactors #Medication #TropicalTreatments #Metabolism #Mortality #DrugTargeting #DrugSensitivity #Resistance #HabitsAndLifestyle #PrognosticFactors #Pathophysiology #NovelDrugs #CellularTherapy #TranslationalResearch #MesenchymalStemCell #HematopoieticStemCellTransplantation #BoneMarrowTransplantation #BoneMarrowEdema #BoneMarrowCancer #BoneMarrowBarrier    

Did you know? LCA was first identified by the German ophthalmologist Theodor Leber in 1869, it has since been studied extensively, bringing hope for better understanding and treatment. Over the years, advancements in genetics and ophthalmology have shed light on the complex mechanisms underlying LCA. With the discovery of various genetic mutations associated with the condition, researchers have made significant strides in developing targeted therapies and gene therapies aimed at restoring vision. Hope in Focus is dedicated to raising awareness and supporting research efforts to combat LCA and other retinal diseases. Together, let's continue spreading hope and empowering those affected by vision loss. More about LCA : https://loom.ly/gs7sJ1Y Information regarding LCA's History: https://loom.ly/AZyKq5Y # LCA #LeberCongenitalAmaurosis #HopeInFocus #HIF #FunFacts

How do macrophages eat so much?? In this elegant paper, out today in Nature, the Ravichandran team describes a fascinating transcriptional pause/release mechanism that enables macrophages to rapidly engulf and consume multiple apoptotic cells to achieve homeostasis. Targeting this mechanism in the many disease states that arise/persist due to faulty macrophage function (such as chronic inflammation, cancer, autoimmune disease, etc) could benefit patients.