Ana Rosalina Arutiunian Medina’s Post

The convergence of three primordial cellular functions — autophagy, immunity and mitochondrial function and their intimate association with Parkinson’s disease (PD) RAB GTPase, RAB32 Ser71Arg, is a novel genetic risk factor for PD, with reduced penetrance. The variant was found in individuals with PD from multiple ethnic groups, with the same haplotype. RAB32 Arg71 activates LRRK2 kinase and is the first gene identified that directly connects the dots between earlier discoveries and optimization of the levels of the neurotransmitter dopamine, which is lost in PD as cells that produce it progressively die. https://lnkd.in/diDWR5zV

🚨 New Publication Alert! 🚨 I'm excited to share my latest research on the connection between vulnerability to infections and Alzheimer's disease (AD), recently published under the title "Understanding the Role of NECTIN2 Gene and pTau-181 in Alzheimer's Disease." We report a new potential causal relationship between pTau-181 and AD, highlighting the complex interplay between genetic susceptibility, protein aggregation, and neurodegeneration. https://shorturl.at/tx276 #Alzheimer’s disease, #NECTIN2 gene, #rs6859, #pTau-181, #Causal Mediation

Breaking news! A recent study published in The Lancet has highlighted the role of the RAB32 gene in the etiology of Parkinson's disease. The study identified a novel mutation, Ser71Arg, in three probands. Through a case-control study, the authors found this same mutation in additional cases. The RAB32 gene can now be added to your neurological panel! #CLIA #CAP #COLA #NGSvalidation

Inflammation and fibrosis are key drivers of chronic liver diseases like MASLD. Inflammation triggers immune responses and cytokine production, which can lead to fibrosis—excess tissue build-up that impairs liver function. Accurate models of these processes are crucial for understanding disease progression.   A recent publication on in #Nature #ScienctificReports highlighted significant differences between normal and MASH Primary Human Hepatocytes inflammation and fibrosis.   Diseased PHH notably show:  Higher expression of pro-inflammatory cytokines Increased macrophage marker gene expression Elevated fibrotic markers   This study demonstrates TruVivo's ability to realistically simulate inflammation and fibrosis, proving to be a valuable tool for MASLD progression research.   Check out the full article here: https://lnkd.in/dFqguJbT

Serendipitously, my post a few minutes ago about a great book on hereditary cancer syndromes (A Fatal Inheritance) led me to this post regarding a new study involving a non-cancer hereditary disease. Specifically, this study involves genetic engineering approaches to helping people with a severe cardiac issues arising from pathogenic inherited mutations of the LAMP2 gene. IMO, it is virtually impossible to overstate the importance of funding both basic and applied research to better understand and treat hereditary diseases, and to provide related genetic counseling and therapies. #hereditarydisease #cancersyndromes #cancer #geneticepidemiology #riskmanagement #healthscreening #healthinsurance #geneticcounseling

ANNOUNCEMENT – This is the second part of the third post in our series about rare diseases. In part 1 we discussed gene silencing in general; here, we discuss one form (antisense oligonucleotides) that’s proving increasingly interesting as a potential therapy for a wide range of neurodegenerative disorders. So, to start, nucleotides are molecules that form the basic structure of DNA and RNA. Oligo is from the Greek and means ‘just a few’. So oligonucleotides are short pieces of modified DNA, typically comprising around 20 nucleotides. mRNA is a copy of DNA that travels from the nucleus to another part of the cell where proteins are made. It is the ‘sense’ part of mRNA that results in a protein. Antisense oligonucleotides (ASOs) are called antisense because they bind to the sense part of mRNA, in a complementary manner, preventing it from producing its associated protein.   ASOs are currently in trials for Alzheimer’s disease (University College London Hospital), where they have already demonstrated promising results, and are being investigated as potential therapies for Parkinson’s and Motor Neuron Disease. We are determined to get to clinical trials as soon as possible with our candidate ASO for treating H-ABC.

Inherited retinal dystrophies (IRDs) affect approximately 1 in 2,000 people worldwide, making them one of the leading causes of blindness. Autosomal dominant type of inheritance is common among others for retinal diseases (adIRDs). It happens when a single faulty gene is inherited from an affected parent, which is enough to cause the disease. Even within the same family, diagnosing of adIRDs can be challenging due to the wide variation in symptoms. Some individuals may exhibit symptoms early in life, while others may develop noticeable signs only later in adulthood, or show only mild symptoms. Despite their impact, adIRDs remain underrepresented in retinal disease research. However, the discovery of new genetic causes for autosomal dominant retinal dystrophies is crucial for improving detection rates and enabling timely treatment. Our team of 10 PhD students is dedicated to advancing the understanding of these conditions. We are investigating how adIRDs develop, uncovering new genetic factors, studying their biological effects across multiple levels, and exploring gene therapy as a potential treatment. Through our research, we aim to accelerate diagnosis and improve treatment options, offering hope to families affected by adIRDs. Stay tuned for updates as we make progress in understanding and combating these inherited eye diseases!

[INTERNATIONAL CRIGLER-NAJJAR DAY] 🌻This Friday, June 21, our teams are supporting #CriglerNajjarDay, an worldwide day dedicated to Crigler-Najjar syndrome, a rare genetic liver disease. It is characterized by the abnormal accumulation in all body and brain tissues of bilirubin, a yellow-pigmented substance produced by the liver, which can lead to severe neurological damage and death. Only phototherapy, lasting from 10 to 12 hours a day, remains the mainstay of long-term  treatment for patients suffering from this syndrome and thus enables  bilirubin levels to be reduced, but it considerably impairs patients' quality of life. 💙An international gene therapy clinical trial, sponsored by Genethon, began in 2018. The first results published in 2023 in the New England Journal of Medicine demonstrated the efficacy of this #GeneTherapy treatment designed by the «Immunology and liver diseases team» led by Giuseppe Ronzitti. The pivotal part of the trial has been initiated enabling the inclusion children 10 years old and over. 👉 https://vu.fr/BbKwx Giuseppe Ronzitti Fanny Collaud #genethon #raredisease #clinicaltrials #Liver #GeneTherapy

Multiple myeloma (MM) is a genetically diverse disease hallmarked by the clonal expansion of plasma cells. This clonal outgrowth makes MM incredibly difficult to treat acutely—patients often relapse after treatment and require multiple treatments, with failures often attributed to the clonal heterogeneity of the disease. In our latest blog, we explore the genetic diversity of MM, the molecular attributes that can help us better understand the disease, and how single-cell analysis and the Tapestri Platform can help researchers gain crucial insights into the clonal heterogeneity and evolution underlying myeloma progression, therapy response, and relapse. Read it here 👉 https://lnkd.in/gsHdyJMe

The era of precision therapy for inherited cardiovascular disease is upon us. For years we had almost nothing to offer patients with severe inherited cardiomyopathy — certainly no therapies focused on the underlying mechanism of disease. We are now on the verge of a new chapter with dozens of genetic-based therapies entering clinical trials. In today's NEJM and presented at the American Heart Association meeting, a notable report of cardiac directed gene therapy. Danon disease is a severe progressive X-linked storage disorder causing cardiomyopathy and early death in males. It is caused by loss of function mutations in the LAMP2 gene. In this study, 7 boys received a LAMP2B transgene packaged in AAV9. Side effects were significant but transient and reversible. In one case, the disease continued to progress. In 6 cases, there was evidence of cardiac expression of the missing protein and stabilization or improvement of clinical features. These are remarkable results and while it is very much early days, this represents new hope for millions of patients worldwide with severe inherited cardiovascular disease. https://lnkd.in/gyyiQ9kC