• WALTHAM, Mass., Sept. 20, 2023 (GLOBE NEWSWIRE) -- Dyne Therapeutics, Inc. (Nasdaq: DYN), a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for DYNE-101 for the treatment of myotonic dystrophy type 1 (DM1). (tmcnet.com)
  • DYNE-101 is an investigational therapeutic being evaluated in the Phase 1/2 global ACHIEVE clinical trial for people living with myotonic dystrophy type 1 (DM1). (tmcnet.com)
  • The major forms of MD include Duchenne MD (DMD), Becker MD (BMD), limb-girdle MD (LGMD), facioscapulohumeral dystrophy (FSHD), myotonic dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2), congenital MD (CMD), oculopharyngeal MD (OPMD), distal MD (DMD), and Emery-Dreifuss MD (EDMD). (medscape.com)
  • Myotonic dystrophy type 1: from DNA repeat expansion and toxic RNA to the development of new therapeutic approaches. (ern-euro-nmd.eu)
  • Mario Gomes-Pereira has been working on myotonic dystrophy type 1 (DM1) and related trinucleotide repeat expansion disorders for more than 20 years. (ern-euro-nmd.eu)
  • Arnaud Klein has been working on myotonic dystrophy type 1 (DM1) and more generally on repeat expansion diseases for nearly 20 years. (ern-euro-nmd.eu)
  • In this team, Arnaud was able to develop innovative therapeutic approaches for Myotonic Dystrophy type 1, notably using antisense oligonucleotides, and to participate in the development of several DM1 models. (ern-euro-nmd.eu)
  • A CTG repeat element normally resides in the 3' untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene, but when expanded it is the genetic lesion of myotonic dystrophy type 1 (DM1), a hereditary neuromuscular disease. (bvsalud.org)
  • Fu cloned one of the genes responsible for a form of muscular dystrophy called myotonic dystrophy, and showed that an expanded trinucleotide repeat in this gene also was unstable and caused the disease. (wikipedia.org)
  • point stop mutations), hemophilia ( A , B ), phenylketonuria -PKU (point mutation), Duchenne muscular dystrophy (DMD) , adenosine deaminase (ADA) deficiency causing severe combined immune deficiency (SCID), Tay-Sachs disease (hexosaminidase A deficiency). (dorak.info)
  • He worked under the supervision of Dr Bernard Brais to understand the pathological mechanisms leading to the Oculopharyngeal Muscular Dystrophy (OPMD), a disease characterized by a late-onset muscular dystrophy, a triplet expansion mutation in a ubiquitous gene and the formation of intranuclear aggregates. (ern-euro-nmd.eu)
  • Myotonic dystrophy (DM) is the most common autosomal dominant muscular dystrophy and encompasses both skeletal muscle and cardiac complications. (jci.org)
  • They cloned the causative gene/mutation and studied the in vitro biochemical consequences of the mutation, culminating in a 2001 paper An hPer2 phosphorylation site mutation in familial advanced sleep-phase syndrome, reporting the first circadian gene mutation in humans. (wikipedia.org)
  • The lab studied the genomes of people with this trait and found a point mutation in the PER2 gene that likely causes the behavioral phenotype. (wikipedia.org)
  • Anticipation typically occurs with disorders that are caused by an unusual type of variant (mutation) called a trinucleotide repeat expansion. (medlineplus.gov)
  • Type 2 DM (DM2) is milder and involves a CCTG repeat expansion mutation of the cellular nucleic acid binding protein gene CNBP (previously known as ZFN9) on chromosome 3q21.3. (msdmanuals.com)
  • For instance, if you've got a mutation caused by triplet repeat expansion, for instance in the Huntington's gene, where the trinucleotide repeats a CAG, you might have 17 CAGs in a normal chromosome. (hstalks.com)
  • Some occur in the coding region of the gene, others occur in the five prime region and others occur in the three prime region, and these have different consequences on the function of the gene and the results of the mutation. (hstalks.com)
  • Because of the number of diseases in this slide, I've chosen to focus on those in boxes for the most part, and I've chosen to focus on them because I think they illustrate the key genetic principles underlying this class of mutation. (hstalks.com)
  • DYNE-101 consists of an antigen-binding fragment antibody (Fab) conjugated to an antisense oligonucleotide (ASO) and is designed to enable targeted muscle tissue delivery with the goal of reducing toxic DMPK RNA in the nucleus, releasing splicing proteins, allowing normal mRNA processing and translation of normal proteins, and potentially stopping or reversing the disease. (tmcnet.com)
  • Dyne has generated comprehensive preclinical data supporting its DM1 program, including reduction of nuclear foci and correction of splicing in patient cells, robust knockdown of toxic human nuclear DMPK RNA and correction of splicing in a novel in vivo model developed by Dyne, and reversal of myotonia in a disease model. (tmcnet.com)
  • It is a monogenic, autosomal dominant disease caused by an abnormal trinucleotide expansion in a region of the DMPK gene. (tmcnet.com)
  • Type 1 DM (DM1) involves expansion of a CTG trinucleotide repeat of the DMPK gene located on chromosome 19. (msdmanuals.com)
  • The pathogenic DMPK transcript containing the CUG expansion is retained in ribonuclear foci as part of a complex with RNA-binding proteins such as muscleblind-like 1 (MBNL1), resulting in aberrant splicing of numerous RNA transcripts and consequent physiological abnormalities including myotonia. (bvsalud.org)
  • CRISPR-CAS9 is a system of gene editing (precisely, the precise/specific gene-editing tool) having lucrative applications in medical research, diagnostics, animal research, plant and agriculture science. (geneticeducation.co.in)
  • What is gene editing and CRISPR CAS9? (geneticeducation.co.in)
  • While there, she was part of the team that identified the fragile-X syndrome gene. (wikipedia.org)
  • All homologous chromosome pairs contain two variant forms of the same gene , called " alleles ," which are passed down from parent to offspring. (amboss.com)
  • In Cri-Du-Chat syndrome (5p deletion), the genetic basis of the phenotype is haploinsufficiency for the telomerase reverse transcriptase gene ( TERT ), which is included in the deleted part of chromosome 5. (dorak.info)
  • But in a diseased chromosome, you might have 40 successive copies of CAG trinucleotides in the gene. (hstalks.com)
  • Myotonic dystrophy is nucleotide repeat expansion disorder in which type 1 (DM1) is due to a trinucleotide repeat expansion on chromosome 19 and type 2 (DM2) arises from a tetranucleotide repeat expansion on chromosome 3. (jci.org)
  • Her chief discoveries include describing Mendelian sleep phenotypes, identifying causative genes and mutations for circadian rhythm disorders, and characterizing genetic forms of demyelinating degenerative disorders. (wikipedia.org)
  • Autosomal Dominant Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. (msdmanuals.com)
  • One of these genes, cys-3, encodes a leucine zipper protein. (wikipedia.org)
  • The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase. (lookformedical.com)
  • These mice express the human htt cDNA which encodes glutamine and the first 171 amino acids bearing 82 CAG repeats (Schilling et al. (edubirdie.com)
  • Innate immunity is central to the pathophysiology of neurodegenerative disorders, but it remains unclear why immunity is altered in the disease state and whether changes in immunity are a cause or a consequence of neuronal dysfunction. (shengsci.com)
  • These disorders include motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), which may involve motor neurons in the brain, spinal cord, and periphery, ultimately weakening the muscle. (medscape.com)
  • This expansion causes the features of some disorders to become more severe with each successive generation. (medlineplus.gov)
  • Genetic disorders result from new or inherited gene mutations . (amboss.com)
  • It is distinct from structural cardiac disorders such as coronary artery disease, valvular disorders, and congenital heart disorders. (msdmanuals.com)
  • Most single gene disorders can be investigated by prenatal diagnosis using DNA extracted from cells obtained from amniocentesis at 16-18 weeks' gestation or chorionic villus sampling (CVS) at about 10-12 weeks' gestation. (dorak.info)
  • In single gene disorders (as opposed to multifactorial-complex disorders), the mutation's population frequency is low, its penetrance is high, and the contribution of environment is lower with notable exceptions of PKU and few others. (dorak.info)
  • Next-generation sequencing of the whole exome is useful for testing for multiple candidate genes simultaneously or for discovering new, rare disorders. (medlink.com)
  • Whole exome sequencing is not suitable for detecting polynucleotide repeat disorders or large insertion/deletions. (medlink.com)
  • Huntington`s Disease (HD) is an autosomal dominant neurodegenerative disease affecting 4-to-7 per 100,000 individuals. (edubirdie.com)
  • In Huntington`s Disease, mutated protein aggregates within the neuronal cells of the caudate and putamen of the basal ganglia causing neuronal cell death. (edubirdie.com)
  • The purpose of these mice was to be able to study and understand repeat expansion which leads to Huntington`s Disease. (edubirdie.com)
  • The lab's current projects include: locating human sleep genes, uncovering the molecular mechanisms of human sleep regulation and human circadian rhythms, investigating mouse models with de/dys-myelinating disease, and classifying miRNAs that contribute to healthy myelin. (wikipedia.org)
  • Leber hereditary optic neuropathy (LHON), neurologically-associated retinitis pigmentosa (NARP), myoclonic epilepsy and ragged red-fiber disease (MERRF), maternally inherited myopathy and cardiomyopathy (MMC) (See Taylor & Turnbull, 2005 ). (dorak.info)
  • However, how lncRNAs contribute to the development of hereditary diseases in human is still mostly unknown. (biomedcentral.com)
  • This review is focused on hereditary diseases in the pathogenesis of which long non-coding RNAs play an important role. (biomedcentral.com)
  • Future research will help translate this knowledge into clinical practice which will not only lead to an increase in the diagnostic rate but also in the future can help with the development of etiotropic treatments for hereditary diseases. (biomedcentral.com)
  • TCF4 Triplet Repeat Expansion and Nuclear RNA Foci in Fuchs' Endothelial Corneal Dystrophy. (utswmed.org)
  • DNA segments with an abnormal number of these repeats are unstable and prone to errors during cell division. (medlineplus.gov)
  • An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. (lookformedical.com)
  • After leaving Millennium Pharmaceutical, from 1995- August 1997 Fu worked for Darwin Molecular Corporation for two years and took part in the search for mutations responsible for premature aging (Werner syndrome) and early onset Alzheimer's disease (presenilin 2). (wikipedia.org)
  • Occasionally, myotonic dystrophy is present at birth in children of mothers and, rarely, fathers with DM1 mutations. (msdmanuals.com)
  • These diseases are all caused by microsatellite mutations, where a microsatellite either has three bases, four bases, five bases, or six bases, and these mutations result in excess numbers of copy of these particular units. (hstalks.com)
  • What this slide shows is that these types of mutations can occur in various parts of the gene. (hstalks.com)
  • Humans with this autosomal dominant disease typically go to bed around 7:00 p.m. and wake up at 3:00 a.m. (wikipedia.org)
  • DM1 is a rare, progressive, genetic disease that affects skeletal, cardiac and smooth muscle. (tmcnet.com)
  • To combat these cardiac diseases, the AHA provides funding for biomedical research, advocates for public health policies and resources, and provides education training and tools to the greater community about heart health. (curefa.org)
  • The transition from stable to unstable occurred between 46 and 52 repeats. (wikipedia.org)
  • Together, these discoveries characterized the molecular basis of genetic "anticipation," the phenomenon of worsening severity in subsequent generations, as being due to unstable, expanded trinucleotide repeats. (wikipedia.org)
  • Analyzing pre-symptomatic tissue to gain insights into the molecular and mechanistic origins of late-onset degenerative trinucleotide repeat disease. (utswmed.org)
  • A trinucleotide repeat is a sequence of three DNA building blocks (nucleotides) that is repeated a number of times in a row. (medlineplus.gov)
  • Epigenetic regulation of gene expression encompasses mechanisms that allow regulating the expression of the genes without modification of the DNA sequence. (amboss.com)
  • Herein, we demonstrate molecular and physiological amelioration of the toxic effects of mutant RNA in the HSA(LR) mouse model of DM1 by systemic administration of peptide-linked morpholino (PPMO) antisense oligonucleotides bearing a CAG repeat sequence. (bvsalud.org)
  • Developing representative models of myotonic dystrophy in animals has been challenging due to instability of nucleotide repeat expansions, especially for DM2 which is characterized by nucleotide repeat expansions often greater than 5000 copies. (jci.org)
  • Orphan drug designation is granted by the FDA to drugs or biologics intended for treatment, prevention or diagnosis of a rare disease or condition that affects fewer than 200,000 people in the United States. (tmcnet.com)
  • Diagnosis of myotonic dystrophy is indicated by characteristic clinical findings, age at onset, and family history and is confirmed by DNA testing. (msdmanuals.com)
  • The differential diagnosis for the patient may include both genetic and non-genetic possibilities (for example, ataxia, dementia, and Parkinson disease). (medlink.com)
  • In a population of 250 individuals , there will be a total of 500 gene copies (all individuals carry two alleles of a gene ). (amboss.com)
  • Knock in mice models have more precise portrayal of the disease`s genotype as scientists are able to replace specific gene regions of the HD gene with human copies. (edubirdie.com)
  • Human genetics is the study of the human genome and the transmission of genes from one generation to the next. (amboss.com)
  • The focus of my talk is going to be on the genetics of these diseases, and I'll talk very little about the functional biology of these conditions. (hstalks.com)
  • Myotonic dystrophy is rare, autosomal dominant muscle disorder. (msdmanuals.com)
  • An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease. (lookformedical.com)
  • It is classed as a trinucleotide repeat disorder (Marcy et al, 1993) due to the fact that it results from an expanded CAG repeat which leads to a polyglutamine strand of variable length at the N-terminus (Walker, 2007). (edubirdie.com)
  • Furthermore, we believe that these results could signal the potential for the accumulation of exon 51 skipped transcript and dystrophin protein in muscle tissue with repeated doses of PGN-EDO51 in people living with DMD. (tipranks.com)
  • In hypermobility type of Ehlers-Danlos syndrome , haploinsufficiency (where one copy is unable to produce the protein in sufficient quantity) due to a 30-kb deletion of tenascin-X (TNXB) gene is responsible for the disease. (dorak.info)
  • His pioneering work provided key conceptual advances on the implication of synaptic protein dysfunction, and glial cells in DM1 brain disease. (ern-euro-nmd.eu)
  • Central nervous system (CNS) gene transfer by vectors like adeno-associated virus (AAV) overcome this barrier by allowing the bodies' own cells to produce the therapeutic protein, but previous studies using this method to target amyloid-ß have shown success only with truncated single chain antibodies (Abs) lacking an Fc domain. (bvsalud.org)
  • The protein encoded by this gene is a serine-threonine kinase that is closely related to other kinases that interact with members of the Rho family of small GTPases. (nih.gov)
  • Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
  • It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues. (lookformedical.com)
  • 2014). Although this study aims to find therapeutic benefit through nonallele-specific silencing of both the mutant and wild type huntingtin gene which codes for the huntingtin protein, it has been noted that the effects of nonallelle-specific silencing of the mutant htt still remains unknown. (edubirdie.com)
  • This expansion of CTG repeats causes toxic RNA to cluster in the nucleus, forming nuclear foci and altering the splicing of multiple proteins essential for normal cellular function. (tmcnet.com)
  • Expansions of CUG trinucleotide sequences in RNA transcripts provide the basis for toxic RNA gain-of-function that leads to detrimental changes in RNA metabolism. (bvsalud.org)
  • Antibody therapies for Alzheimer's Disease (AD) hold promise but have been limited by the inability of these proteins to migrate efficiently across the blood brain barrier (BBB). (bvsalud.org)
  • These findings suggest that CNS gene delivery of a silent anti-Aß scFv-IgG was well-tolerated, durably expressed and functional in a relevant disease model, demonstrating the potential of this modality for the treatment of Alzheimer's disease. (bvsalud.org)
  • Deficient Wnt Signaling and Synaptic Vulnerability in Alzheimer's Disease: Emerging Roles for the LRP6 Receptor. (ucl.ac.uk)
  • If expression of a trait requires only one copy of a gene (one allele). (msdmanuals.com)
  • In the rare disease erythropoietic protoporphyria , haploinsufficiency for ferrochelatase ( FECH ) contributes to the clinical phenotype but is not the only reason for the disease expression. (dorak.info)
  • CX3CR1 expression in lung epithelial cells may also have implications for other respiratory diseases such as asthma. (bvsalud.org)
  • May play a role in myocyte differentiation and survival by regulating the integrity of the nuclear envelope and the expression of muscle-specific genes. (nih.gov)
  • RNA-sequencing from DM1 and DM2 iPSC-derived cardiomyocytes revealed distinct misregulation of gene expression as well as differential aberrant splicing patterns. (jci.org)
  • 2009). Previous studies of utilising RNAi induced by short hairpin RNAs (shRNAs) to reduce expression of mutant htt have shown that there is a possibility of improving abnormalities relating to HD disease in a mouse model (S.Q Harper et al, 2005). (edubirdie.com)
  • Epigenetics broadly is a heritable genetic characteristic that is a cell-specific gene expression and regulation achieved by the interaction between DNA and transcriptional factors. (geneticeducation.co.in)
  • We showed previously that cytoplasmic release of mtDNA activates the cGAS STING TBK1 pathway resulting in interferon-stimulated gene (ISG) expression that promotes antiviral immunity4. (regenerativemedicine.net)
  • Here, we find that persistent mtDNA stress is not associated with basally activated NF-κB signalling or interferon gene expression typical of an acute antiviral response. (regenerativemedicine.net)
  • Symptoms and signs of myotonic dystrophy begin during adolescence or young adulthood and include myotonia (delayed relaxation after muscle contraction, which may be asymptomatic or described as muscle stiffness), weakness and wasting of distal limb muscles (especially in the hand) and facial muscles (ptosis is especially common), and cardiomyopathy. (msdmanuals.com)
  • It is also estimated that each human being is a carrier of around five recessive lethal genes and perhaps even more recessive disease genes, which may pose risk for the offspring of related individuals (such as cousin marriages). (dorak.info)
  • IPSC-derived cardiomyocytes from DM1 but not DM2 had aberrant splicing of known target genes and MBNL sequestration. (jci.org)
  • We extend our heartfelt appreciation to the participants in our Phase 1 HNV trial for their role in supporting our mission to develop transformative therapies for people living with DMD and other devastating neuromuscular diseases. (tipranks.com)
  • Receiving FDA orphan drug designation for DYNE-101 underscores the importance of bringing new treatment options to people living with DM1, a rare, devastating disease with no approved therapies. (tmcnet.com)
  • DM1 is estimated to affect more than 40,000 people in the United States and over 74,000 people in Europe, but there are currently no approved disease-modifying therapies. (dyne-tx.com)
  • The other key point of the slide is to show that these diseases are typically either neurological, neurodegenerative, or neuromuscular. (hstalks.com)
  • Myotonic dystrophy affects about 1/8000 in the general population. (msdmanuals.com)
  • Human Gene Therapy. (vub.be)
  • Mouse HD genes are 81% in similarity to that of the human HD gene when expressed at DNA level (Liou, 2010). (edubirdie.com)
  • Thousands of long non-coding RNA (lncRNA) genes are annotated in the human genome. (biomedcentral.com)
  • According to the GENCODE project one third of all human lncRNAs genes are primate-specific [ 4 ]. (biomedcentral.com)
  • Back in France, he joined Denis Furling's team as a post-doc and worked on DM1, another triplet expansion disease with intranuclear aggregates. (ern-euro-nmd.eu)
  • During her time at OSU, she cloned numerous genes important for nitrogen and sulfur metabolism in Neurospora. (wikipedia.org)
  • We herein demonstrated that circadian clock network in the intestines plays pivotal roles in skeletal metabolism such that the lack of Bmal1 gene in the intestines (Bmal1Int-/- mice) caused bone loss with bone resorption being activated and bone formation suppressed. (jci.org)
  • American Heart Association (AHA) - Founded in 1924, the AHA is the nation's largest and oldest organization dedicated to developing treatments and cures against heart disease and stroke. (curefa.org)
  • These diseases show familial aggregation but not strong familial segregation. (dorak.info)
  • Hemophilia Gene Therapy: The End of the Beginning? (vub.be)
  • NMDs are a group of diseases that affect any part of the nerve and muscle. (medscape.com)
  • His work and expertise have enabled him to publish more than 20 articles on DM1 and muscle diseases, to file a patent and to participate in several national and international collaborations with academic and industrial partners. (ern-euro-nmd.eu)