{"id":213603,"date":"2026-06-02T08:00:00","date_gmt":"2026-06-02T12:00:00","guid":{"rendered":"https:\/\/inrs.ca\/?p=213603"},"modified":"2026-06-01T15:22:20","modified_gmt":"2026-06-01T19:22:20","slug":"amyotrophic-lateral-sclerosis-a-discovery-that-changes-our-understanding-of-the-disease","status":"publish","type":"post","link":"https:\/\/inrs.ca\/en\/news\/amyotrophic-lateral-sclerosis-a-discovery-that-changes-our-understanding-of-the-disease\/","title":{"rendered":"Amyotrophic Lateral Sclerosis: A Discovery\u00a0That Changes Our Understanding of the Disease\u00a0"},"content":{"rendered":"\n<p class=\"has-large-font-size wp-block-paragraph\"><strong>An INRS research team&nbsp;identifies&nbsp;an early and potentially reversible mechanism that could help protect brain cells<\/strong>.<\/p>\n\n\n    \n<div class=\"wp-block full-width-image \">\n    <div class=\"image-ctn\">\n        <img decoding=\"async\" src=\"https:\/\/inrs.ca\/wp-content\/uploads\/Kassen-Patten-AFSB-INRS.jpg\" alt=\"\" \/>\n    <\/div>\n    <p>Professor Kessen Patten<\/p>\n<\/div>\n\n\n<p class=\"has-drop-cap wp-block-paragraph\">In Canada, between 3,000 and 4,000 people are living with amyotrophic lateral sclerosis (ALS), a disease that&nbsp;remains&nbsp;incurable. ALS is best known for the degeneration of motor neurons, which&nbsp;are responsible for&nbsp;controlling movement. Their progressive loss,&nbsp;particularly in the motor cortex and spinal cord,&nbsp;leads to rapid paralysis, with a life expectancy of 2 to 5 years after diagnosis.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This serious neurodegenerative disease causes a gradual loss of muscle control, typically leading to paralysis within a few years. Until now, research has primarily focused on brain regions directly involved in movement.&nbsp;However, a new study led by&nbsp;Professor&nbsp;<a href=\"https:\/\/inrs.ca\/en\/research\/professors\/kessen-patten\/\" target=\"_blank\" rel=\"noreferrer noopener\">Kessen Patten<\/a>, at the&nbsp;Institut&nbsp;national de la recherche&nbsp;scientifique&nbsp;(INRS)&nbsp;and holder of the&nbsp;<a href=\"https:\/\/inrs.ca\/la-recherche\/chaires-groupes-et-reseaux-de-recherche\/repertoire-des-chaires-groupes-et-reseaux-de-recherche\/chaire-philanthropique-anna-sforza-djoukhadjian\/\" target=\"_blank\" rel=\"noreferrer noopener\">Anna Sforza Djoukhadjian Research Chair in Amyotrophic Lateral Sclerosis<\/a>, proposes a major shift in perspective: the disease may begin elsewhere in the brain,&nbsp;and well before the first visible symptoms appear.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Published in the journal&nbsp;<em>Brain<\/em>, the&nbsp;<a href=\"https:\/\/doi.org\/10.1093\/brain\/awag092\" target=\"_blank\" rel=\"noreferrer noopener\">study<\/a>,&nbsp;obtained from zebrafish models and human clinical samples,&nbsp;sheds new light on early brain changes associated with ALS. These findings&nbsp;provide&nbsp;new insight into the disease and may help inform future efforts toward earlier diagnosis and therapeutic development, as&nbsp;nearly 1,000&nbsp;new cases are diagnosed each year in Canada.&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-the-cerebellum-a-long-overlooked-key-player-nbsp\">The Cerebellum: A Long-Overlooked Key Player&nbsp;<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Rather than focusing solely on motor regions, researchers turned their attention to the&nbsp;cerebellum,&nbsp;a brain region associated with balance and&nbsp;coordination, but&nbsp;long underestimated in ALS.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In the most common genetic form of the disease (linked to the&nbsp;<em>C9orf72<\/em>&nbsp;gene)&nbsp;in zebrafish, they&nbsp;observed&nbsp;early cerebellar atrophy, characterized by the loss of two essential types of neurons:&nbsp;Purkinje cells&nbsp;and&nbsp;granule cells,&nbsp;well before the onset of motor symptoms.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Zebrafish are widely used in biomedical research because they share many genetic and cellular mechanisms with humans, making them a valuable model for studying neurodegenerative diseases such as ALS.&nbsp;<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\">\u201cOur results show that ALS is not limited to motor regions of the brain. Significant changes occur elsewhere, long before symptoms appear, which profoundly changes our understanding of the disease.\u201d&nbsp;<\/p>\n<cite>Dr.&nbsp;<strong>Kessen Patten,<\/strong><em>&nbsp;<\/em>Professor&nbsp;of Genetics and Neurodegenerative Diseases at INRS and lead author of the study.&nbsp;<\/cite><\/blockquote>\n\n\n\n<p class=\"wp-block-paragraph\">To understand this phenomenon, the team used an advanced technology that allows researchers&nbsp;to analyze gene activity in individual cells. This approach led to the identification of a key issue: decreased activity of the&nbsp;<em>paics&nbsp;<\/em>gene, which produces an enzyme essential for the synthesis of&nbsp;purines, molecules&nbsp;required&nbsp;to build and repair DNA.&nbsp;<\/p>\n\n\n\n<figure data-wp-context=\"{&quot;imageId&quot;:&quot;6a97adf428b16&quot;}\" data-wp-interactive=\"core\/image\" data-wp-key=\"6a97adf428b16\" class=\"wp-block-image size-large wp-lightbox-container\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"368\" data-wp-class--hide=\"state.isContentHidden\" data-wp-class--show=\"state.isContentVisible\" data-wp-init=\"callbacks.setButtonStyles\" data-wp-on--click=\"actions.showLightbox\" data-wp-on--load=\"callbacks.setButtonStyles\" data-wp-on--pointerdown=\"actions.preloadImage\" data-wp-on--pointerenter=\"actions.preloadImageWithDelay\" data-wp-on--pointerleave=\"actions.cancelPreload\" data-wp-on-window--resize=\"callbacks.setButtonStyles\" src=\"https:\/\/inrs.ca\/wp-content\/uploads\/Patten-AFSB-INRS-Lab-illust-1024x368.jpg\" alt=\"\" class=\"wp-image-213625\" srcset=\"https:\/\/inrs.ca\/wp-content\/uploads\/Patten-AFSB-INRS-Lab-illust-1024x368.jpg 1024w, https:\/\/inrs.ca\/wp-content\/uploads\/Patten-AFSB-INRS-Lab-illust-300x108.jpg 300w, https:\/\/inrs.ca\/wp-content\/uploads\/Patten-AFSB-INRS-Lab-illust-768x276.jpg 768w, https:\/\/inrs.ca\/wp-content\/uploads\/Patten-AFSB-INRS-Lab-illust.jpg 1414w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><button\n\t\t\tclass=\"lightbox-trigger\"\n\t\t\ttype=\"button\"\n\t\t\taria-haspopup=\"dialog\"\n\t\t\tdata-wp-bind--aria-label=\"state.thisImage.triggerButtonAriaLabel\"\n\t\t\tdata-wp-init=\"callbacks.initTriggerButton\"\n\t\t\tdata-wp-on--click=\"actions.showLightbox\"\n\t\t\tdata-wp-style--right=\"state.thisImage.buttonRight\"\n\t\t\tdata-wp-style--top=\"state.thisImage.buttonTop\"\n\t\t>\n\t\t\t<svg xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"12\" height=\"12\" fill=\"none\" viewBox=\"0 0 12 12\">\n\t\t\t\t<path fill=\"#fff\" d=\"M2 0a2 2 0 0 0-2 2v2h1.5V2a.5.5 0 0 1 .5-.5h2V0H2Zm2 10.5H2a.5.5 0 0 1-.5-.5V8H0v2a2 2 0 0 0 2 2h2v-1.5ZM8 12v-1.5h2a.5.5 0 0 0 .5-.5V8H12v2a2 2 0 0 1-2 2H8Zm2-12a2 2 0 0 1 2 2v2h-1.5V2a.5.5 0 0 0-.5-.5H8V0h2Z\" \/>\n\t\t\t<\/svg>\n\t\t<\/button><figcaption class=\"wp-element-caption\">Immunohistological\u00a0analysis of human post-mortem cerebellar sections. Cr\u00e9dit : Kessen Patten<\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Without these molecules, cells become unable to repair the DNA damage that naturally occurs. This damage accumulates progressively, leading to the failure of repair mechanisms and, ultimately, to&nbsp;neuron death.&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-a-reversible-mechanism-offering-new-perspectives\">A Reversible Mechanism, Offering New Perspectives<\/h2>\n\n\n\n<figure data-wp-context=\"{&quot;imageId&quot;:&quot;6a97adf429562&quot;}\" data-wp-interactive=\"core\/image\" data-wp-key=\"6a97adf429562\" class=\"wp-block-image alignright size-large is-resized is-style-rounded wp-lightbox-container\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"1015\" data-wp-class--hide=\"state.isContentHidden\" data-wp-class--show=\"state.isContentVisible\" data-wp-init=\"callbacks.setButtonStyles\" data-wp-on--click=\"actions.showLightbox\" data-wp-on--load=\"callbacks.setButtonStyles\" data-wp-on--pointerdown=\"actions.preloadImage\" data-wp-on--pointerenter=\"actions.preloadImageWithDelay\" data-wp-on--pointerleave=\"actions.cancelPreload\" data-wp-on-window--resize=\"callbacks.setButtonStyles\" src=\"https:\/\/inrs.ca\/wp-content\/uploads\/IMG_1892_1-1024x1015.jpg\" alt=\"\" class=\"wp-image-213607\" style=\"width:260px\" srcset=\"https:\/\/inrs.ca\/wp-content\/uploads\/IMG_1892_1-1024x1015.jpg 1024w, https:\/\/inrs.ca\/wp-content\/uploads\/IMG_1892_1-300x297.jpg 300w, https:\/\/inrs.ca\/wp-content\/uploads\/IMG_1892_1-150x150.jpg 150w, https:\/\/inrs.ca\/wp-content\/uploads\/IMG_1892_1-768x761.jpg 768w, https:\/\/inrs.ca\/wp-content\/uploads\/IMG_1892_1.jpg 1448w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><button\n\t\t\tclass=\"lightbox-trigger\"\n\t\t\ttype=\"button\"\n\t\t\taria-haspopup=\"dialog\"\n\t\t\tdata-wp-bind--aria-label=\"state.thisImage.triggerButtonAriaLabel\"\n\t\t\tdata-wp-init=\"callbacks.initTriggerButton\"\n\t\t\tdata-wp-on--click=\"actions.showLightbox\"\n\t\t\tdata-wp-style--right=\"state.thisImage.buttonRight\"\n\t\t\tdata-wp-style--top=\"state.thisImage.buttonTop\"\n\t\t>\n\t\t\t<svg xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"12\" height=\"12\" fill=\"none\" viewBox=\"0 0 12 12\">\n\t\t\t\t<path fill=\"#fff\" d=\"M2 0a2 2 0 0 0-2 2v2h1.5V2a.5.5 0 0 1 .5-.5h2V0H2Zm2 10.5H2a.5.5 0 0 1-.5-.5V8H0v2a2 2 0 0 0 2 2h2v-1.5ZM8 12v-1.5h2a.5.5 0 0 0 .5-.5V8H12v2a2 2 0 0 1-2 2H8Zm2-12a2 2 0 0 1 2 2v2h-1.5V2a.5.5 0 0 0-.5-.5H8V0h2Z\" \/>\n\t\t\t<\/svg>\n\t\t<\/button><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">When&nbsp;<em>paics<\/em>&nbsp;gene activity decreases, DNA damage accumulates and cellular repair systems eventually fail, leading to cell degeneration.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\">\u201cWe were able to establish a direct link between a defect in the production of purines and the accumulation of DNA damage in brain cells, which helps us better understand the origin of their degeneration.\u201d&nbsp;&nbsp;<\/p>\n<cite><strong>Jaskaran Singh<\/strong>, Doctoral student at INRS and first author of the study&nbsp;<\/cite><\/blockquote>\n\n\n\n<p class=\"wp-block-paragraph\">One of the most promising findings is that this mechanism may be&nbsp;reversible.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In an experimental model, researchers were able to restore&nbsp;<em>paics&nbsp;<\/em>gene activity. As a result, DNA damage decreased, neurons survived, and disease progression was halted at the cellular level.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">For people living with ALS and their families, these findings&nbsp;represent&nbsp;an important step&nbsp;forward. By showing that restoring&nbsp;<em>paics<\/em>&nbsp;function can reduce DNA damage and help protect neurons in experimental models, the study points to a promising pathway that could be explored in future therapeutic research. While further studies are needed, this work contributes to ongoing efforts to better understand the disease and its progression.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"h-about-the-study-nbsp-nbsp\">About the study&nbsp;&nbsp;<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Jaskaran Singh, L\u00e9a&nbsp;Lescouz\u00e8res, Charlotte Zaouter, Mathilde Chaineau, Ghazal Haghi, Thomas M Durcan,&nbsp;Shunmoogum&nbsp;A Patten, PAICS mediates DNA damage and cerebellar neuronal loss in C9orf72 amyotrophic lateral sclerosis, Brain,&nbsp;2026;,&nbsp;awag092,&nbsp;<a href=\"https:\/\/doi.org\/10.1093\/brain\/awag092\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/doi.org\/10.1093\/brain\/awag092<\/a>&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This work was made possible through funding from Brain Canada,&nbsp;Cermo-FC, the Armand-Frappier Foundation, the Fonds de recherche du Qu\u00e9bec \u2013 Sant\u00e9, the Anna Sforza&nbsp;Djoukhadjian&nbsp;Research Chair in Amyotrophic Lateral Sclerosis of the Armand-Frappier Foundation, the Natural Sciences and Engineering Research Council of Canada, and the Canadian Institutes of Health Research.&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>An INRS research team identifies an early and potentially reversible mechanism that could help protect brain cells.<\/p>\n","protected":false},"author":4,"featured_media":213609,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[688],"tags":[],"sectors":[],"class_list":["post-213603","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-innover-a-linrs-en"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v26.1 (Yoast SEO v28.3) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Amyotrophic Lateral Sclerosis: A Discovery\u00a0That Changes Our Understanding of the Disease\u00a0 | INRS<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/inrs.ca\/en\/news\/amyotrophic-lateral-sclerosis-a-discovery-that-changes-our-understanding-of-the-disease\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Amyotrophic Lateral Sclerosis: A Discovery\u00a0That Changes Our Understanding of the Disease\u00a0\" \/>\n<meta property=\"og:description\" content=\"An INRS research team identifies an early and potentially reversible mechanism that could help protect brain cells.\" \/>\n<meta property=\"og:url\" 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