{"id":121495,"date":"2024-11-03T06:53:45","date_gmt":"2024-11-02T23:53:45","guid":{"rendered":"https:\/\/hotvideos24.online\/?p=121495"},"modified":"2024-11-03T06:53:45","modified_gmt":"2024-11-02T23:53:45","slug":"polymer-therapy-shows-promise-against-huntingtons-disease","status":"publish","type":"post","link":"https:\/\/hotvideos24.online\/?p=121495","title":{"rendered":"Polymer Therapy Shows Promise Against Huntington\u2019s Disease"},"content":{"rendered":"<p> <script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js?client=ca-pub-3711241968723425\"\r\n     crossorigin=\"anonymous\"><\/script>\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-format=\"fluid\"\r\n     data-ad-layout-key=\"-fb+5w+4e-db+86\"\r\n     data-ad-client=\"ca-pub-3711241968723425\"\r\n     data-ad-slot=\"7910942971\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script><br \/>\n<\/p>\n<div>\n<p><strong>Summary: <\/strong>Scientists have developed a novel polymer-based therapy that could slow Huntington\u2019s disease progression by preventing harmful protein clumps in the brain. In a mouse model, this polymer therapy effectively halted cell death, improved neuron health, and enhanced motor function.<\/p>\n<p>The therapy, featuring peptide-like structures, disrupts toxic protein binding linked to cell damage and degeneration in Huntington\u2019s disease. It lasts longer in the body than traditional treatments, showing no significant side effects.<\/p>\n<p>Researchers hope this treatment could potentially be administered as a weekly injection to delay symptoms. This advance offers new hope for treating Huntington\u2019s disease, a currently incurable condition.<\/p>\n<p><strong>Key Facts:<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li>The polymer shields neurons by blocking harmful protein interactions associated with Huntington\u2019s disease.<\/li>\n<li>Treated mice showed improved brain cell health and exhibited more typical behavior.<\/li>\n<li>This therapy could potentially become a weekly treatment option to delay Huntington\u2019s symptoms.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>Northwestern University<\/p>\n<p><strong>Scientists at Northwestern and Case Western Reserve universities have developed the first polymer-based therapeutic for Huntington\u2019s disease, an incurable, debilitating illness that causes nerve cells to break down in the brain.<\/strong><\/p>\n<p>Patients with Huntington\u2019s disease have a genetic mutation that triggers proteins to misfold and clump together in the brain. These clumps interfere with cell function and eventually lead to cell death.<\/p>\n<figure class=\"wp-block-image size-full\"><picture fetchpriority=\"high\" decoding=\"async\" class=\"wp-image-105853\"><source type=\"image\/webp\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience.jpg.webp 1200w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-300x200.jpg.webp 300w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-770x513.jpg.webp 770w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-1155x770.jpg.webp 1155w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-370x247.jpg.webp 370w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-293x195.jpg.webp 293w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-150x100.jpg.webp 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/><img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"800\" src=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience.jpg\" alt=\"This shows a neuron.\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience.jpg 1200w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-300x200.jpg 300w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-770x513.jpg 770w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-1155x770.jpg 1155w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-370x247.jpg 370w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-293x195.jpg 293w, https:\/\/neurosciencenews.com\/files\/2024\/11\/polymer-therapy-huntingtons-neuroscience-150x100.jpg 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/> <\/picture><figcaption class=\"wp-element-caption\">Although the treatment needs further testing, the researchers imagine it potentially someday could be administered as a once-weekly injection to delay disease onset or reduce symptoms in patients with the genetic mutation. Credit: Neuroscience News<\/figcaption><\/figure>\n<p>As the disease progresses, patients lose the ability to talk, walk, swallow and concentrate. Most patients die within 10 to 20 years after symptoms first appear.<\/p>\n<p>The new treatment leverages peptide-brush polymers, which act as a shield to prevent proteins from binding to one another. In studies in mice, the treatment successfully rescued neurons to reverse symptoms. The treated mice also experienced no significant side effects, confirming the therapy is nontoxic and well tolerated.<\/p>\n<p>Although the treatment needs further testing, the researchers imagine it potentially someday could be administered as a once-weekly injection to delay disease onset or reduce symptoms in patients with the genetic mutation.<\/p>\n<p>The study will be published on Friday (Nov. 1), in the journal\u00a0<em>Science Advances.<\/em><\/p>\n<p>\u201cHuntington\u2019s is a horrific, insidious disease,\u201d said Northwestern\u2019s\u00a0Nathan Gianneschi, who led the polymer therapeutic development.<\/p>\n<p>\u201cIf you have this genetic mutation, you will get Huntington\u2019s disease. It\u2019s unavoidable; there\u2019s no way out. There is no real treatment for stopping or reversing the disease, and there is no cure.<\/p>\n<p>\u201cThese patients really need help. So, we started thinking about a new way to address this disease. The misfolded proteins interact and aggregate. We\u2019ve developed a polymer that can fight those interactions.\u201d<\/p>\n<p>Gianneschi is the Jacob and Rosaline Cohn Professor of Chemistry at Northwestern\u2019s\u00a0Weinberg College of Arts and Sciences\u00a0and professor of materials science and engineering and biomedical engineering at Northwestern\u2019s\u00a0McCormick School of Engineering\u00a0as well as in Pharmacology at Feinberg School of Medicine. He also is a member of the\u00a0International Institute of Nanotechnology.<\/p>\n<p>Gianneschi co-led the study with Xin Qi, the Jeanette M. and Joseph S. Silber Professor of Brain Sciences and co-director of the Center for Mitochondrial Research and Therapeutics, at Case Western Reserve University.<\/p>\n<p><strong>Promising peptide<\/strong><\/p>\n<p>The new study builds on\u00a0previous work from Qi\u2019s laboratory\u00a0at Case Western Reserve. In 2016, Qi and her team identified a protein (valosin-containing protein or VCP)\u00a0that abnormally binds to the mutant Huntington protein, causing protein aggregates.<\/p>\n<p>These aggregates accumulate within a cell\u2019s mitochondria, an organelle that generates the energy needed to power a cell\u2019s biochemical reactions. Without functioning mitochondria, the cells become dysfunctional and then self-destruct.\u00a0<\/p>\n<p>As part of that study, Qi also uncovered a naturally occurring peptide that disrupts the interaction between the VCP and the mutant Huntington protein. In cells exposed to the peptide, both the VCP and mutant Huntington protein bound to the peptide \u2014 instead of each other.<\/p>\n<p>\u201cQi\u2019s team identified a peptide that comes from the mutant protein itself and basically controls the protein-protein interface,\u201d Gianneschi said. \u201cThat peptide inhibited mitochondrial death, so it showed promise.\u201d<\/p>\n<p><strong>Pulling apart proteins like Velcro<\/strong><\/p>\n<p>But the peptide, by itself, faced several limitations. Because they are easily broken down by enzymes, peptides have a short lifespan in the body and often have difficulty effectively entering cells.<\/p>\n<p>For the peptide to inhibit Huntington\u2019s disease, it needs to cross the blood-brain barrier in large enough quantities to prevent large-scale protein aggregation.\u00a0<\/p>\n<p>\u201cThe peptide has a very small footprint with respect to the protein interfaces,\u201d Gianneschi said.<\/p>\n<p>\u201cThe proteins stick to each other like Velcro. In this analogy, one protein has hooks and the other has loops. The peptide, on its own, is like trying to undo a patch of Velcro by pulling apart one hook and loop at a time.<\/p>\n<p>\u201cBy the time you get to the bottom of the patch, the top has already come back together and resealed. We needed something big enough to disrupt the entire interface.\u201d<\/p>\n<p>To overcome these obstacles, Gianneschi and his team developed a biocompatible polymer that displays multiple copies of the active peptide. The new structure has a polymer backbone with peptides attached like branches.<\/p>\n<p>Not only does the structure protect the peptides from destructive enzymes, it also helps them cross the blood-brain barrier and enter cells.<\/p>\n<p><strong>Experimental results<\/strong><\/p>\n<p>In laboratory experiments, Gianneschi and his team injected the protein-like polymer into a mouse model of Huntington\u2019s disease. The polymers stayed in the body 2,000 times longer than traditional peptides.<\/p>\n<p>In biochemical and neuropathological examinations, the researchers found the treatment prevented mitochondrial fragmentation to preserve the health of brain cells. According to Gianneschi, the mice with Huntington\u2019s disease also lived longer and behaved more like normal mice.<\/p>\n<p>\u201cIn one study, the mice are examined in an open field test,\u201d Gianneschi said.<\/p>\n<p>\u201cIn the animals with Huntington\u2019s, as the disease progresses, they stay along the edges of the box. Whereas normal animals cross back and forth to explore the space. The treated animals with Huntington\u2019s disease started to do the same thing. It\u2019s quite compelling when you see animals behave more normally than they would otherwise.\u201d<\/p>\n<p>Next, Gianneschi will continue to optimize the polymer, with plans to explore its use in other neurodegenerative diseases.<\/p>\n<p>\u201cMy childhood friend was diagnosed with Huntington\u2019s at age 18 through a genetic test,\u201d Gianneschi said.<\/p>\n<p>\u201cHe\u2019s now in an assisted living facility because he needs 24-hour, full-time care. I remain highly motivated \u2014 both personally and scientifically \u2014\u00a0to continue traveling down the path.\u201d<\/p>\n<p><strong>Funding: <\/strong>The study, \u201cProteomimetic polymer blocks mitochondrial damage, rescues Huntington\u2019s neurons and slows onset of neuropathy in vivo,\u201d was supported by the International Institute of Nanotechnology Convergence Science Medicine Institute grant, National Institutes of Health (award numbers 1F31AG076334, R01AG065240, R01NS115903, R01AG076051 and RF1AG074346.)<\/p>\n<h2 class=\"wp-block-heading\">About this Huntington\u2019s disease research news<\/h2>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"http:\/\/neurosciencenews.com\/cdn-cgi\/l\/email-protection#26474b474842474b4966484954524e5143555243544808434253\" target=\"_blank\" rel=\"noreferrer noopener\">Amanda Morris<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/northwestern.edu\" target=\"_blank\" rel=\"noreferrer noopener\">Northwestern University<\/a><br \/><strong>Contact: <\/strong>Amanda Morris \u2013 Northwestern University<br \/><strong>Image: <\/strong>The image is credited to Neuroscience News<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Original Research: <\/strong>Open access.<br \/>\u201c<a href=\"https:\/\/www.science.org\/doi\/10.1126\/sciadv.ado8307\" target=\"_blank\" rel=\"noreferrer noopener\">Proteomimetic Polymer Blocks Mitochondrial Damage, Rescues Huntington\u2019s Neurons, and Slows Onset of Neuropathology In Vivo<\/a>\u201d by Nathan Gianneschi et al. <em>Science Advances<\/em><\/p>\n<hr class=\"wp-block-separator has-text-color has-pale-cyan-blue-color has-alpha-channel-opacity has-pale-cyan-blue-background-color has-background\"\/>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>Proteomimetic Polymer Blocks Mitochondrial Damage, Rescues Huntington\u2019s Neurons, and Slows Onset of Neuropathology In Vivo<\/strong><\/p>\n<p>Recently, it has been shown that blocking the binding of valosin-containing protein (VCP) to mutant huntingtin (mtHtt) can prevent neuronal mitochondrial autophagy in Huntington\u2019s disease (HD) models.<\/p>\n<p>Herein, we describe the development and efficacy of a protein-like polymer (PLP) for inhibiting this interaction in cellular and in vivo models of HD.<\/p>\n<p>PLPs exhibit bioactivity in HD mouse striatal cells by successfully inhibiting mitochondrial destruction. PLP is notably resilient to in vitro enzyme, serum, and liver microsome stability assays, which render analogous control oligopeptides ineffective.<\/p>\n<p>PLP demonstrates a 2000-fold increase in circulation half-life compared to peptides, exhibiting an elimination half-life of 152 hours.<\/p>\n<p>In vivo efficacy studies in HD transgenic mice (R6\/2) confirm the superior bioactivity of PLP compared to free peptide through behavioral and neuropathological analyses.<\/p>\n<p>PLP functions by preventing pathologic VCP\/mtHtt binding in HD animal models; exhibits enhanced efficacy over the parent, free peptide; and implicates the PLP as a platform with potential for translational central nervous system therapeutics.<\/p>\n<p> <!-- Form created by Optin Forms plugin by WPKube: create beautiful optin forms with ease! --> <!-- https:\/\/wpkube.com\/ --><!--optinforms-form5-container--> <!-- \/ Optin Forms --> <\/div>\n<p><script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js?client=ca-pub-3711241968723425\"\r\n     crossorigin=\"anonymous\"><\/script>\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-format=\"fluid\"\r\n     data-ad-layout-key=\"-fb+5w+4e-db+86\"\r\n     data-ad-client=\"ca-pub-3711241968723425\"\r\n     data-ad-slot=\"7910942971\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script><br \/>\n<br \/><div data-type=\"_mgwidget\" data-widget-id=\"1660802\">\r\n<\/div>\r\n<script>(function(w,q){w[q]=w[q]||[];w[q].push([\"_mgc.load\"])})(window,\"_mgq\");\r\n<\/script>\r\n<br \/>\n<br \/><a href=\"https:\/\/neurosciencenews.com\/polymer-huntingtons-disease-27967\/\">Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Summary: Scientists have developed a novel polymer-based therapy that could slow Huntington\u2019s disease progression by preventing harmful protein clumps in the brain. 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