ALS / en ​ֱ, University of Cambridge researchers find mechanism behind neuron death in ALS and dementia /news/u-t-university-cambridge-researchers-find-mechanism-behind-neuron-death-als-and-dementia <span class="field field--name-title field--type-string field--label-hidden">​ֱ, University of Cambridge researchers find mechanism behind neuron death in ALS and dementia</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/2018-04-19-st.george-hyslop-resized.jpg?h=afdc3185&amp;itok=_h25lvlE 370w, /sites/default/files/styles/news_banner_740/public/2018-04-19-st.george-hyslop-resized.jpg?h=afdc3185&amp;itok=_9NaVM6j 740w, /sites/default/files/styles/news_banner_1110/public/2018-04-19-st.george-hyslop-resized.jpg?h=afdc3185&amp;itok=MmX0ksP6 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/2018-04-19-st.george-hyslop-resized.jpg?h=afdc3185&amp;itok=_h25lvlE" alt="Photo of Peter St George-Hyslop"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>noreen.rasbach</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2018-04-19T10:48:00-04:00" title="Thursday, April 19, 2018 - 10:48" class="datetime">Thu, 04/19/2018 - 10:48</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">Peter St George-Hyslop is director of the Tanz Centre for Research in Neurodegenerative Diseases and a professor in ֱ's Faculty of Medicine </div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/global-lens" hreflang="en">Global Lens</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/als" hreflang="en">ALS</a></div> <div class="field__item"><a href="/news/tags/faculty-medicine" hreflang="en">Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/global" hreflang="en">Global</a></div> <div class="field__item"><a href="/news/tags/research-innovation" hreflang="en">Research &amp; Innovation</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers at the University of Toronto and the University of Cambridge have identified the molecular mechanism that leads to the death of neurons in some types of ALS, or amyotrophic lateral sclerosis, and in a common form of frontotemporal dementia.</p> <p>They have also uncovered novel therapeutic targets for these currently incurable diseases.</p> <p>The journal <em>Cell</em> <a href="http://www.cell.com/cell/fulltext/S0092-8674(18)30388-X">published the findings on Thursday</a>.</p> <p>A common characteristic of ALS and frontotemporal dementia is the clumping of misfolded RNA-binding proteins, including a protein called FUS, in the brain and spinal cord. In nerve cells, FUS proteins normally change back and forth from small liquid droplets (resembling oil droplets in water) to small gels (like jelly).</p> <p>But in ALS and frontotemporal dementia, FUS proteins become permanently stuck as abnormally dense gels, trapping the RNA and making it unavailable for use. This damages nerve cells by blocking their ability to make the proteins needed for synaptic function and leads to the death of neurons in the brain and spinal cord.</p> <p>“This was a very exciting set of experiments where we were able to apply cutting-edge tools from physics, chemistry and neurobiology to understand how the FUS protein normally works in nerve cells, and how it goes wrong in motor neuron disease and dementia,” said&nbsp;<strong>Peter St George-Hyslop</strong>, director of the <a href="https://tanz.med.utoronto.ca/">Tanz Centre for Research in Neurodegenerative Diseases</a> and a professor in ֱ's Faculty of Medicine.</p> <h3><a href="/news/u-t-s-peter-st-george-hyslop-wins-leading-alzheimer-s-research-prize">Read more about Peter St George-Hyslop</a></h3> <p>In healthy neurons, the FUS protein condenses (from droplets to gel), captures RNA and transfers it to remote parts of the neuron involved in making connections (synapses) with other neurons. Here, the protein 'melts' and releases the RNA. The RNA then helps create new proteins in the synapses, which are essential for keeping the synapses working properly, especially during memory formation and learning.&nbsp;</p> <p>In frontotemporal dementia, the researchers found that defects in the chemical modification of FUS caused the abnormal gelling. In motor neuron disease, abnormal gelling arose from mutations in the FUS protein itself, which meant it was no longer able to change form.</p> <p>“These findings open up a new avenue of work to identify ways to prevent the abnormal gelling of FUS in motor neuron disease and dementia,” said St George-Hyslop, who is also a professor at the <a href="https://www.cimr.cam.ac.uk/">Institute for Medical Research</a> at the University of Cambridge.</p> <p>The scientists used human cells that resemble neurons, and neurons from frogs, to investigate the regulation of FUS from liquid droplets to small gels – and what makes that reversible process go awry. Potential therapeutic targets include the enzymes that regulate the chemical modification of FUS, and the molecular chaperones that facilitate FUS proteins to change form.</p> <p>These treatments would need to allow FUS to continue moving between safe reversible states (liquid droplets and reversible gels) but prevent FUS from dropping into the dense, irreversible gel states that cause disease.</p> <h3><a href="http://www.cell.com/cell/fulltext/S0092-8674(18)30388-X">Read the research in the journal <em>Cell</em></a></h3> <p>“For the past several years, evidence has been growing that understanding these phase transitions could significantly accelerate our ability to treat ALS,” said Dr. <strong>David Taylor</strong>, vice president, research at the <a href="https://www.als.ca/">ALS Society of Canada</a>. “The work advances our understanding of this biology and reveals potential molecular targets for exploration, which might someday lead to the development of ALS treatments.”</p> <p>Taylor notes that the research was possible in part through funding from the <a href="https://www.als.ca/tag/ice-bucket-challenge/">Ice Bucket Challenge</a> and the ALS Society of Canada’s partnership with <a href="https://braincanada.ca/">Brain Canada</a>, and he said the findings are an example of why continued investment in research funding is vital.</p> <p>The research was funded by the Canadian Institutes of Health Research, Wellcome Trust, European Research Council, Swiss National Science Foundation, and the ALS Society of Canada and Brain Canada (through the Canada Brain Research Fund, with support from Health Canada).</p> <p>&nbsp;</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Thu, 19 Apr 2018 14:48:00 +0000 noreen.rasbach 133725 at ֱ joins international ALS project /news/u-t-joins-international-als-project <span class="field field--name-title field--type-string field--label-hidden">ֱ joins international ALS project</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/2017-01-19-als.jpg?h=afdc3185&amp;itok=y_NTgfiK 370w, /sites/default/files/styles/news_banner_740/public/2017-01-19-als.jpg?h=afdc3185&amp;itok=iGgzTgSi 740w, /sites/default/files/styles/news_banner_1110/public/2017-01-19-als.jpg?h=afdc3185&amp;itok=VzaT6Hx_ 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/2017-01-19-als.jpg?h=afdc3185&amp;itok=y_NTgfiK" alt="Photo of the brain"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>ullahnor</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2017-01-19T11:05:02-05:00" title="Thursday, January 19, 2017 - 11:05" class="datetime">Thu, 01/19/2017 - 11:05</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item"> The project will map the DNA profiles of 15,000 people with ALS and create a global database of genetic information on the disease (photo by MV Maverick via Flickr)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/dan-haves" hreflang="en">Dan Haves</a></div> </div> <div class="field field--name-field-author-legacy field--type-string field--label-above"> <div class="field__label">Author legacy</div> <div class="field__item">Dan Haves</div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/als" hreflang="en">ALS</a></div> <div class="field__item"><a href="/news/tags/faculty-medicine" hreflang="en">Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/u-t" hreflang="en">ֱ</a></div> <div class="field__item"><a href="/news/tags/neurology" hreflang="en">Neurology</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><strong>Ekaterina Rogaeva</strong>, a professor of neurology at the University of Toronto's Faculty of Medicine,&nbsp;is joining an international team of researchers trying to determine why some people develop ALS.</p> <p>Known as Project MinE, the team helped discover the gene linked to ALS. It includes researchers in 17 nations, and now thanks to support from the ALS Society of Canada (ALS Canada), Canadian researchers have joined the team.</p> <p><img alt class="media-image attr__typeof__foaf:Image img__fid__3200 img__view_mode__media_original attr__format__media_original" src="/sites/default/files/2017-01-19-regaeva.jpg" style="width: 200px; height: 200px; margin: 10px; float: left;" typeof="foaf:Image">“About half of ALS heritability remains to be explained,” says Rogaeva (pictured left), who is also a researcher at the Tanz Centre for Research in Neurodegenerative Diseases.</p> <p>In an effort to accelerate the search for a cure, Project MinE plans to map the DNA profiles of 15,000 people with ALS along with a control group of 7,500 people and create a global database of genetic information on the disease. ­With this new data, the hope is that researchers around the world can better target ALS by understanding the genetic mutations that lead to disease.</p> <p>“Only together can we obtain sufficient power to analyze DNA samples from several thousand cases and controls&nbsp;so the ongoing whole genome sequencing of each MinE sample is critical,” say Rogaeva.</p> <p>ALS, or amyotrophic lateral sclerosis, is a neurodegenerative disease that gradually paralyzes the body. Most people who are diagnosed with ALS die within two to five years of diagnosis as there is currently no effective treatment or cure. One thousand Canadians are diagnosed with ALS each year.</p> <p>Project MinE will receive both the financial support of the ALS Canada and the scientific support of some of Canada’s leading ALS researchers. This is the first cross-Canada collaboration on ALS research and is one of the six projects funded by the ALS Ice Bucket Challenge.</p> <p>ALS Canada and its research team hope to contribute up to 1,000 DNA profiles to the MinE Project. They are currently seeking federal funding, which would also allow the stored DNA profiles of Canadians with ALS to be added to the database.</p> <p>“Having such a large sample set could improve understanding of the disease in order to provide the best medical advice to ALS carriers,” Rogaeva notes.</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Thu, 19 Jan 2017 16:05:02 +0000 ullahnor 103390 at Hope for ALS patients? Discovery of a gene's function offers clues /news/hope-als-patients-discovery-genes-function-offers-clues <span class="field field--name-title field--type-string field--label-hidden">Hope for ALS patients? Discovery of a gene's function offers clues </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>sgupta</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2014-07-28T09:28:13-04:00" title="Monday, July 28, 2014 - 09:28" class="datetime">Mon, 07/28/2014 - 09:28</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">Stephen Hawking (seen above at a NASA event in 2008), Canadian Sue Rodrigues and American baseball star Lou Gehrig are some of the most recognizable names of ALS patients (photo by NASA/Paul E. Alers via Flickr) </div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/katie-babcock" hreflang="en">Katie Babcock</a></div> <div class="field__item"><a href="/news/authors-reporters/heidi-singer" hreflang="en">Heidi Singer</a></div> <div class="field__item"><a href="/news/authors-reporters/heidi-singer" hreflang="en">Heidi Singer</a></div> </div> <div class="field field--name-field-author-legacy field--type-string field--label-above"> <div class="field__label">Author legacy</div> <div class="field__item">Katie Babcock and Heidi Singer</div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/top-stories" hreflang="en">Top Stories</a></div> <div class="field__item"><a href="/news/tags/medicine" hreflang="en">Medicine</a></div> <div class="field__item"><a href="/news/tags/health" hreflang="en">Health</a></div> <div class="field__item"><a href="/news/tags/als" hreflang="en">ALS</a></div> <div class="field__item"><a href="/news/tags/research" hreflang="en">Research</a></div> <div class="field__item"><a href="/news/tags/global" hreflang="en">Global</a></div> </div> <div class="field field--name-field-subheadline field--type-string-long field--label-above"> <div class="field__label">Subheadline</div> <div class="field__item">“This is an extremely important finding"</div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>ֱ researchers have found a missing link that helps to explain how ALS, one of the world’s most feared diseases, paralyses and ultimately kills its victims.</p> <p>The breakthrough is helping them trace a path to a treatment or even a cure.</p> <p>“ALS research has been taking baby steps for decades, but this has recently started changing to giant leaps,” said <strong>Karim Mekhail</strong>, an assistant professor in the Faculty of Medicine’s Department of Laboratory Medicine &amp; Pathobiology.&nbsp;</p> <p>“The disease is linked to a large number of genes, and previously, every time someone studied one of them, it took them off in a different direction. Nobody could figure out how they were all connected.”</p> <p>Mekhail and his team discovered the function of a crucial gene called PBP1 or ATAXIN2 that’s often missing in ALS, also known as Lou Gehrig’s Disease. Learning how this gene functions has helped them connect a lot of dots.</p> <p>“This is an extremely important finding that may help us to better understand and target the pathways involved in neurodegenerative disease,” said Dr.&nbsp;<strong>Lorne Zinman</strong>, an associate professor of medicine at ֱ and medical director of the ALS/Neuromuscular Clinic at Sunnybrook Health Sciences Centre. “The next step will be to determine if this finding is applicable to patients with ALS.”</p> <p>The key lies in a peculiarity of the human genome. It starts with the DNA, the blueprint that contains all our genetic information. The DNA passes its information to the RNA, which floats off to make proteins that help run our bodies. However, without ATAXIN2, the RNA fails to float away. It becomes glued to the DNA and forms RNA-DNA hybrids, said Mekhail. These hybrids gum up the works and stop other RNA from fully forming. Pieces of half-created RNA debris clutter the cell, and cause more hybrids.</p> <p><img alt src="/sites/default/files/2014-07-28-karim-mekhail.jpg" style="margin: 10px; width: 275px; float: right; height: 376px">“We think the debris and hybrids are on the same team in a never-ending Olympic relay race,” said Mekhail (pictured at right). “Over time there’s a vicious cycle building up. If we can find a way to disrupt that cycle, theoretically we can control or reverse the disease.”</p> <p>On that front, Mekhail made a very surprising discovery: reducing calories to the minimum necessary amount stops the hybrids from forming in cells missing ATAXIN2. He and his team are studying whether a simple, non-toxic dietary restriction could be used with ALS patients, especially in the early stages or for those at risk of ALS.</p> <p>Mekhail discovered the hybrids and missing genes in yeast cells and his results were published as the cover article for the<a href="http://www.cell.com/developmental-cell/current"> July 28 edition of the journal <em>Developmental Cell</em></a>. Now his team is replicating this research on tissue from ALS patients – with very encouraging preliminary results.</p> <p>"Within the next decade or two, I think there’s going to be a revolution in treatment for ALS and all kinds of brain disease,” he said. “These hybrids are going to play a role not just in ALS but in a lot of disease.”<br> &nbsp;</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> <div class="field field--name-field-picpath field--type-string field--label-above"> <div class="field__label">picpath</div> <div class="field__item">sites/default/files/2014-07-28-stephen-hawking-als-nasa.jpg</div> </div> Mon, 28 Jul 2014 13:28:13 +0000 sgupta 6399 at