{"id":12365,"date":"2019-10-01T10:15:04","date_gmt":"2019-10-01T16:15:04","guid":{"rendered":"http:\/\/canadianglycomics.ca\/?p=12365"},"modified":"2019-10-01T11:24:14","modified_gmt":"2019-10-01T17:24:14","slug":"tracing-the-path-of-parkinsons-disease","status":"publish","type":"post","link":"https:\/\/canadianglycomics.ca\/fr\/tracing-the-path-of-parkinsons-disease\/","title":{"rendered":"Tracing the path of Parkinson\u2019s disease"},"content":{"rendered":"

Like\na GPS, this tracer could identify and monitor the disease progression<\/p>\n\n\n\n

\"\"
Dr. Chris Phenix, GlycoNet Investigator and Assistant Professor from the University of Saskatchewan, is developing a PET tracer to trace the path of Parkinson’s disease (Photo: Saskatchewan Health Research Fund )<\/figcaption><\/figure>\n\n\n\n

by\nAli Chou<\/p>\n\n\n\n

When\nwe think we are healthy, we may overlook minute symptoms like anxiety or\nlight-headedness. But those can in fact be symptoms of Parkinson\u2019s disease (PD).\nWhile Parkinson\u2019s disease is more commonly associated with motor symptoms like tremor,\nin many cases, and often prior to a diagnosis, patients may experience non-motor\nsymptoms such as mood or cognitive disorders. Some people might think they have\nmood swings because they are experiencing stress at work, for example. Since\nsome of these issues are not automatically associated with more severe health\nproblems, they can easily be written off, which can get in the way of a timely\nPD diagnosis. <\/p>\n\n\n\n

What if there was a real-time tracking system that could monitor for early onset of aggressive disease, even before severe symptoms appeared? A team of GlycoNet Investigators Drs. Christopher Phenix<\/a>, Rebecca Davis<\/a>, Justin Hicks<\/a>, Darrel Mousseau<\/a>, et David Palmer<\/a> are looking to develop just that. <\/p>\n\n\n\n

Specifically,\nthe team is working on an injectable tracking device\u2014a positron emission\ntomography (PET) tracer\u2014that can tell in real-time if a patient is at risk for\nearly onset of PD.  PET requires the\ninjection of small amounts of a radioactive tracer to create pictures that\nmeasure biochemical activity in the living brain.  Due to its unrivaled power to image brain\nactivity, PET is already used in clinics to reveal various neurological\ndisorders. <\/p>\n\n\n\n

While\nthe causes for PD are not yet fully understood, one of the earliest changes in\nthe brain is the aggregation of insoluble proteins. This accumulation is\nheavily correlated with the dysfunction of an enzyme\u2014\u03b2-glucocerebrosidase (GCase).<\/p>\n\n\n\n

\u201cPatients\nwho have Parkinson\u2019s disease are known to have lower activities of GCase in the brain,\u201d says Phenix. \u201cThis\nenzyme normally functions by recycling cell wastes and metabolites through\nremoval of sugars from fats found in cell membranes. If there is an\ninsufficient amount of GCase, wastes would build up and eventually damage brain\ncells, resulting in more severe symptoms of Parkinson\u2019s disease earlier on. We\nare designing a PET tracer to monitor this enzyme\u2019s activity.\u201d<\/p>\n\n\n\n

Unlike\nother PET tracers for PD, which give a snapshot of glucose (sugar) metabolism\nor dopamine receptor activity in the brain, the version proposed by the\nGlycoNet researchers would track the activity of GCase. This could give a better indication of early\nbiochemical changes in the brain of PD patients.<\/p>\n\n\n\n

\u201cExisting\ndiagnostic PET tracers that monitor dopamine receptors show the areas where\nbrain neurons are dead. At this stage, there is already irreversible damage to\nthose areas of the brain,\u201d explains Phenix. \u201cWhereas tracing GCase would\nproduce a PET image showing the extent of GCase dysfunction. Recent evidence\nsuggests that this phenomenon occurs at a much earlier stage in Parkinson\u2019s\ndisease.\u201d <\/p>\n\n\n\n

In\nmedicine, earlier is always better. Early diagnoses enable patients to receive\nappropriate care and treatment sooner.<\/p>\n\n\n\n

However,\ndesigning a radioactive tracer that can image GCase is no easy task. It\ninvolves several complex steps. First, investigators need to design,\nsynthesize, and optimize radio-labeled molecules that bind to GCase\u2014usually\nthis step involves multiple iterations of improvement to tease out a set of\nbest candidate molecules. Second, the team conducts exhaustive testing in neuronal\ncells and animal models before the molecules can be put through clinical trials\nin humans. Prior to moving into a full scale clinical trial, in-patient studies\nare necessary to confirm that the tracer can image GCase in humans. The team\nneeds to be made up of experts from different fields in order for the process\nto move along seamlessly.<\/p>\n\n\n\n

\u201cIt\nis much more efficient to have various experts working within a collaborative\nteam throughout the project,\u201d says Phenix. \u201cDr. Rebecca Davis (University of\nManitoba), for example, uses computers to identify lead compounds that will\nbind to GCase; she looks at the enzyme\u2019s structure in 3D and helps us optimize\nthe affinity of the compound to our target. Based on her advice, we then\nprepare the compounds she has identified and test them in the lab.\u201d <\/p>\n\n\n\n

Phenix\nis also collaborating with two other Investigators from University of\nSaskatchewan and one from the Lawson Health Research Institute in Ontario. Dr. Palmer\n(University of Saskatchewan) is helping the team synthesize and identify new\ncompounds that efficiently target GCase. Dr. Mousseau (University of\nSaskatchewan) provides expertise in neurobiology to evaluate the radiotracers\nin cells and animals, while Dr. Hicks (Lawson Health Research Institute)\nleverages his knowledge of radiotracers in the brain to inform the team\u2019s next\nsteps.  <\/p>\n\n\n\n

At\nthis stage, the multidisciplinary team has developed synthetic routes to efficiently\nprepare a variety of radio-labeled derivatives and have identified promising\ncompounds based on experiments using neuronal cells. The group is moving\ntowards preclinical studies to ensure that the radioactive compounds can trace\nGCase in living animals properly. \u201cSelectivity,\u201d or the act of binding only to\nthe target enzyme, will be validated in living animals during this phase of the\nresearch process.<\/p>\n\n\n\n

\u201cSelectivity\nof the tracer is absolutely critical,\u201d say Phenix, \u201cthere are over ten thousand\nother proteins in the body, and there are three other enzymes that are very\nsimilar to GCase. We need to make sure our tracer only binds to GCase, so that\nthe PET image would show the accurate trace.\u201d<\/p>\n\n\n\n

In\naddition to being used as a diagnostic aid for PD, the PET tracer could\npotentially facilitate the development of new PD therapeutics. \u201cThere are\nseveral companies developing therapeutics that aim to increase GCase activity.\nOur tracer could help guide their development\u2014by tracing GCase, we can tell\nwhich drug candidates are most effective in increasing the enzyme\u2019s activity,\u201d\nsays Phenix. <\/p>\n\n\n\n

If\nPhenix and his collaborators are successful in developing a PET tracer, the\nteam believes this can benefit neurologists, researchers, and patients by using\nthe tracer as a tool to understand the biology of PD and potentially as a\ndiagnostic aid. <\/p>\n\n\n\n

\u201cThere\nare certainly examples where it can be difficult to distinguish Parkinson\u2019s\ndisease from related disease, such as dementia with Lewy bodies (aggregation of\ninsoluble proteins). We hope that our tracer could become a diagnostic aid to\nconfirm and identify the disease earlier, improving patient\u2019s quality of life,\u201d\nsays Phenix.   <\/p>","protected":false},"excerpt":{"rendered":"

Like a GPS, this tracer could identify and monitor the disease progression<\/p>","protected":false},"author":2,"featured_media":12366,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"om_disable_all_campaigns":false,"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[203],"tags":[],"class_list":["post-12365","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research-highlight","wpbf-post"],"aioseo_notices":[],"aioseo_head":"\n\t\t\n\t\n\t\n\t\n\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t