Study identifies potential new drug for Parkinson's-related cognitive decline, dementia

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id="block-az-barrio-content" class="block block-system block-system-main-block"> <div class="content"> <article class="node node--type-az-news node--view-mode-full clearfix"> <header> </header> <div class="node__content clearfix"> <div id="news-layout-row" class="row"> <div id="news-left-column" class="col-xl-8"> <div id="news-full-row-article-top" class="row"> <div class="col-12"> <div id="news-full-title-block" class="border-bottom align-text-top mb-4"> <h1 class="text-midnight"><span class="field field--name-title field--type-string field--label-hidden">Study identifies potential new drug for Parkinson's-related cognitive decline, dementia</span> </h1> <div class="standard-byline-published-block"> By Anna Christensen, College of Medicine – Tucson <div class="text-muted"> <div class="field field--name-field-az-published field--type-datetime field--label-hidden field__item">Nov. 21, 2024</div> </div> </div> <div class="sharethis-inline-share-buttons my-3"> </div><div class="views-element-container"><div class="uannounce-memo-info mb-3 view view-eva view-uannounce-eva-header view-id-uannounce_eva_header view-display-id-entity_view_1 js-view-dom-id-395e1e0e5081daa17627f9713b3d21e2f9d23dfbded8057dc1ce9a4f4c82063e"> </div> </div> </div> <figure > <div class="field field--name-field-az-media-image field--type-entity-reference field--label-hidden field__item"><div> <figure style="max-width: 1140px;"> <div class="field field--name-field-media-az-image field--type-image field--label-visually_hidden"> <div class="field__label visually-hidden">Image</div> <div class="field__item"> <img loading="lazy" class="img-fluid image-style-az-large" src="https://cdn.uanews.arizona.edu/s3fs-public/styles/az_large/public/2024-11/Kelsey-Bernard_0.JPG.webp?VersionId=zAlXrd_GURs6mraNIgq3m6f9WZx0ocYs&itok=nODlymEI" width="1140" height="763" alt="This image shows a woman smiling while working in a laboratory setting, looking into the eyepiece of a microscope. A computer screen in the background displays a vibrant, microscopic image, likely of a biological sample, alongside laboratory equipment and notes on the desk." /> </div> </div> <figcaption class="figure-caption"> <div class="clearfix text-formatted field field--name-field-az-caption field--type-text-long field--label-hidden field__item"><p>Kelsey Bernard was the first author on a paper that showed the protein PNA5 could possibly prevent cognitive decline in people who have Parkinson’s disease and related disorders.</p> </div> <cite class="small"> <div class="clearfix text-formatted field field--name-field-az-credit field--type-text field--label-hidden field__item"><p>Kris Hanning/U of A Health Sciences</p> </div> </cite> </figcaption> </figure> </div> </div> </figure> </div> </div> <div > <div > <div class="field field--name-field-az-body field--type-text-long field--label-hidden field__item"><p>A study by researchers at the <a href="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e628871db570ab9ef760856d4c6072a51f28bfe28d4d045a594bf26008b356357fcd632022adfb7894e4f7584eb4b108ee3" title="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e628871db570ab9ef760856d4c6072a51f28bfe28d4d045a594bf26008b356357fcd632022adfb7894e4f7584eb4b108ee3">University of Arizona Health Sciences</a> found that a tiny protein called PNA5 appears to have a protective effect on brain cells, which could lead to treatments for the cognitive symptoms of Parkinson's disease and related disorders. </p> <p>Parkinson's disease, a neurological disorder best known for causing tremors, stiffness, slow movement and poor balance, also causes cognitive symptoms that can progress to Parkinson's dementia. While there are medications that control the disease's motor symptoms, there are no effective treatments for its cognitive symptoms. </p> <p>"When patients are diagnosed with Parkinson's disease, 25% to 30% already have mild cognitive impairment. As the disorder progresses into its later stages, 50% to 70% of patients complain of cognitive problems," said Dr. Lalitha Madhavan,<strong> </strong>an associate professor of neurology at the <a href="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e62a5674797e5a56bff34815b28a3ae3c5be459a57f2ef2059a1cde79072bed14c3e6e59975ded7afda8fe23fa5e49cd0e8" title="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e62a5674797e5a56bff34815b28a3ae3c5be459a57f2ef2059a1cde79072bed14c3e6e59975ded7afda8fe23fa5e49cd0e8">University of Arizona College of Medicine – Tucson</a>. "The sad part is we don’t have a clear way to treat cognitive decline or dementia in Parkinson’s disease."</p> <p>A research team led by Madhavan, in collaboration with Torsten Falk, a research professor of neurology, is investigating PNA5, which was developed by Meredith Hay, a professor of physiology. They recently published a paper in <a href="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e6212fe9f9df0bcb6827cda69c933dffc7dac9a44645bfe5edbd091b185fdddfccdd72527cf6572fc507f195b409a1c738a" title="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e6212fe9f9df0bcb6827cda69c933dffc7dac9a44645bfe5edbd091b185fdddfccdd72527cf6572fc507f195b409a1c738a">Experimental Neurology</a> showing that, in an animal model, PNA5 appears to have a protective effect on brain cells. </p> <p>"With PNA5, we're targeting cognitive symptoms but, in particular, we're trying to prevent further degeneration from occurring," said Kelsey Bernard, a postdoctoral researcher in the <a href="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e62fdd23b19356ea375b6b18dd26e8d5470e9b37aa5063dc73a0e866d67fa8618fe3188b63fc6562cd90329e053b50483fa" title="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e62fdd23b19356ea375b6b18dd26e8d5470e9b37aa5063dc73a0e866d67fa8618fe3188b63fc6562cd90329e053b50483fa">Madhavan Lab</a> and the study's first author. "By going down the protective route, we can hopefully prevent cognitive decline from continuing."  </p> <h4><strong>Dialing back inflammation</strong></h4> <p>The causes of neurodegenerative diseases are largely mysterious, but the current thinking is that they involve inflammation, a normal function of the immune system that is usually short-lived in response to infections or wounds. If inflammation becomes chronic, however, it can do lasting damage. </p> <p>Bernard said inflammation plays a significant role in Parkinson's disease when microglia, specific immune cells in the brain, enter a supercharged state. </p> <p>"Normally, microglia are looking for things like viruses or injury and secreting substances that block off the damage," she said. "In Parkinson's disease, when they're constantly activated, microglia can propagate further damage to the surrounding tissue. That's what we see in Parkinson's brains, particularly in regions associated with cognitive decline."</p> <p>The team found that these supercharged microglia flooded their environments with an inflammatory chemical, supporting previous research linking that chemical with cognitive status. </p> <p>"This inflammatory chemical can directly interact with neurons in a region of the brain important for learning and memory," Bernard said. </p> <p>After treatment with PNA5, researchers watched blood levels of the inflammatory chemical decrease, correlating with a reduced loss in brain cells. They said they believe PNA5 dials back the microglia's overly active immune response and brings it closer to a normal state. </p> <p>The researchers hope that by suppressing production of this inflammatory chemical, PNA5 can protect the brain. </p> <h4><strong>Expanding treatment options </strong></h4> <p>When developing PNA5, Hay, in collaboration with Robin Polt, a professor of chemistry and biochemistry at the U of A College of Science, made small tweaks to the structure of a chemical the body naturally makes, enhancing its ability to enter the brain and stay there longer. Hay is studying PNA5's potential in treating other types of dementia, such as <a href="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e62695b43e8a3b6e0056358cffb75446f62506bc0923313ba49ac42087165ed2fe6862b33ead6406035fce7fe672002c2e9" title="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e62695b43e8a3b6e0056358cffb75446f62506bc0923313ba49ac42087165ed2fe6862b33ead6406035fce7fe672002c2e9">vascular dementia</a> and Alzheimer's disease. </p> <p>"It has already been tried and tested in other models, and that makes me more optimistic," said Madhavan, who, along with Polt and Hay, is a member of the <a href="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e62666496d30cc26329087d83540e6232e1331f9454007533238e9a73f83aafdaae99780a61b5a16ca9bbef0dc15aedd6c8" title="https://click.comms.arizona.edu/?qs=13a6dcf3e5584e62666496d30cc26329087d83540e6232e1331f9454007533238e9a73f83aafdaae99780a61b5a16ca9bbef0dc15aedd6c8">BIO5 Institute</a>. </p> <p>She said she hopes the team's investigations into PNA5 will eventually lead to a drug that people with Parkinson's disease can take to alleviate cognitive symptoms, though they may still need to take other drugs to control motor symptoms. </p> <p>"I think about it as a cog in the wheel — there are going to be other drugs that support other aspects of Parkinson's. Taking multiple drugs is never fun, but it's a complex condition and there can only be complex solutions," she said. "The beauty of the brain is the interconnectedness, but it also adds to the complexity." </p> <p>The researchers said their next steps are to conduct further studies to identify biomarkers, refine dosages, investigate sex differences and figure out how PNA5 might work. </p> <p>"PNA5 seems to have a possibility of stopping or delaying Parkinson's progression to some extent and could improve the health of brain cells or prevent cells from dying," Madhavan said. </p> <p>The publication was the product of Bernard's doctoral research, which she performed under the mentorship of co-senior authors Madhavan and Falk. </p> <p>"The brain is the most interesting part of the body," Bernard said. "These cells are fascinating — what causes them to work correctly and what causes them to go awry."</p> <p><em>This research was supported in part by the Michael J. Fox Foundation under award No. MJFF 024922, the National Institutes of Health under award No. T32 AG1081797, and the ARCS Foundation Scholarship. </em></p> </div> </div> </div> </div> <div id="news-layout-right-column" class="col-xl-4"> <div > <h3>Topics</h3> <div class="field field--name-field-custom-news-categories field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news-story-categories/health-wellness" hreflang="en">Health & Wellness</a></div> </div> </div> <div > <h3>Tags</h3> <div class="field field--name-field-az-news-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news-tags/college-medicine-tucson" hreflang="en">College of Medicine - Tucson</a></div> <div class="field__item"><a href="/news-tags/research" hreflang="en">Research</a></div> <div class="field__item"><a href="/news-tags/bio5" hreflang="en">BIO5</a></div> <div class="field__item"><a href="/news-tags/medicine" 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