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Diabetes is a medical condition characterized by high blood sugar levels that occurs when the body either doesn\u2019t produce enough insulin or doesn\u2019t have a proper response to insulin.<\/strong> Diabetes affects an estimated 9.4 percent of all Canadians and can result in potentially life-threatening complications.<\/p>\n One of these complications that often develops is diabetic kidney disease (DKD), which is the leading cause of kidney failure in North America.<\/p>\n [\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”2\/3″][vc_column_text]<\/p>\n \u201cDKD places a significant burden on our healthcare system,\u201d says Dr. Joan Krepinsky, a clinician-scientist at the Hamilton Centre for Kidney Research, which is part of The Research Institute of St. Joe\u2019s Hamilton. \u201cHowever, the current standard of care for DKD can only slow disease progression, with many patients developing end-stage kidney disease and requiring costly therapies including dialysis or kidney transplant. There is a major need to identify new therapeutic targets to prevent DKD progression.\u201d<\/p>\n Thankfully, Dr. Krepinsky and her team have uncovered a novel biological mechanism of DKD that has led them to a promising therapeutic target.<\/p>\n [\/vc_column_text][\/vc_column][vc_column width=”1\/3″][vc_single_image image=”185″ img_size=”150×150″ alignment=”center” css_animation=”none”][vc_column_text]<\/p>\n [\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_empty_space height=”16″][\/vc_column][\/vc_row][vc_row full_width=”stretch_row_content” full_height=”yes” parallax=”true” parallax_image=”1938″][vc_column][vc_empty_space height=”750″][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text css_animation=”slideInRight” css=”.vc_custom_1727282983779{background-color: #ffffff !important;}”]<\/p>\n Dr. Joan Krepinsky studies diabetic kidney disease (DKD) in her laboratory at St. Joe’s.<\/em><\/strong><\/p>\n [\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”2\/3″][vc_column_text]<\/p>\n Dr. Krepinsky is currently working with Novo Nordisk and the Empire Discovery Institute in a collaborative program called LeapRx to develop another type of treatment for DKD that may help prevent DKD from progressing. This treatment \u2013 known as peptide therapy \u2013uses a string of amino acids known as a peptide. Peptide therapy is very common in treating different conditions; for example, insulin and semaglutide (Ozempic\u00ae) treatments are just two types of peptide therapies that are commonly administered to manage diabetes.<\/p>\n [\/vc_column_text][\/vc_column][vc_column width=”1\/3″][vc_single_image image=”2064″ img_size=”medium” alignment=”center”][\/vc_column][\/vc_row][vc_row][vc_column] We tend to think about the pancreas when we hear diabetes, but other organs are involved in the condition as well. High blood sugar is the hallmark symptom of diabetes, and it can affect the cells inside the kidneys, potentially resulting in DKD.<\/p>\n High blood sugar specifically affects two proteins in the kidney: glucose-regulated protein 78 (GRP78) and alpha-2-macroglobulin (\u03b12M). In people with normal blood sugar levels, GRP78 works inside the kidney cells to help make sure the kidneys are functioning properly. When there is too much glucose in the bloodstream, such as in the case of diabetes, GRP78 can move from the inside of the cell to the cell surface. In this new location, it is known as cell surface GRP78, or csGRP78.<\/p>\n People with diabetes also have higher kidney levels of \u03b12M, which is usually a type of blood protein that can change its shape when it encounters certain enzymes. When this shape changes, a part of the \u03b12M molecule that was previously hidden becomes visible. This new configuration is known as activated \u03b12M, or \u03b12M*.<\/p>\n \u03b12M* typically isn\u2019t present in the kidneys, except in the case of high blood sugar. The newly revealed part of \u03b12M* fits very snugly with csGRP78. With csGRP78 residing on the surface of the kidney cells, these two proteins can come into frequent contact in the kidneys and bond together. Unfortunately, the bonding of these proteins causes a chain reaction that produces fibrotic tissue (scarring) in the kidneys. As scar tissue builds up, kidney function becomes worse over time and can eventually lead to kidney failure.<\/p>\n [\/vc_column_text][\/vc_column][\/vc_row][vc_row full_width=”stretch_row_content” full_height=”yes” parallax=”true” parallax_image=”1937″][vc_column][vc_empty_space height=”750″][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text css_animation=”slideInRight” css=”.vc_custom_1727283047181{background-color: #ffffff !important;}”]<\/p>\n Dr. Jackie Trink recently completed her graduate training in Dr. Krepinsky’s lab.<\/em><\/strong><\/p>\n [\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column] Dr. Krepinsky and her team are developing a peptide that can bond with \u03b12M* before GRP78 gets the chance to, meaning that csGRP78 and \u03b12M* won\u2019t be able to create any fibrotic tissue in the kidneys.<\/p>\n [\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”2\/3″][vc_column_text]\u201cStopping the interaction between these proteins may represent a new therapeutic target to prevent fibrosis development in DKD,\u201d said Dr. Jackie Trink, a former grad student of Dr. Krepinsky who worked closely on this project at St. Joe\u2019s. \u201cThe next step is to develop the peptide so that we can conduct human trials to determine how effective this treatment is.\u201d<\/p>\n Dr. Krepinsky is working with other researchers to take the next steps in developing this novel treatment. Dr. Anthony Rullo at McMaster University, who is an expert in how to make proteins and peptides, is currently helping to identify a version of it that is suitable for human trials. Dr. Matthew Lanktree, a clinician-scientist at the Hamilton Centre for Kidney Research, is conducting genetic analyses to investigate whether any genetic variants of csGRP78 or \u03b12M are associated with DKD. Finally, Yaseelan Palarasah, an investigator at the University of Southern Denmark, is providing critical reagents to be able to detect levels of the active form of \u03b12M in blood and urine. This will allow the team to more accurately determine how effective this peptide treatment is once they begin studying it in humans. It may also help to identify which people may benefit from treatment with the peptide.<\/p>\n [\/vc_column_text][\/vc_column][vc_column width=”1\/3″][vc_single_image image=”1987″ img_size=”medium” alignment=”center”][vc_single_image image=”1988″ img_size=”medium” alignment=”center”][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text]<\/p>\n This research project has the potential to prevent DKD from becoming worse and progressing to kidney failure, reducing the need for advanced therapies like dialysis and kidney transplant. With this novel peptide treatment, the healthcare system can see a reduced economic burden and, more importantly, many people living with diabetes may be able to enjoy a higher quality of life.<\/p>\n [\/vc_column_text][vc_separator][vc_empty_space height=”32″][vc_icon icon_fontawesome=”fas fa-book-reader” color=”custom” size=”xl” align=”center” custom_color=”#008b77″ link=”url:%2F2023%2Four-stories%2F|title:Our%20Stories”][vc_column_text]<\/p>\nKidney Research Pillar<\/h6>\n
How Diabetes Affects the Kidneys<\/span><\/span><\/span><\/h3>[vc_empty_space][vc_column_text]<\/p>\n
Benefits of Peptide Treatment<\/span><\/span><\/span><\/h3>[vc_empty_space][vc_column_text]<\/p>\n