“Obese people suffer from osteoarthritis worse than non-obese people” sounds like non-news. After all, it’s common sense that carrying more weight on your joints will lead to more pain and wear-and-tear. However, the truth is more complex than that: non-weight-bearing joints (such as the hands) also see increased rates of osteoarthritis associated with obesity, suggesting that another factor is at work.
A team of researchers, including Krembil Senior Scientist Dr. Mohit Kapoor, Drs. Poulami Datta, Yue Zhang and Jason Rockel, identified this as an important gap in understanding: "We know that there is something circulating in the blood of those on a high-fat diet that causes the process to accelerate. This is what we decided to investigate."
The researchers used an experimental model to answer important questions about the relationship between obesity and osteoarthritis. This form of arthritis is the most common, with more than three million Canadians affected. Obese individuals have an increased incidence of the disease and are 33% more likely to require joint replacement surgery.
Dr. Kapoor’s team found that the consumption of a high fat diet (leading to obesity) could speed up the effects of osteoarthritis on cartilage degradation. They then identified a set of three molecules in the blood that could be used to predict the risk of developing osteoarthritis and the risk of increased severity. These molecules, called metabolites, are related to how fat is used by the body.
While eight metabolites are known to be associated with osteoarthritis, the new findings revealed that just three were needed to predict an increased risk of osteoarthritis severity. The research team also found that a hormone known to influence hunger, fat stores, metabolite levels and more—called leptin—was increased after the high fat diet. While blood levels of leptin returned to normal after switching back to a leaner diet, leptin levels in cartilage remained high for months. “The heightened levels of leptin in the joints that we observed may be key to understanding why the risk of osteoarthritis remains high for obese individuals, even after these individuals make positive lifestyle changes and lose weight,” says Dr. Kapoor.
The team is now taking these results to the clinic: they will be collecting and analysing blood samples obtained from actual patients at Toronto Western Hospital to investigate the interplay between obesity, the metabolites that they identified and leptin in osteoarthritis.
This work was supported by the Canadian Institutes of Health Research and the Toronto General & Western Hospital Foundation.
Datta P, Zhang Y, Parousis A, Sharma A, Rossomacha E, Endisha H, Wu B, Kacprzak I, Mahomed NN, Gandhi R, Rockel JS, Kapoor M. High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature. Sci Rep. 2017 Aug 15;7(1):8205. doi: 10.1038/s41598-017-07963-6.
The Peter Munk Cardiac Centre received the single-largest gift to a hospital in Canadian history, with the announcement of a "transformative"' commitment of $100 million from the Peter and Melanie Munk Charitable Foundation.
The announcement, made on September 19 at the Toronto General Hospital, drew a standing ovation from a crowd of patients, medical staff, researchers, business leaders and government officials.
The historic award will help advance a number of important initiatives at the PMCC, including a partnership with the Vector Institute, with funds to support the creation of a research team focused on using artificial intelligence to improve care. The gift will also support the development of the Digital Cardiovascular Health Platform, which will seamlessly integrate all clinical and research data—including new sources of data enabled by technology such as connected monitors, patient-reported information and next-generation sequencing. This platform will enable new research approaches, such as machine learning, to help clinical decision-making and to drive basic research.
"This gift will change the way that patients with heart and blood vessel disease are managed in Toronto, across Canada and around the world," says Dr. Barry Rubin, Medical Director, Peter Munk Cardiac Centre. "No other centre has what we have proposed—this will truly be world leading. With our colleagues at Techna, we will work together to commercialize the AI based approaches that we develop, to create new revenue streams that will support research at the intersection of AI and cardiovascular care.”
During the announcement, Mr. Munk gave a touching speech highlighting his love of Canada, and the obligation he feels to give back to the country that welcomed him and his family in 1948. “I’m not talking about charity, not talking about a gift—I’m talking about repaying a debt,” Mr. Munk stated, talking about the experiences of his family being accepted in Canada, and the care provided by the staff of Toronto General Hospital over the years.
This donation builds upon a legacy of two decades of support from the Peter and Melanie Munk Charitable Foundation, which now totals over 175 million dollars [CAD]. “Top people only come here if you give them the tools,” continued Mr. Munk, explaining how the donation will help PMCC, UHN and Toronto draw top clinical and research talent from around the world.
Link to UHN.ca story on the historic donation.
The Krembil Research Institute has partnered with The Globe and Mail to release a magazine series highlighting Krembil research advancements.
The third magazine in the series was distributed to Globe and Mail subscribers across Canada on September 7, 2017 and focuses on success stories in arthritis research. Read the full issue online here.
“At Krembil, we’ve diligently built one of the top research programs in the world dedicated to finding [the cure for arthritis],” says Dr. Nizar Mahomed, Medical Director of the Arthritis Program at UHN. “We employ a collaborative, innovative team-first approach that’s committed to stopping this disease in its tracks.”
The current issue features the following Krembil researchers and arthritis research projects:
Also featured are philanthropists Tony Fell and Bryce Douglas, who are the founding co-chairs of the Campaign to Cure Arthritis. As longtime supporters of the Arthritis Program at Toronto Western Hospital, they understand the devastating impact that arthritis can have on people’s lives and the economy, and why private sector donations are critical to finding cures.
“There are many exciting stories of progress and success emerging from our laboratories,” explains Dr. Donald Weaver. “Some of these stories are told in this magazine. This is only a sampling of what we do and what we are capable of.”
Links to all three Globe and Mail magazines are available here.
Dr. Gelareh Zadeh has been appointed as the Program Medical Director for the Krembil Neuroscience Centre at Toronto Western Hospital. She is an award-winning teacher, a highly published scientist and neurosurgeon with specialization and academic focus in neuro-oncology and skull base surgery.
Dr. Zadeh completed her neurosurgery training, and a PhD in brain tumor research at University of Toronto. She joined the neurosurgery division in 2008 as a surgeon-scientist. She is presently a Scientist at the PM Cancer Centre and Head of the Division of Surgical Oncology at UHN and Mount Sinai. She holds the Wilkins Family Chair in Brain Tumor Research, which aims to promote surgical clinical trials and translation of neuro-oncologic discoveries to clinical practice. She is also a scientist in the Macfeeters-Hamilton Neuro-oncology Program, a recognized program with strong peer review funding from national and international granting agencies.
Gelareh is internationally recognized in the field of neurosurgery and neuro-oncology and holds active roles in various societies as the Secretary/Treasurer of The Society of Neuro-Oncology (SNO) and North American Skull Base Society. Her research has been recognized through numerous awards: the America Brain Tumour Association Young Investigator Award, Society of Neuro-oncology Translational Award and the PAIRO Resident Advocate Award – given by the Residents and Interns Association of Ontario.
“The Krembil Neuroscience Centre is a program that serves many people throughout the Province of Ontario. Dr. Zadeh is a leader who is completely familiar with the program and its people and will work with everyone to ensure that Krembil continues to lead in all areas,” said Brian Porter, Chair of UHN’s Board of Trustees.
Please join us in congratulating Gelareh on her appointment. She is committed to promoting the Krembil Neuroscience Centre to advance clinical, academic and educational missions; working closely in partnership with the wide range of expertise and talent both within and outside of UHN.
Your genetic makeup is more than 99 percent similar to that of every other person. So, if we share so much similarity in our genes, what makes us different?
Part of the reason for our differences is that we inherit gene variants—called alleles—from our parents. While many alleles can exist for any given gene, each of us only has two per gene: one allele comes from our father and the other allele comes from our mother.
The different allele combinations for each of our tens of thousands of genes result in different observable traits, such as height or eye colour.
A new study by Krembil Senior Scientist Dr. Dafna Gladman shows that allele variation may also explain why some people are more susceptible to psoriasis, a common immune-mediated skin disease, and its related arthritis, psoriatic arthritis.
To demonstrate this, Dr. Gladman and her research team focused on the KIR3DL1 gene, which encodes a protein that is known to play a key role in activating the immune system. The team developed a genetic method to identify different KIR3DL1 alleles and classify them into four categories based on the corresponding state of the protein: high levels of protein, low levels of protein, null (undetectable) protein, and a shortened form of the protein.
Using this novel approach, the team identified and categorized KIR3DL1 alleles from 652 people with psoriatic disease (including 260 patients with psoriasis only and 392 patients with psoriatic arthritis) and 371 people without the disease. They found that the null protein category was more frequent in those without psoriatic disease. There was no difference between those with psoriasis alone and those with psoriatic arthritis.
"Our results suggest that when alleles fall within the ‘null’ category, they may confer some type of protection against psoriasis," explains Dr. Gladman. "Our work lays the foundation for the development of clinical tools that may help clinicians better predict who is at risk for developing the disease, enabling earlier treatments and preventing long-term consequences."
This work was supported by the Krembil Foundation, the Canadian Institutes of Health Research and the Toronto General & Western Hospital Foundation.
Berinstein J, Pollock R, Pellett F, Thavaneswaran A, Chandran V, Gladman DD. Association of variably expressed KIR3dl1 alleles with psoriatic disease. Clin Rheumatol. 2017 Aug 11. doi: 10.1007/s10067-017-3784-5.
Our bodies depend on electricity. Electrical signals are crucial for your heart to beat, and the electrical activity in your brain enables you to read and understand this sentence. When the electrical signaling goes awry, major health issues can arise.
Epilepsy is a neurological disorder characterized by recurrent surges of abnormal electrical activity in the brain that produce seizures. The cause of the surges is not well understood; however, researchers have shown that it can involve genetics, head trauma, developmental disorders, prenatal brain damage and infections.
Accurately diagnosing the cause of seizures is necessary for prescribing the best treatments. Despite this, in almost half of those affected by epilepsy, the cause of seizures is unknown.
Krembil Clinician Investigator Dr. Danielle Andrade recently examined the utility of a genetic test to help determine the cause of unexplained epilepsy in adults with intellectual disability (ID). The test detects a type of genetic alteration known as copy number variation (CNV), which has been linked to other diseases.
Dr. Andrade and her colleagues performed the genetic test on 143 adults and interpreted the results in the context of each patient’s clinical features. They found that a high proportion (16%) of these patients carried rare CNVs that contributed to their epilepsy. Of the CNVs identified, eight were found to affect genes previously implicated in ID, autism and/or epilepsy. Moreover, the researchers pinpointed five altered genes that most likely contributed to patients’ clinical features.
"This study shows that genetic testing could provide clinicians with important information that may improve the diagnosis and treatment of epilepsy. Adults with epilepsy of unknown cause should be re-investigated with the modern DNA technologies available today”, says Dr. Andrade.
This work was supported by the Ontario Brain Institute, the Government of Ontario and the Toronto General & Western Hospital Foundation. A Bassett holds a Tier 1 Canada Research Chair in Schizophrenia Genetics and Genomic Disorders.
Borlot F, Regan BM, Bassett AS, Stavropoulos DJ, Andrade DM. Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability. JAMA Neurol. 2017 August 28. doi:10.1001/jamaneurol.2017.1775
(TORONTO, Canada – Sept. 8, 2017) – A task force consisting of researchers from around the world and led by a scientist at the Krembil Research Institute in Toronto has released a set of recommendations that advise against the use of brain imaging as a test for chronic pain.
“It’s not possible at this point in time to say with any degree of certainty that a person does or does not have chronic pain based on brain imaging,” said Dr. Karen Davis, Head, Division of Brain, Imaging and Behaviour-Systems Neuroscience at UHN’s Krembil Research Institute and a Professor in the Department of Surgery and Institute of Medical Science at the University of Toronto. “The only way to truly know if someone is in pain is if they tell you because pain is subjective and it is a complex experience. No brain scan can do that.”
The recommendations of the task force—which consisted of clinicians, brain imaging researchers as well as experts in functional magnetic resonance imaging (fMRI), neuroethics and law—were published today in the journal Nature Review: Neurology in a paper titled “Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations”.
In recent years, advances in brain imaging have led to a shift in understanding of acute and chronic pain and prompted the search for brain-based biomarkers for key characteristics of pain. However, as brain imaging measures become more acceptable for directing personalized pain management, the demand is also growing for this data to be used for legal purposes, including the development of a potential ‘lie detector’ test for chronic pain.
“Use of such tools would be inappropriate and unethical,” said Dr. Davis. “This technology is not foolproof. There are vast issues of variability between people and even within a person at different times. As a result, brain imaging must not be used as a lie detector for chronic pain.”
The task force’s recommendations include the suggestion that any brain-based biomarkers should be used only as an adjunct to rather than a replacement for subjective reports of pain, even if testing is improved and valid protocols developed. Dr. Davis noted that the task force hopes the recommendation will be used as a blueprint by health care systems, governments and legal policy makers.
“We are working towards biomarkers for chronic pain, but the goal is not as a lie detector test but rather to help provide personalized pain treatment options for patients,” said Dr. Davis. “We expect many people will be relieved that there is now a blueprint in place for moving forward with this research. People outside of the field of imaging might be disappointed, but the fact of the matter is the technology cannot be used to support or dispute a claim of chronic pain.”
Story adapted from UHN.ca.
