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    Science Saturday: 10 significant Mayo Clinic Center for Individualized Medicine studies of 2021

It has been an impactful year of genomic and multi-omic research and scientific discoveries in Mayo Clinic's Center for Individualized Medicine. While much focus in 2021 was centered on advancing the knowledge of COVID-19, Mayo scientists and physicians have also worked to develop individualized treatments, prevention measures and diagnostics for patients with rare and undiagnosed diseases, cancer and other illnesses. 

As a new year approaches, here's a look back at 10 of Mayo Clinic’s influential precision medicine research studies in 2021. Highlights include treating neurological diseases with gene therapy, predicting individualized treatments for depression and rheumatoid arthritis using artificial intelligence, diagnosing rare diseases by identifying genomic variants, and saving lives with exome sequencing.  

  1. Mayo Clinic algorithm shows potential in individualizing treatment for depression 

Researchers have developed an artificial intelligence algorithm to help clinicians accurately and efficiently predict whether a patient with depression will respond to an antidepressant. The new research, published in Neuropsychopharmacology, represents a possible step forward in individualizing treatment for major depressive disorder.  

"We used the algorithm to identify the specific depressive symptoms and thresholds of improvement that were predictive of antidepressant response by four weeks for a patient to achieve remission or response, or a nonresponse, by eight weeks." - Arjun Athreya, Ph.D., a computer scientist within Mayo Clinic’s Molecular Pharmacology and Experimental Therapeutics. 

"The model generates output in a way that clinicians are able to easily assimilate, interpret and potentially use in the limited time they have in clinical visits with the patients." - William Bobo, M.D., chair of Mayo Clinic Florida's Psychiatry and Psychology. Read more.

  1. Newly discovered genetic variants in a single gene cause neurodevelopmental disorder, Mayo study finds 

Genetic variants in a neuro-associated gene called SPTBN1 are likely responsible for causing a neurodevelopmental disorder, according to a new Mayo Clinic study. For the global study, researchers investigated disease-causing variants of the SPTBN1 gene in 29 people with clinical neurodevelopmental symptoms, including language and motor delays, intellectual disability, autistic features, seizures, behavioral and movement abnormalities, and variable dysmorphic facial features.  The discovery, published in Nature Genetics, is a first step in finding a potential therapeutic strategy for this disorder, and it increases the number of genes known to be associated with conditions that affect how the brain functions.  

"The gene can now be included in genetic testing for people suspected of having a neurodevelopmental disorder, which may end the diagnostic odyssey these people and their families have endured." - Margot Cousin, Ph.D., a translational genomics researcher. Read more.

  1. Data show clear benefit from genetic testing before prescribing antiplatelet therapy 

Mayo Clinic researchers revealed a clear advantage of genetic testing in helping health care providers choose the appropriate anti-platelet drug for patients to prevent complications from blood clotting after a procedure to open clogged arteries. The meta-analysis published in JACC: Cardiovascular Interventions, shows testing helps determine if a patient carries genetic variants in CYP2C19 that cause loss of its function. These variants interfere with the body's ability to metabolize and activate clopidogrel, an anti-platelet medication. 

"With the help of genetic testing, we could safely prescribe generic, well-tolerated, once-daily clopidogrel to most patients and reserve the use of the newer, more expensive drugs ― ticagrelor or prasugrel ― for those with the loss-of-function genetic variants." -  Naveen Pereira, M.D., a Mayo Clinic cardiologist. Read more.

  1. Mayo Clinic research finds immune system responds to mRNA treatment for cancer 

Adding messenger RNA, or mRNA therapy improves the response to cancer immunotherapy in patients who weren't responding to the treatment, Mayo Clinic research shows. Immunotherapy uses the body’s immune system to prevent, control and eliminate cancer. The study is published in Cancer Immunology Research, a journal of the American Association for Cancer Research.

"We found that by introducing mRNA in immune cells, it is possible to produce useful proteins to improve their anti-tumor activity without attempting to change the genome itself. This approach may have the potential to be used across the spectrum of medicine to pull information gained from single-cell RNA-sequencing into mRNA-based therapy for patients." - Haidong Dong, M.D., Ph.D., a Mayo Clinic cancer researcher. Read more.

  1. Mayo study finds colon cancer driven by hereditary gene mutations in 1 in 6 patients 

In a recent Mayo Clinic study, nearly 1 in 6 patients with colorectal cancer had an inherited cancer-related gene mutation that likely predisposed them to the disease. In addition, the researchers discovered that 60% of these cases would not have been detected if relying on a standard guideline-based approach. The study is published in Clinical Gastroenterology and Hepatology

"The power of genetics is that we can foresee the cancer that will develop in other family members. This can allow us to target cancer screening to those high-risk individuals and hopefully prevent cancer altogether in the next generation of the family." -  Niloy Jewel Samadder, M.D., a Mayo Clinic gastroenterologist and hepatologist. Read more.

  1. Mayo researchers develop algorithm to predict rheumatoid arthritis disease activity 

A first-of-its-kind machine learning algorithm developed by Mayo Clinic researchers can predict rheumatoid arthritis disease activity in a patient. The algorithm analyzes biochemical metabolites ― the product of the body's metabolism ― in blood. The study,  published in Arthritis Research & Therapy, lays the groundwork for monitoring rheumatoid arthritis disease progression and systemic inflammation using blood samples alone.  

"Having fast, reliable and scalable measures for predicting the clinical course of disease activity is an important unmet need for patients with rheumatoid arthritis. We turned to the blood because it could potentially provide a treasure-trove of novel biomarkers for assessing not only disease activity, but also clinical subgroups, risk factors and predictors of treatment response that complement current standard laboratory tests." -  Jaeyun Sung, Ph.D., a computational biologist. Read more.

  1. First hybrid gene therapy shows early promise in treating long QT syndrome  

Mayo Clinic researchers provided the first preclinical, proof-of-concept study for the use of hybrid gene therapy in long QT syndrome, a potentially lethal heart rhythm condition. In the study, published in Circulation, researchers demonstrated its potential therapeutic efficacy in two in vitro model systems using beating heart cells reengineered from the blood samples of patients with type 1 long QT syndrome. 

"Gene therapy is an emerging area of interest for treating a variety of genetic heart diseases in general and long QT syndrome in particular." Michael Ackerman, M.D. Ph.D. a Mayo Clinic genetic cardiologist and director of Mayo Clinic's Windland Smith Rice Comprehensive Sudden Cardiac Death Program. Read more.

  1. Mayo researchers reveal gene therapy path for treating children with rare, fatal genetic disease 

Mayo Clinic researchers have developed a gene therapy technique to replace the defective genes that cause propionic acidemia, a rare and fatal genetic disease that often sickens babies in their first days of life. The key to the approach is an adeno-associated virus, which is known for infecting people without causing disease. These viruses are experts at penetrating cell walls and shuttling a repair gene to the cell's nucleus, where it is expressed to provide the missing functions. 

"Our approach is to give these patients a good copy of the gene to counteract the disease as best we can. This restores the ability of cells in the body to process these food components and reduce the production of toxic chemicals." -  Michael Barry, Ph.D., a gene therapy expert.  Read more.

  1. Large-scale exome sequencing project spots disease-fueling mutations to save lives, accelerate discoveries  

 Mayo Clinic is sequencing the exomes of tens of thousands of people from diverse backgrounds to investigate large-scale patterns of distinctive mutations that fuel disease. Exome sequencing analyzes almost all the 20,000 genes that provide instructions for making proteins, which play many critical roles in the body. This is where most known disease-causing mutations occur. As researchers are investigating volumes of data in pursuit of translational discoveries, research participants are learning if they carry disease-causing mutations . Detecting inherited genetic diseases early, or even before symptoms have a chance to develop, could save the lives of patients and their family members. 

"As we know, we are made of genes, proteins, metabolites, exposures. This is what defines us as humans in health and disease. So, imagine if we can not only understand the gene part, but also our metabolites, our exposures of a lifetime, our proteins ― and how those together interact in a human to create disease or wellness. The potential of this project is immense." Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for Mayo Clinic's Center for Individualized Medicine. Read more.

  1. Uterine microbe found to have disease-causing behavior in endometrial cancer 

A tiny microbe thriving in the uterine microbiome — a population of bacteria, viruses, yeasts/fungi in and around the uterus— could be a contributing driver of endometrial cancer, according to a new Mayo Clinic study. The discovery advances the understanding of this microbe and paves a path to identifying new therapeutic targets. 

"We have found that a microbe that is particularly associated with endometrial cancer is capable of pathogenic behavior and is stimulated by one of the main risk factors for the disease — estrogen exposure. Our discovery advances our understanding of this microbe and moves us closer to identifying new therapeutic targets." - Marina Walther-Antonio, Ph.D., whose research focuses on the human microbiome's role in women's health, in particular gynecologic cancers.  Read more.

What's ahead for 2022? 

Mayo Clinic plans to further integrate genomic medicine into clinical practice — particularly in rare disease and cancer — and push the bounds of "omics" discoveries, powered by sophisticated research and artificial intelligence.  

"We're in a unique position to fuel new discoveries to improve care for our patients, particularly in the space of rare diseases, which affect nearly 30 million Americans. At the same time, we'll continue to illuminate biochemical markers that could help us predict disease development through understanding multi-omics," says Konstantinos Lazaridis, M.D.the Carlson and Nelson Endowed Executive Director for Mayo Clinic's Center for Individualized Medicine. 

Dr. Lazaridis also plans to lead his team in putting a razor-sharp focus on the exposome — the measure of all the exposures of a person in their lifetime and how those exposures relate to health. 

"We believe that a profound understanding of environmental contributors to disease and health, when combined with genomics, could lead to vast improvements in knowledge of the causes and risk factors for many diseases." 

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