Monthly Archives: April 2022

Posted on 02/22/2022

Eli Lilly and Company (NYSE: LLY) revealed the creation of the Lilly Institute for Genetic Medicine and an investment of approximately US$ 700 million to establish a state-of-the-art facility at a new site in the Boston Seaport. This investment part of the companys strategy to advance RNA based therapeutics builds on the 2020 acquisition and rapid expansion of Prevail Therapeutics, a gene therapy company based in New York City.

Through the work of the Institute, Lilly intends to fuel the development of genetic medicines, which already account for more than 20% of Lillys diabetes, immunology, and central nervous system research portfolio. Within 5 years, Lilly projects the Boston site will grow from 120 to more than 250 research biologists, chemists, data scientists and other experts in genetic medicine, while the New York site will grow to include up to 200 scientists all employed by Lilly.edicines that make life better for people around the world.

The Institute will be headquartered in 334,000 sq. ft. of leased space in a 12-story building, developed and operated by Alexandria Real Estate Equities, Inc., in the rapidly expanding Seaport district of Boston. Occupancy of the new site is scheduled for 2024.

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Eli Lilly and Company Launches the Lilly Institute for ...

Its recognized that daily prednisone promotes obesity, but a new preclinical study by Northwestern Medicine researchers has shown that once-weekly prednisone has very different results, promoting nutrient uptake into muscles and improving lean body mass. The teams research showed that obese mice fed a high-fat diet (HFD) and receivingthe glucocorticoid steroid prednisone just once per week had improved exercise endurance, became stronger, lost weight, and demonstrated increased lean body mass. The treated animals also exhibited increased muscle metabolism, and increased levels of adiponectin, a fat-derived hormone that appears to play an important role inprotecting against diabetes and insulin resistance.

Daily prednisone is known to promote obesity and even metabolic syndromea disorder with elevated blood lipids and blood sugar and weight gain, said Elizabeth McNally, MD, PhD, director of the Center for Genetic Medicine at Northwestern University Feinberg School of Medicine. So, these results, in which we intermittently pulse the animals with once-weekly prednisone, are strikingly different. Obesity is a major problem, and the idea that once-weekly prednisone could promote nutrient uptake into muscle might be an approach to treating obesity.

McNally and colleagues reported on their findings in the Journal of Experimental Medicine, in a paper titled, Intermittent prednisone treatment in mice promotes exercise tolerance in obesity through adiponectin. In their paper the researchers concluded, Our study demonstrates that intermittent glucocorticoids produce healthful metabolic remodeling in diet-induced obesity. McNally is a Northwestern Medicine physician and the Elizabeth J. Ward professor of genetic medicine.

Fatmuscle communication regulates metabolism and involves circulating signals like adiponectin, the author explained. Modulation of this cross-talk could benefit muscle bioenergetics and exercise tolerance in conditions like obesity. Many patients take prednisone daily for different immune conditions. Known side effects of daily prednisone include weight gain and even muscle atrophy with weakness. The authors noted, Glucocorticoid steroids such as prednisone are widely used immune suppressants and their chronic daily intake promotes metabolic stress and obesity.

The team had been interested in finding out whether patients can get the same immune benefit with intermittent prednisone dosing, which could be much more beneficial to the muscle. In previously published research, McNallys team discovered that giving prednisone intermittently was helpful for muscular dystrophy, and they demonstrated that once-weekly prednisone improved strength.The group also recently reported findingsfrom a pilot clinical trial in individuals with muscular dystrophy, in which one weekly dose of prednisone improved lean mass.

The newly reported research in mice with dietary obesity showed that intermittent once-weekly prednisone increased adiponectin levels and improved exercise tolerance and energy expenditure. The effects were dependent on adiponectin, as adiponectin gene knockout (Adipoq-KO) mice failed to benefit from weekly prednisone therapy. Intermittent prednisone promoted muscle metabolism and exercise tolerance through adiponectin, the team commented, and added, treatment failed to improve adiposity, exercise tolerance, and insulin tolerance with HFD in Adipoq-KO mice.

The scientists also showed that the benefits of once-weekly prednisone therapy also extended to mice that were already obese from eating a high-fat diet, with treated animals experiencing increased strength, running capacity, and lower blood glucose. Opposite to daily dosing, intermittent prednisone blunted weight accrual and improved strength, treadmill endurance, and glucose homeostasis in mice with pre-established obesity, the investigators stated. The studies confirmed that the favorable metabolic effects of prednisone were specific to the intermittent dosing even in mice already obese before treatment.

Most of what has previously been known about steroids such as prednisone has resulted from studies investigating the effects of taking prednisone every day. We see a very different outcome when it is taken once a week, said McNally. We need to fine-tune dosing to figure out the right amount to make this work in humans, but knowing adiponectin might be one marker could provide a hint at determining what the right human dose is.

McNally described the weekly dose as a bolus, or spike, of nutrients going into your muscle. She said, We think there is something special about promoting this spike of nutrients into muscle intermittently, and that it may be an efficient way to improve lean body mass.

Corresponding author, Mattia Quattrocelli, PhD, added, What is exciting to me about this work is the finding that a simple change in the dosing frequency can transform glucocorticoid drugs from inducers to preventers of obesity. Chronic once-daily intake of these drugs is known to promote obesity. Here we show that dosing the same type of drug intermittentlyin this case, once weeklyreverses this effect, promotes muscle metabolism and energy expenditure, and curtails the metabolic stress induced by a fat-rich diet. Quattrocelli, who initiated the research while at Northwestern, is now assistant professor at Cincinnati Childrens Hospital Medical Center and department of pediatrics at the University of Cincinnati.

People have different responses to prednisone dosing so McNally wants to determine which biomarkers are most critical to mark having a beneficial response to prednisone. If we can determine how to choose the right dose of prednisone that minimizes atrophy factors and maximizes positive markers like adiponectin, then we can really personalize the dosing of prednisone, she said.

The group also recently showed that weekly prednisone uses strikingly different molecular pathways to strengthening the muscle in male versus female mice, based on a recently published studyby Isabella Salamone, a graduate student in McNallys lab.

The benefits of weekly prednisone are linked to circadian rhythms, reported another recent study from Northwestern and University of Cincinnati. Human cortisol and steroid levels spike early in the morning before you wake up.If you dont give the drug at the right time of day, you dont get the response,Quattrocellisaid. In mice, we obtained good effects with intermittent prednisone in muscle mass and function when we dose them at the beginning of their daytime. Mice have a circadian rhythm inverted to us, as they generally sleep during the daytime and are active at night. This could mean that the optimal dosing time for humans during the day could be in the late afternoon/early evening, but this needs to be appropriately tested.

McNally remains cautious about making inferences on the potential clinical applications of intermittent prednisone. These studies were done in mice, she acknowledged. However, if these same pathways hold true in humans, then once-weekly prednisone could benefit obesity.

She further noted, While we are encouraged by the pilot study in humans with muscular dystrophy, mouse muscles have more fast-twitch fibers than humans, and slow-twitch muscle could be different. More studies are needed to try to better understand whether these same mechanisms work in human muscles.Nevertheless, the authors stated in their newly released paper, In conclusion, our study reported that intermittent prednisone promoted a virtuous fat-muscle communication through adiponectin. These findings pave the way for adjuvant drug strategies to restore adiponectin sensitivity and exercise tolerance in conditions of metabolic stress.

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Could Weekly, Not Daily Prednisone Represent A New Approach to Obesity Therapy? - Genetic Engineering & Biotechnology News

This genetic risk score may help health care providers identify the risk of heart disease earlier and take preventive measures.

Vibhu Parcha, M.D., first author of this study and a clinical research fellow in the Division of Cardiovascular Diseases and the UAB Cardiogenomics Clinic. (Photography: Lexi Coon)According to the Centers for Disease Control and Prevention, more than 37 million Americans have diabetes, and approximately 90-95 percent of them have Type 2 diabetes. Individuals with Type 2 diabetes are at an increased risk of poor cardiovascular outcomes, leading to an estimated $37.3 billion a year in heart disease-associated care.

A new study involving two researchers from the University of Alabama at Birmingham Division of Cardiovascular Disease states that a genetic score can predict the likelihood of high blood pressure and its connection to poor cardiovascular outcomes in people with Type 2 diabetes.

The study, published today in the American Heart Associations peer-reviewed journal titled Hypertension, could play a pivotal role in guiding treatment for people who are newly diagnosed with Type 2 diabetes or those with prediabetes. In this study, researchers explored whether genetic variants linked with high blood pressure are connected to the risk of heart disease or stroke for people with Type 2 diabetes.

Identifying the genetic risk of high blood pressure among newly diagnosed patients with diabetes may help with more targeted efforts to prevent the development of heart-related events in the future, said Pankaj Arora, M.D., associate professor in the UAB Marnix E. Heersink School of Medicines Division of Cardiovascular Disease and the director of the UAB Cardiogenomics Clinic. In the current era of precision medicine, we want to find the individualized approach of understanding the risk of heart disease in a person newly diagnosed with diabetes. This allows focusing our clinical efforts in preventing the occurrence of fatal heart events through a personalized approach based on their genetic risk.

Researchers analyzed the health records of 6,335 participants from the Action to Control Cardiovascular Risk in Diabetes trial database. Thirty percent of participants were racial minorities, and 37 percent of participants were women. Each candidate had Type 2 diabetes and elevated blood pressure.

They reviewed multiple health factors including blood pressure, cholesterol and blood sugar levels all commonly used to determine a persons risk for heart disease and reviewed their age, sex, body mass index, medical history and genetic history, among other factors. Through their analysis, researchers established a genetic risk score, which estimates a persons chance of developing heart disease within the next 10 years.

To develop this risk score, researchers used a genetic variant map of more than 1,000 common genetic variants known to affect blood pressure and compared it to the DNA of study participants to determine their genetic risk. More matches between a participants DNA and these genetic variants would mean a higher genetic risk score.

Pankaj Arora, M.D., associate professor in the UAB Division of Cardiovascular Disease and the director of the UAB Cardiogenomics Clinic.(Photography: Andrea Mabry)Commonly occurring changes in our DNA form the composite genetic risk score for an individual, said Vibhu Parcha, M.D., first author of this study and a clinical research fellow in the Division of Cardiovascular Diseases and the UAB Cardiogenomics Clinic. Since we are born with these commonly occurring DNA changes, we carry the risk for heart conditions conferred by them throughout our lifetime. We were curious to understand whether a high genetic risk score for blood pressure would help us identify individuals with diabetes who are at a higher risk of fatal heart events.

Researchers found that the genetic risk score identified study participants with a higher risk of cardiovascular events. This genetic score may help identify the risks for diseases earlier and allow doctors to take preventive measures among people with Type 2 diabetes.

This study represents a step toward personalized medicine for heart disease that stems from Type 2 diabetes and high blood pressure, said David Goff, M.D., Ph.D., director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

Other authors involved in the study are Akhil Pampana, M.S.; Adam Bress, Pharm.D., M.S.; Marguerite R. Irvin, Ph.D.; and Garima Arora, M.D.

We look forward to future studies to confirm and build on these findings, said Goff, who is not a member of the current study team. Studies such as this with diverse populations could also help inform efforts to reduce health disparities associated with heart disease. Future studies might also test whether interventions guided by this type of knowledge are more effective than current strategies.

The UAB Cardiogenomics Clinic uses a patients genetic history to help develop a personalized cardiovascular treatment plan based on their genetic results. The clinic provides a broad spectrum of cardiology health care services for people of all ages and those with all types of heart diseases in the southeastern United States. Make an appointment today by visiting uabmedicine.org or calling 205-975-2313.

Research reported in this release was supported in part by the National Heart, Lung, and Blood Institute, part the National Institutes of Health, under grant numbers R01HL160982 and K23HL146887. The study includes data from the multiethnic ACCORD trial, which was sponsored by the NHLBI. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Researchers find that genetic scores may identify risk of heart disease for people with Type 2 diabetes - University of Alabama at Birmingham

The goal of reaching an era of individualized precision medicine will first require a closer look at the broader population.

The big picture: Large clinical trials and massive databases of de-identified genetic and other health information sometimes from generations of populations are offering scientists and doctors data to decipher why certain individuals have a higher risk of disease or different responses to treatments.

What's happening: There are many institutions gathering this data, including...

What's new: The COVID-19 pandemic led various groups to collectively create large-scale studies to seek safe and effective COVID treatments as rapidly as possible, such as the U.K.'s Recovery trial on more than 47,000 participants and the WHO's Solidarity Therapeutics Trial on 14,200 randomized hospitalized patients globally.

Growing awareness of the problems caused by a lack of diversity in clinical trials and in most genetic databases has led to other changes.

Reality check: Personalized medicine continues to face serious challenges, and has sometimes resulted in deadly missed targets. But many hope accumulating data from large, more diverse trials will help alleviate those issues.

Between the lines: Large cohort studies are one of the key "strategies to be able to understand the risk factors associated with cancer and with other diseases," says Marcia Cruz-Correa, physician-scientist at the University of Puerto Rico Comprehensive Cancer Center.

The bottom line: These massive datasets are expected to help tease out the biological and socioeconomic factors of disease, Oh says. "They're all tied together."

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The power of massive databases and trials to unlock precision medicine - Axios

Cancer is a difficult disease to treat. Figuring out exactly what chemotherapy or immunotherapy treatment will perform best for a specific cancer patient can be a difficult task for physicians. There is no sure fire way of knowing exactly how a patient will react to a certain type of anticancer drug. And, unfortunately, time usually isnt abundant to perform trial-and-error, especially in particularly aggressive types of cancer.

Genetic profiling has been the traditional approach in aiding physician decisions with limited success. Even if certain mutations in the cancer are identified, it still boils down to an educated guess based on previous patients. Its not quite the personalized medicine that physicians and scientists have been searching for.

However, scientists from Ohio State University have come up with a solution that could prove to truly be a personalized approach to knowing exactly how a patient will react to different cancer drugs. These scientists took cancer tissue from melanoma patients and created petri-dish versions of their bodies to test which drug would be most effective. Melanoma is a type of cancer that originates from mutations to pigment in our skin called melanin. It is an incredibly aggressive type of cancer that can quickly spread to other parts of the body.

But creating these test tube patients to experiment on was not an easy task. Our bodies are made up of intricate biochemical systems, most of which we still dont completely understand in terms of cancer progression. In order to create the best possible replication of cancer in our bodies, these scientists came up with a way to combine cancer tissue from patients and important immune cells found in their lymph nodes using a thick substance called extracellular matrix (ECM) hydrogel.

Every cell has an extracellular matrix that serves as a barrier between the cells and their environment. The hydrogel that these scientists used served to mimic this important barrier. The hydrogel was able to keep the cancer and lymph node tissue together, while still allowing for dynamic movement of the cancer drugs across the membrane to mimic what happens in our bodies own cells.

Once these synthetic organoids were made using tissues from each patient, they tested to see how long these organoids would maintain their ability to simulate the inside of the patient. After 7 days of the tissues sitting at around body temperature (99F) without any treatment, the scientist used a type of dye to see how alive these new tissues were.

These dyes work by binding to specific proteins on the outside and inside of the cell. If the cell is alive, the dye will react with proteins on the outside membrane and glow a fluorescent green. If the cell is dead, these dyes will be able to pass through the cell membrane and react with other proteins withinthe cell, tuning it bright red. Of the 10 tissue samples collected from 8 patients, 9 glowed green, meaning the cells were alive and could be used to test cancer treatment options.

The scientists treated each living specimen with 4 of the most common immunotherapy treatments for melanoma. They allowed the treatment and immune cells to interact for 3 days at body temperature, and then used the same staining techniques to see how effective each cancer drug was. They compared how many organoid cells were killed when treated with the cancer drug and how many were killed without treatment by looking at the dead (red) and green (alive) organoids. If most or all of the cells were killed only when treated with a certain drug, they predicted that this treatment would be effective inside the patient. Of the 7 patients with viable tissue samples, this technique was able to predict if each therapy would be effective in 6 of the cases (85%).

These scientists emphasize that while the number of patients used in the study was relatively small, it does show the potential for further investigation and even application in some hospitals. They were later able to create viable cell systems with appendix cancer cells that are ready to be tested using these techniques, which shows that these methods could be applied to other forms of cancer.

The authors of the paper also discuss possible cooperation between these experimental techniques and genetic profiling. The two ideas could work in unison, with genetic profiling predicting the probable effective treatments and these techniques testing each possible combination. With the growth in genetic medicine, combined with advances in biomaterials science, cancer patients could start to see a truly personalized approach to treatment.

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Simulating cancer patients' organs in the lab to test treatments - Sciworthy

ALAMEDA, Calif.--(BUSINESS WIRE)--Scribe Therapeutics Inc., a molecular engineering company creating the most advanced technologies for CRISPR-based genetic medicine, today announced its participation in the Goldman Sachs The New Guard: Privates Leading The Disruption In Healthcare conference.

Benjamin Oakes, CEO and co-founder of Scribe Therapeutics, will join the Gene Editing: Moving from Molecular Scissors to Pencils panel on Thursday, April 7, 2022 at 10 a.m. ET in New York, NY.

About Scribe Therapeutics

Scribe Therapeutics is a molecular engineering company focused on creating best-in-class in vivo therapies that permanently treat the underlying cause of disease. Founded by CRISPR inventors and leading molecular engineers Benjamin Oakes, Brett Staahl, David Savage, and Jennifer Doudna, Scribe is overcoming the limitations of current genome editing technologies by developing custom engineered enzymes and delivery modalities as part of a proprietary, evergreen platform for CRISPR-based genetic medicine. The company is backed by leading individual and institutional investors including Andreessen Horowitz, Avoro Ventures and Avoro Capital Advisors, OrbiMed Advisors, Perceptive Advisors, funds and accounts advised by T. Rowe Price Associates, Inc., funds managed by Wellington Management, RA Capital Management, and Menlo Ventures. To learn more about Scribes mission to engineer the future of genetic medicine, visit http://www.scribetx.com.

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