Monthly Archives: July 2022

Irvine, Calif., July 14, 2022 The role of gene alterations resulting from childhood adversity in adults addicted to heroin and a search for blood tests to predict addiction vulnerability are part of sweeping research that scientists are launching at the University of California, Irvine.

The nearly $3.5 million five-year project to understand the opioid crisis is a collaboration of the School of Biological Sciences and the School of Medicine, as well as the Irvine Center for Addiction Neuroscience. The National Institute on Drug Abuse is funding the work through an initiative to encourage research innovation.

Researchers will examine how early-life adversity influences epigenetics, or experience-induced changes in gene expression, and how they affect the likelihood of adult addiction.

We want to see how these epigenetic alterations interact with the heroin experience and if there are sex differences in these processes, said lead principal investigator Stephen Mahler, associate professor of neurobiology & behavior and a fellow in the Center for the Neurobiology of Learning and Memory.

For example, what happens upon using opioid drugs might be different between people who had scarcity of resources or chaotic environments as children and those who didnt, Mahler said. This could account for why some people become addicted to these drugs, while others dont.

He noted that earlier research shows opioid-addicted women were more likely than men to have experienced stressful circumstances as children, such as those resulting from growing up amid early-life adversity.

Examining the bloods capacity for revealing the propensity for addiction and other mental disorders is also part of the study. This work centers on extracellular vesicles, which are cell-produced droplets containing proteins and microRNAs. Researchers will compare these vesicles in blood samples and cerebral spinal fluid of rodents to learn if those in the blood hold clues about an individuals risk of addiction or other mental disorders. If so, it could mean blood screening can provide information about the brain that helps prevent and treat addiction and related conditions.

Gaining a better understanding of an individuals epigenetics and brain activity opens up powerful new possibilities, said Mahler. As an example, if someone suffers a broken leg and it is determined they are susceptible to addiction, they can be given an alternative treatment for pain. For people already dependent on opioids, we may be able to develop precise treatments that target the genetic activity causing the addiction.

Numerous other inquiries will also take place as part of the research project. Serving as principal investigators are Christie Fowler, associate professor of neurobiology & behavior and fellow, CNLM; Vivek Swarup, assistant professor of neurobiology & behavior; and Dr. Tallie Z. Baram, distinguished professor of pediatrics, anatomy & neurobiology and neurology, Danette Shepard Professor of Neurological Sciences, and fellow, CNLM. Marcelo Wood, professor of neurobiology & behavior and fellow, CNLM, is co-investigator.

Nearly 50,000 people nationwide died from opioid-related overdoses in 2019, according to the National Institute on Drug Abuse. It calls opioid misuse and addiction a serious national crisis that affects public health as well as social and economic welfare.

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About UCIs Brilliant Future campaign:Publicly launched on Oct. 4, 2019, the Brilliant Future campaign aims to raise awareness and support for UCI. By engaging 75,000 alumni and garnering $2 billion in philanthropic investment, UCI seeks to reach new heights of excellence instudent success, health and wellness, research and more. TheSchool of Biological Sciences and School of Medicine play a vital role in the success of the campaign. Learn more by visiting https://brilliantfuture.uci.edu/school-of-biological-sciences/ andhttps://brilliantfuture.uci.edu/uci-school-of-medicine/.

About the University of California, Irvine:Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities and is ranked among the nations top 10 public universities byU.S. News & World Report. The campus has produced five Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 224 degree programs. Its located in one of the worlds safest and most economically vibrant communities and is Orange Countys second-largest employer, contributing $7 billion annually to the local economy and $8 billion statewide.For more on UCI, visitwww.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visit news.uci.edu. Additional resources for journalists may be found at communications.uci.edu/for-journalists.

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What gene changes and blood could tell us about the opioid crisis - UCI News

Written by: James Carnell

Dr. Nirmalya Saha

If all the DNA molecules that make up a single person were lightbulbs, epigenetic modulators would be the light switch. While it is factual that our DNA plays a large role in our personal makeup, overall health, and body functionality, the picture is much more complex. Even while in utero, developing fetuses can experience epigenetic changes that play a major role in what that future persons makeup will be. While many of these changes are a normal part of development and will continue to happen over time, epigenetic modulators can also trigger internal changes that are linked to serious diseases, such as cancer.

As a molecular biologist, Dr. Nirmalya Saha has dedicated his career to understanding the role epigenetic changes play in Leukemia and how these complex factors present themselves throughout the course of specific cancers. While his work is largely focused on the oncology space, Dr. Saha recognizes just how powerful epigenetics can be. If these light switches can cause disease in an otherwise healthy person, they might just be the secret to fighting a disease once it has become a reality.

Dr. Sahas Impact on the Epigenetics Space

Though the importance of epigenetics is becoming more widely known, often emphasized by new studies and medical research advancements, many professionals in the molecular biology field have begun to examine its role in certain body functions. For Dr. Saha, the focus has been on developing an understanding of how important the epigenetic regulator PRMT5 is in Acute Myeloid Leukemia as well as unpacking the dynamic between SETDB1 and suppressing Leukemia. These studies are about more than understanding a complex relationship; they are about finding a solution for diseases that take lives.

Acute Leukemia with MLL rearrangement makes up about 5-10% of cases in adults and a shocking 70% of cases in infants. This disease straps those affected with a devastating prognosis and low chances of survival. With Dr. Sahas research, its becoming more likely that science can create a novel inhibitor molecule to treat the disease and offer patients a better outlook. Even if his work stopped here, with this subset of patients, it would be extraordinary, but it goes much further.

The Future of Epigenetics

Epigenetic therapies can fight against many forms of cancer, completely revolutionizing the toolkit doctors and patients have access to when battling different types of the disease. If these therapies are effective for one subset of diseases, there is so much potential to develop similar therapies for a plethora of disease categories. The work Dr. Saha and other molecular biologists are doing right now will be the difference between a future patient living and dying, growing old to see their families flourish or being taken too soon.

Aside from treating diseases, epigenetics plays a large role in understanding how each body works on an individual level, almost providing a fingerprint of each person. Armed with this knowledge, epigenetic researchers are making leaps and bounds in the space of personalized medicine. If we can determine how a persons body will react to different factors, its possible to mitigate potential dangers and get ahead of medical problems before they even start.

The Future of Dr. Saha

Though he has already provided astounding research, advancing the molecular biology field and propelling medical capabilities, Dr. Saha does not seem to be slowing down. As his research uncovers more powerful information, he is reminded of why he started this career to begin with: to help people.

Today, Dr. Saha is a committed teacher and mentor, working in the Department of Pathology at the University of Michigan, Ann Arbor. His work has been featured in renowned publications such as BBA-Reviews on Cancer, Stem Cell Reports, and BMC Genomics. As an active member of the American Association of Cancer Research and the Sigma Xi Honor Society, Dr. Saha will continue on his path to saving lives through research.

This article does not necessarily reflect the opinions of the editors or management of EconoTimes

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Epigenetics Is The Key To Treating Complex Diseases; Dr. Nirmalya Saha Is Using It To Unlock Cancer Treatment And More - EconoTimes

This summer, huge swaths of the U.S. have already faced record-breaking heat waves. Heat kills more people than any other extreme weather event, and deadly heat waves are getting longer and hotter as the climate warms.

Staying cool and informed is essential. So we spoke with Thomas Clanton, a professor of applied physiology and kinesiology at the University of Florida and an expert in the effects of heat on the body, about how to recognize heat illness and the long-term consequences of this kind of stress.

Heatstroke is a medical emergency. If you notice signs of heatstroke in a person, call 911 immediately.

It's a really broad spectrum. At the lowest end is heat exhaustion, and on the more extreme end we have heatstroke. The difference is really the presence of neurological symptoms in heatstroke. Throughout the spectrum, mild to severe injury to liver, heart, kidney and muscle can be present. So, you can have heat exhaustion and you're probably still thinking pretty well, but you know you're hot. You try to get out of the heat and you're functional. However, heatstroke victims can go unconscious, lose motor control or become delirious, so their ability to respond is limited.

Clinically, a person would be diagnosed with heatstroke if they have a temperature above 40 degrees centigrade (104 degrees Fahrenheit) and also exhibit central nervous system symptoms.

Other signs that people notice include pallor (paleness) of the skin. Whereas profuse sweating is a normal reaction to heat, at the extremes of heatstroke the sweat response doesn't work as well, and the skin can become dry. If you begin to notice these signs, get into the shade, drink plenty of water and move to a reclined position. If ice bags or wet towels are available, place them under the arms, on the neck and along the groin regions. If any unusual neurological symptoms develop, get medical assistance immediately.

A lot of times people in the heat exhaustion range may not know they are getting heat illness. I think that's one of the concepts worth emphasizing. Besides just feeling hot, an individual may feel a little woozy or just not themselves. When this occurs, and they are not well hydrated, they can move quickly to conditions of heatstroke. Heatstroke can develop rapidly and it often mistaken for just normal overheating and exhaustion, so it pays to be aware of the clinical symptoms and to act quickly.

Absolutely. A buddy can get help, call the ambulance, right? And you can help each other stay healthy. Coaches can play this role during workouts and team players up. I play golf in the summer, and my partner and I make sure each other drinks plenty of water and stays in the shade whenever possible. We bring wet towels for our shoulders. These techniques are really effective and pretty simple.

We rightfully worry about people dying from heatstroke. But the evidence in the last few years is extremely good that some people who experience heatstroke may have medical consequences that can affect them the rest of their life.

The field has documented changes in the immune system of humans and animals years after a heatstroke. Heatstroke victims also have a greater frequency of developing chronic heart disease and kidney diseases later in life.

In the animals I study,we see evidence of epigenetic changesthat likely explain some of these long-term effects. Epigenetics is kind of cellular memory. So at a cellular level, cells have their own way of remembering if they've been exposed to severe stresses in the environment, which can help them respond over time by altering their cellular responsiveness. Cells imprint this memory by using enzymes that chemically tag their DNA. This memory is often helpful and can be adaptive, but can also be maladaptive if the stress is severe.

We certainly see strong epigenetic signals in the hearts, immune cells and skeletal muscle of mice one month after heatstroke. The mice look fine, their hearts look fine, but later they begin to develop metabolic disorders and other secondary effects. We believe that many of these epigenetic changes are maladaptive and make the animals less able to withstand additional stresses in their environment or to fight off other chronic forms of disease. Once we understand this in our animal models, we hope to develop approaches in humans that will help them ward off the development of these long term consequences to severe heat exposures.

Eric Hamilton July 18, 2022

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Heatstroke stresses the body years after the original heat illness - University of Florida

CAMBRIDGE, Mass., July 14, 2022 /PRNewswire/ -- Omega Therapeutics, Inc. (Nasdaq: OMGA) ("Omega"), today announced that it has received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1/2, first-in-human, clinical study of OTX-2002 for the treatment of hepatocellular carcinoma (HCC). OTX-2002, an Omega Epigenomic Controller (OEC), is designed to downregulate c-Myc (MYC) expression pre-transcriptionally through epigenetic modulation while potentially overcoming MYC autoregulation.

"We are thrilled to obtain clearance to advance OTX-2002 into the clinic and are excited about the prospects of what this new class of medicines may mean for patients in need," said Mahesh Karande, President and Chief Executive Officer of Omega Therapeutics. "This is an important milestone for our company, representing our first program to receive FDA clearance to enter the clinic and the first ever clinical trial to evaluate an epigenomic controller. This new class of programmable mRNA therapeutics leverages our groundbreaking science and has broad potential applicability in many therapeutic areas."

About OTX-2002

OTX-2002 is a first-in-class Omega Epigenomic Controller in development for the treatment of HCC. OTX-2002 is an mRNA therapeutic delivered via lipid nanoparticles (LNPs) and is designed to downregulate MYC expression pre-transcriptionally through epigenetic modulation while potentially overcoming MYC autoregulation. The MYC oncogene is associated with aggressive disease in up to ~70% of patients with HCC. An IND application for OTX-2002 has been cleared by the FDA.

About Omega Therapeutics

Omega Therapeutics, founded by Flagship Pioneering, a clinical-stage biotechnology company pioneering the first systematic approach to use mRNA therapeutics as a new class of programmable epigenetic medicines. The company's OMEGA Epigenomic Programming platform harnesses the power of epigenetics, the mechanism that controls gene expression and every aspect of an organism's life from cell genesis, growth, and differentiation to cell death. Using a suite of technologies, paired with Omega's process of systematic, rational, and integrative drug design, the OMEGA platform enables control of fundamental epigenetic processes to correct the root cause of disease by returning aberrant gene expression to a normal range without altering native nucleic acid sequences. Omega's modular and programmable mRNA medicines, Omega Epigenomic Controllers, target specific epigenomic loci within insulated genomic domains, EpiZips, from amongst thousands of unique, mapped, and validated genome-wide DNA-sequences, with high specificity to durably tune single or multiple genes to treat and cure diseases through Precision Genomic Control. Omega is currently advancing a broad pipeline of development candidates spanning a range of disease areas, including oncology, regenerative medicine, multigenic diseases including immunology, and select monogenic diseases, including alopecia.

For more information, visit omegatherapeutics.com, or follow us on Twitter and LinkedIn

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our product candidate pipeline, including efficacy, trial design, regulatory submissions, approvals and timing thereof, the launch of a clinical trial of OTX-2002 and timing thereof, and the filing of future IND applications and timing thereof. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the novel technology on which our product candidates are based makes it difficult to predict the time and cost of preclinical and clinical development and subsequently obtaining regulatory approval, if at all; the substantial development and regulatory risks associated with epigenomic controller machines due to the novel and unprecedented nature of this new category of medicines; our limited operating history; the incurrence of significant losses and the fact that we expect to continue to incur significant additional losses for the foreseeable future; our need for substantial additional financing; our investments in research and development efforts that further enhance the OMEGA platform, and their impact on our results; uncertainty regarding preclinical development, especially for a new class of medicines such as epigenomic controllers; the fact that our product candidates may be associated with serious adverse events, undesirable side effects or have other properties that could halt their regulatory development, prevent their regulatory approval, limit their commercial potential, or result in significant negative consequences; the impact of increased demand for the manufacture of mRNA and LNP based vaccines to treat COVID-19 on our development plans; difficulties manufacturing the novel technology on which our OEC candidates are based; our ability to adapt to rapid and significant technological change; our reliance on third parties for the manufacture of materials; our ability to successfully acquire and establish our own manufacturing facilities and infrastructure; our reliance on a limited number of suppliers for lipid excipients used in our product candidates; our ability to advance our product candidates to clinical development; and our ability to obtain, maintain, enforce and adequately protect our intellectual property rights. These and other important factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2022, and our other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Contacts

Investor contact: Kevin MurphyArgot Partners212.600.1902[emailprotected]

Media contact: Jason BracoLifeSci Communications646.751.4361[emailprotected]

SOURCE Omega Therapeutics

Link:
Omega Therapeutics Announces FDA Clearance of IND Application for OTX-2002, First Omega Epigenomic Controller, for MYC Driven Hepatocellular Carcinoma...