Gene-editing damages DNA more than thought: study

Agencies
July 17, 2018

Paris, Jul 17:  A revolutionary gene editing technique hailed as the future of disease eradication and mooted for a Nobel Prize may be less precise and cause more cell damage than previously thought, researchers said Monday.

Lab experiments using mouse and human cells revealed that the CRISPR-Cas9 technique "frequently" caused "extensive" gene mutations, a study team reported.

"This is the first systematic assessment of unexpected events resulting from CRISPR-Cas9 editing," said Allan Bradley of the Wellcome Sanger Institute in England, where the team conducts research.

The research showed that "changes in the DNA have been seriously underestimated before now," said Bradley, who co-authored a study published in the journal Nature Biotechnology.

The mutations have not been shown to be harmful, nor benign.

"It is important that anyone thinking of using this technology for gene therapy proceeds with caution and looks very carefully to check for harmful effects," Bradley said in a statement issued by the institute.

First unveiled about six years ago, CRISPR-Cas9 allows scientists to insert, remove and correct a faulty sequence on a strand of DNA in a cell with pinpoint precision.

It has raised hopes that one-day disease-causing genes could be removed or altered before a baby is even born.

In recent years, CRISPR-Cas9 has repeatedly been predicted to win the Nobel Chemistry Prize.

CRISPRs -- clustered regularly interspaced short palindromic repeats -- are part of the immune defence system in bacteria, used to hone in on the exact spot on the genome where the cut should be made.

Cas9 is a protein used as "scissors" to snip through the faulty gene, which is then replaced or fixed by the cell's own DNA repair mechanism.

The technique's safety has not yet been proven, and it is not approved for use in human therapy.

So far, researchers have used it to improve hearing in mice going deaf and to fix a disease-causing mutation in cloned, early-stage human embryos.

But the new finding raises "safety implications," the team said.

They found "large genetic rearrangements such as DNA deletions and insertions" in cells, which could lead to important genes being switched on or off and causing dangerous changes.

The research also showed that standardized tests do not pick up damage to DNA caused by CRISPR-Cas9.

Experts not involved in the study said it was unclear how such large, unintended changes were not noticed before.

But, "the results give no reason to panic or to lose faith in the methods when they are carried out by those who know what they are doing," said Robin Lovell-Badge of The Francis Crick Institute, a biomedical research centre in London.

For Francesca Forzano, a consultant in clinical genetics and genomics with the Guy's and St Thomas' NHS Foundation Trust, the work showed that CRISPR-Cas9 "is much less safe than previously thought" and that safety-monitoring techniques were "not entirely adequate".

More research is needed before any clinical application of the method is considered, said Forzano.

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News Network
February 21,2020

Washington, Feb 21: The fat around arteries may play an important role in keeping the blood vessels healthy, according to a study in rats that may affect how researchers test for treatments related to plaque buildup, as seen in conditions leading to heart attack.

The study, published in the journal Scientific Reports, noted that the fat, known as perivascular adipose tissue, or PVAT, helps arteries let go of muscular tension while under constant strain.

According to the researchers, including Stephanie W. Watts from the Michigan State University in the US, this feature is similar to how the bladder expands to accommodate more liquid, while at the same time keeping it from spilling out.

"In our study, PVAT reduced the tension that blood vessels experience when stretched," Watts said.

"And that's a good thing, because the vessel then expends less energy. It's not under as much stress," she added.

According to Watts and her team, PVAT has largely been ignored by researchers believing its main job was to store lipids and do little more.

Until now, she said, scientists only divided blood vessels into three parts, the innermost layer called the tunica intima, the middle layer called the tunica media, and the outermost layer called the tunica adventitia.

Watts believes PVAT is the fourth layer, which others have called tunica adiposa.

Tunica, she said, meant a membranous sheath enveloping or lining an organ, and adiposa is a synonym for fat.

"For years, we ignored this layer -- in the lab it was thrown out. In the clinic it wasn't imaged. But now we're discovering it may be integral to our blood vessels," Watts said.

"Our finding redefines what the functional blood vessels are, and is part of what can be dysfunctional in diseases that afflict us, including hypertension. We need to pay attention to this layer of a blood vessel because it does far more than we originally thought," she added.

Earlier studies, Watts said, had shown that PVAT plays a role in the functioning of blood vessels, finding that it secretes substances that can cause blood vessels to relax as well as substances that can cause it to contract.

In the current study, the researchers decided to test whether PVAT provides a structural benefit to arteries by assisting the function of stress relaxation.

They tested the thoracic aorta in rats, and found those with intact PVAT had more stress relaxation than those without.

The study revealed that the pieces of artery with surrounding fat had measurably relaxed more than those without.

Watts and her colleagues then tested other arteries, and were able to duplicate the same response.

"It's not something you see only in this particular vessel or this particular species or this particular strain. But that maybe it's a general phenomenon," she said.

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Agencies
May 19,2020

Researchers have found that patients with peripheral artery disease or stroke were less likely to receive recommended treatments to prevent heart attack than those with coronary artery disease. All three are types of atherosclerotic cardiovascular disease.

Depending on the location of the blockage, atherosclerosis increases the risk for three serious conditions: coronary artery disease, stroke and peripheral artery disease.

"Our study highlights the need for public health campaigns to direct equal attention to all three major forms of atherosclerotic cardiovascular disease," said senior study author Erin Michos from the Johns Hopkins University in the US.

"We need to generate awareness among both clinicians and patients that all of these diseases should be treated with aggressive secondary preventive medications, including aspirin and statins, regardless of whether people have heart disease or not," Michos added.

Since atherosclerosis can affect arteries in more than one part of the body, medical guidelines are to treat coronary artery disease, stroke and peripheral artery disease similarly with lifestyle changes and medication, including statins to lower cholesterol levels and aspirin to prevent blood clots.

Lifestyle changes include eating a healthy diet, being physically active, quitting smoking, controlling high cholesterol, controlling high blood pressure, treating high blood sugar and losing weight.

What was unclear was if people with stroke and peripheral artery disease received the same treatments prescribed for those with coronary artery disease.

This study compared more than 14,000 US adults enrolled in the 2006-2015 Medical Expenditure Panel Survey, a national survey of patient-reported health outcomes and conditions, and health care use and expenses.

Slightly more than half of the patients were men, the average age was 65, and all had either coronary artery disease, stroke or peripheral artery disease.

These individuals were the representative of nearly 16 million US adults living with one of the three forms of atherosclerotic cardiovascular disease.

Compared to participants with coronary artery disease, participants with peripheral artery disease were twice more likely to report no statin use and three times more likely to report no aspirin use.

Additionally, people with peripheral artery disease had the highest, annual, total out-of-pocket expenditures among the three atherosclerotic conditions.

The findings showed that participants with stroke were more than twice as likely to report no statin or aspirin use.

Moreover, those with stroke were more likely to report poor patient-provider communication, poor health care satisfaction and more emergency room visits.

"Our study highlights a missed opportunity for implementing life-saving preventive medications among these high-risk individuals," Michos said.

The study was presented in the virtual conference at the American Heart Association's Quality of Care & Outcomes Research Scientific Sessions 2020.

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Agencies
June 28,2020

As the COVID-19 wave sweeps strongly across the country, including in Tamil Nadu, mental health experts say the pandemic has triggered panic attacks among those who tested positive for the virus, causing bouts of depression and even driving some to the brink of suicide.

According to experts, nervousness, fear of contamination, panic attacks, constant reassurance seeking behaviour, sleep disturbance, excessive worry, feelings of helplessness and probability of an economic slowdown are the major factors leading to depression and anxiety among the people.

Potential job losses, financial burden, uncertainty about the future and fears of running out of food and necessities add to the worries.

Online platforms too have seen a growing number of people seeking help for mental health issues, ranging from anxiety and loneliness to concerns over productivity and job loss since the outbreak of COVID-19.

Director of Institute of Mental Health here, Dr R Purna Chandrika said towards April end about 3,632 calls were received and psychiatric counselling was provided to 2,603 callers.

"We have dedicated services at our centres in the districts and the calls meant for government medical college hospitals are routed to the respective institutions," she said.

Due to heavy virus caseloads, making this city the major contributor to the state's tally, the Greater Chennai Corporation too started a free helpline to help residents cope up with stress during the pandemic.

"From the psychological perspective, we don't find a single human being who is not feeling some degree of stress or anxiety due to coronavirus. The intensity and impact varies from person to person," said Lt Col N T Rajan, director of Chennai-based Mastermind Foundation.

The organisation is involved in free counselling throughout India ever since the first case of the deadly virus was reported in the country.

The foundation's recommendation on not to deploy the vulnerable in the police force, especially those above 50 years and women personnel with children below five years for COVID-19 related duty, was accepted and implemented by the Punjab government.

Psychiatrists feel that further worsening situations could lead to severe mental health issues, even triggering suicidal tendencies.

"Further worsening depression may lead to severe mental health issues and suicidal tendencies," said Dr S Senthil Kumar, a psychiatrist.

However, not all of them require medicines, he added.

"The situation is serious. There should be counselling at three stages--on coping with the virus, how to face it if tested positive and how to face life once treated and discharged from the hospital," Rajan said.

Awareness was of paramount importance, he said and warned the pandemic could cause panic attacks while in hospital or drive them to the brink of suicide.

Tamil Nadu, one of the worst affected states with a virus count in excess of 74,000 as of Friday, has witnessed a few instances of suicides allegedly related to COVID-19.

Hari Singh, owner of popular 'Iruttu Kadai' halwa shop in Tirunelveli, allegedly died by committing suicide on Thursday after being tested positive for COVID-19. He was 80.

Earlier in May, two COVID-19 patients in their 50s allegedly committed suicide in separate instances, at the government hospitals they were admitted to for treatment.

In the city corporation limits, a three-member team comprising a psychiatrist, counsellor and a social worker work for the respective zones.

"We direct certain sections of people like those with withdrawal symptoms and people requiring pills, to visit the doctor at their corporation zonal at a specific time, for medicines," a health worker of the civic body said.

Health platform, Lybrate reported an increase of 180 per cent in online patient consultations related to mental health on its platform between March 1 and June 20 across the country.

The largest increase came from Mumbai and Delhi, followed by Pune, Ahmedabad, Chennai and Bengaluru.

The biggest jump was witnessed in the age group of 25 and 45 years.

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