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
July 9,2020

Washington, Jul 9: Ayurvedic practitioners and researchers in India and the US are planning to initiate joint clinical trials for Ayurveda formulations against the novel coronavirus, the Indian envoy here has said.

In a virtual interaction with a group of eminent Indian-American scientists, academicians, and doctors on Wednesday, Indian Ambassador to the US Taranjit Singh Sandhu said the vast network of institutional engagements have brought scientific communities between the two countries together in the fight against Covid-19.

 “Our Institutions have also been collaborating to promote Ayurveda through joint research, teaching and training programs. Ayurvedic practitioners and researchers in both the countries are planning to initiate joint clinical trials of Ayurvedic formulations against Covid-19,” Sandhu said.

“Our scientists have been exchanging knowledge and research resources on this front,” he said.

The Indo-US Science Technology Forum (IUSSTF) has always been instrumental in promoting excellence in science, technology, and innovation through collaborative activities.

To address Covid-19-related challenges, the IUSSTF had given a call to support joint research and start-up engagements. A large number of proposals are being reviewed on fast track mode by the experts on both the sides, he said.

“Indian pharmaceutical companies are global leaders in producing affordable low-cost medicines and vaccines and will play an important role in the fight against this pandemic,” Sandhu said.

According to the ambassador, there are at least three ongoing collaborations between Indian vaccine companies with US-based institutions.

These collaborations would be beneficial not just to India and the US, but also for the billions who would need to be vaccinated against Covid-19 across the world, he noted.

Asserting that innovation will be the key driver in pandemic response and recovery, he said tech-companies and start-ups have already begun to take the lead in this direction.

"Telemedicine and telehealth will evolve as will other digital platforms across sectors," he said.

Noting that there has been a longstanding collaboration between India and the US in the health sector, he said scientists have been working together in several programs to understand important diseases at the basic and clinical level.

Many such programs have been focused on translational research to develop new therapeutics and diagnostics.

There are over 200 ongoing NIH funded projects in India involving 20 institutions from NIH network and several eminent institutions in India engaged in a wide spectrum of research areas to create health care solutions, the senior diplomat said.

The collaboration under Vaccine Action Program (VAP) resulted in the development of ROTAVAC vaccine against rotavirus which causes severe diarrhea in children.

The vaccine was developed by an Indian company (Bharat Biotech) at an affordable cost. It has been commercialised and introduced in the Expanded Program on Immunisation.

Development of many other vaccines such as TB, Influenza, Chikungunya are also in progress under the VAP, he said.

 “As I speak, the VAP meeting is in progress where experts from both countries are deeply engaged in technical discussions to expedite development of Covid-19 vaccine,” Sandhu said in his remarks.

During the interaction, the eminent experts appreciated India's handling of the Covid-19 pandemic and offered their valuable suggestions and best practices in this regard.

They shared their ideas on deepening the knowledge partnership between India and the US.

The experts who took part in the interaction, were drawn from wide-ranging fields including artificial intelligence, quantum information science, biomedical engineering, robotics, mechanical engineering, earth and ocean science, virology, physics, astrophysics, and health sciences.

Prominent among those who attended the virtual interaction were Subhash Kak Regents Professor at Oklahoma State University, Dr Vijay Kuchroo, Samuel L Wasserstrom Professor of Neurology at Harvard Medical School, Dr Ashish M Kamat, Professor of Urology at MD Anderson Cancer Center, Ashutosh Chilkoti, Alan L Kaganov Professor of Biomedical Engineering and Chair of the Department of Biomedical Engineering at Duke University; and Prof Manu Prakash, a professor in Department of Bioengineering at Sandford University, among others.

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Dr G K Sudhakar Reddy
August 4,2020

Being overweight or obese is now recognised as a serious cause of ill health and disability. There is a significant positive association between orthopaedic disorders and the level of obesity causing pain, deformity and difficulty in walking.

Excess body weight accumulation increases pressure on joints, particularly the hips, knees and ankles.

Here are a few type of  arthritis:

Osteoarthritis

It is a condition of damage/ wear and tear of the joint lining or cartilage. Obesity triggers this by loading excessive weight on the weight bearing joints like the knee and the hip. 

Knee Osteoarthritis

This is the most common arthritis especially in the Indian subcontinent.

While walking, an individual exerts 3 to 6 times pressure that of the body weight on the weight-bearing knee joint, which means in an obese with excess body weight, larger forces are exerted, which lead to higher risk of deterioration of cartilage.

In addition, there are excessive fat tissues that produce hormones and other factors that affect the joint cartilage metabolism and cause inflammation of the joints giving rise to joint pathology.  Leptin is one of the hormones causing knee osteoarthritis. 

Hip osteoarthritis

The force exerted across the hip is 3 times that of body weight. Hip osteoarthritis is caused by factors such as joint injury, increasing age and being overweight.    

Hand osteoarthritis

The observation that obese individual has a higher risk in having hand osteoarthritis has led to a hypothesis that the metabolic effect produced by fat tissue is the underlying factor. 

Osteoporosis

It is a progressive bone condition of decrease in bone mass and density (Bone Mineral Density or BMD) which can lead to an increased risk of fracture. Recent research suggests that obesity may accelerate bone loss. It is the amount of muscle mass which is seen in an active person, which accounts for bone strengthening effects and not due to the fat seen in a heavy person.

Low back pain

Low back pain from degenerative disc disease of the lumbar spine is one of the most disabling conditions in the community and overweight and obesity have the strongest association with seeking care for low back pain.

Managing Hip and Knee Osteoarthritis

Life style changes

If one is overweight, try to lose weight by doing more physical activity and eating a healthier diet. Regular exercise keeps you active and mobile and builds up muscle, thereby strengthening the joints and can improve symptoms. 

Pain Killers

Painkillers help with pain and stiffness for short term. They don’t affect the arthritis itself and won’t repair the damage to your joint. Creams and gels can be applied directly onto painful joints.

Nutritional Supplements

Glucosamine and chondroitin are nutritional supplements. Animal studies have found that glucosamine can both delay the breakdown of and repair damaged cartilage. However, there is insufficient evidence to support the use of glucosamine in humans and one can expect only a mild-to-moderate reduction in pain

Joint injections

If pain from osteoarthritis is severe joint steroid injections are injected into the joints that can reduces swelling and pain. The injections can start working within a day or so and may improve pain for several weeks or months. 

Hyaluronic acid injections, which help to lubricate your knee joint also give short term relief. In early stages. Stem cell treatment or cartilage regeneration procedures are being tried in young people with small defects, however it is still experimental and lacks long term evidence.

Surgery

May be recommended if you have severe pain or mobility problems.

Arthroscopy

If one has frequent painful locking/stiffening episodes especially in the knee joint, an operation to wash out loose fragments of bone and other tissue as joint can be performed by a minimally invasive key hole procedure called Arthroscopy.

Arthrodesis

If hip or knee replacement is not suitable, especially in young people who do heavy manual work, one can consider an operation known as an arthrodesis, which fuses your joint in a permanent position. This means that your joint will be stronger and much less painful, although you will no longer be able to move it.

Osteotomy

In young, active people in whom a knee joint replacement would fail due to excessive use one can consider an operation called an osteotomy. This involves adding or removing a small section of bone either above or below your knee joint.  This helps realign your knee so your weight is no longer focused on the damaged part of your knee. An osteotomy can relieve your symptoms of osteoarthritis, although you may still need knee replacement surgery eventually as you grow old

Joint replacement surgery

Joint replacement therapy is most commonly carried out to replace hip and knee joints. It involves replacing a damaged, worn or diseased joint with an artificial joint made of special plastics and metal.

For most people, a replacement hip or knee will last for at least 20 years, especially if it is cared for properly and not put under too much strain.

Dr G K Sudhakar Reddy is a Sr Consultant Orthopaedic Surgeon at Citizens Speciality Hospitals, Hyderabad

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Agencies
April 21,2020

The Lockdown is not a cure but a critical strategy to prevent the geographical spread of COVID-19.

While pandemics at this level involves actual life threatening situations for individual's or significant others in one's immediate circle, it envisages a marked disruption in routine life. Even after the pandemic has been contained and will come to pass; it's aftermath will leave a trailblazer which demands planning and implementation of a post pandemic reconstruction of society with potentially traumatic experiences varying in intensity, multiplicity and duration.

Degree of Trauma

It would do well for each one of us to realise that the pandemic is "potentially traumatic", since not everyone will experience COVID -19 as a traumatic event in their lives. Yet, there will be those who may develop post pandemic stress reactions, depression and related dysfunction and pathological reactions while still other exhibit healthy reactions to the same set of circumstances.

"Psychological reactions to the pandemic can be distilled into four distinct prototypical patterns, namely, Resilience, Recovery, Chronic and Delayed patterns which may vary in intensity, multiplicity, and duration. Resilient individual have an ability to bounce back from adversity and experience modest or little disruption in normal functioning and are able to maintain a relatively stable, healthy levels of psychological functioning even after enduring the pandemic. Recovery pattern is characterised by relatively rapid reduction in symptoms and return to normal functioning whereas chronic pattern is characterised by symptoms and dysfunction of a long duration," says Pune-based military psychologist Lt Col Dr Samir Rawat.

Challenges at the Individual and Community Levels

From a psychological perspective, post pandemic reconstruction would entail catering to the problems, concerns and needs of those adversely impacted by the COVID -19 with stress symptoms typically characterised by individual's experiencing an overwhelming trauma of the pandemic (for example, recurring nightmares/ breaking into a cold sweat, flashback of stressful events, increasing irritability, low frustration tolerance or emotional numbing).

It could also manifest in depressive symptoms which may result in lack of interest or diminished pleasure in activities and things which you earlier liked to do, feelings of worthlessness or even survivor guilt in case of a loss of a loved one due to COVID-19, fleeting thoughts of death and suicidal ideation. Physical symptoms, on the other hand could be a decrease in appetite, weight and sleep problems, inability to focus and lack of concentration.

Undoubtedly, the pandemic will cause a financial loss of varying magnitude to many, especially the marginalised and economically disadvantaged strata of daily wage earners; it will also lead to loss of jobs (already beginning to show), homelessness, occupational difficulties and new challenges in interpersonal relations at work and on the home front, besides physical health problems and psychological barriers with new norms of accepted social behaviour (social distancing, handshakes, an obsession for cleanliness to name a few).

Emotional battles

Many factors may influence whether individuals come out stronger and more resilient or surrender to the pandemic. Emotion Regulation is one such long term critical factor that can play an important role in contributing to varying degrees of adaptation with negative or positive outcomes. While we know that primary emotions are fear, anger, disgust, joy, anticipation, acceptance, sadness and surprise, other basic emotions include wonder, love, desire, joy, hatred, sadness, attachment, disgust, rage and even expectancy .

To be able to regulate these emotions and avoid negativity , especially on social media platforms is likely to increase efforts in emotion regulation which involves initiating, increasing or maintaining an emotional response.

This means by regulating or on the other hand by stopping, decreasing or avoiding an emotional response, that is, by down-regulating, depending on the individual's objectives and goals or his /her ability to regulate emotions in the valued and given direction.

"One of the best ways to regulate emotions is through cognitive restructuring wherein we change the way we think; after all it is not the event but the interpretation of the event which is perceived as stressful and finding meaning promotes resilience and reduces risk and vulnerability to stress," advises Dr Rawat.

Adding, "Clearly, we need to have a psychological plan to prevent, mitigate and minimise negative outcomes by post pandemic reconstruction of society at an individual and community level all over the country; this has to be integrated by all leaders across verticals in diverse domains."

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