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Gene therapy helps combat some forms of blindness – and ongoing clinical trials are looking to extend these treatments to other diseases

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Gene therapy helps combat some forms of blindness – and ongoing clinical trials are looking to extend these treatments to other diseases

New gene therapies are helping to treat certain forms of inherited blindness.
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Jean Bennett, University of Pennsylvania

An estimated 295 million people suffer from visual impairment globally. Around 43 million of those people are living with blindness. While not every form of blindness can be cured, recent scientific breakthroughs have uncovered new ways to treat some forms of inherited blindness through gene therapy.

Jean Bennett is a gene therapy expert and a professor emeritus of ophthalmology at the of Pennsylvania. She and her laboratory developed the first gene therapy drug for a genetic disease to be approved in the U.S. The drug, Luxturna, treats patients with biallelic RPE65 mutation-associated retinal dystrophy, a rare genetic disorder that causes visual impairments and blindness in patients early in .

In March, Bennett spoke at the 2023 Imagine Solutions Conference in Naples, Florida, about what gene therapy is, why it matters and the she and her team have had helping the blind to see. caught up with Bennett after the conference. Her edited answers are below.

Jean Bennett speaks at the 2023 Imagine Conference.

What is gene therapy and how does it work?

Gene therapy is a set of techniques that harness DNA or RNA to treat or prevent disease. Gene therapy treats disease in three primary ways: by substituting a disease-causing gene with a healthy new or modified copy of that gene; turning genes on or off; and injecting a new or modified gene into the body.

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How has gene therapy changed how doctors treat genetic eye diseases and blindness?

In the past, many doctors did not think it necessary to identify the genetic basis of eye disease because treatment was not yet available. However, a few specialists, me and my collaborators, identified these defects in our research, convinced that someday treatment would be made possible. Over time, we were able to create a treatment designed for individuals with particular gene defects that lead to congenital blindness.

This development of gene therapy for inherited disease has inspired other groups around the world to initiate clinical trials targeting other genetic forms of blindness, such as choroideremia, achromatopsia, retinitis pigmentosa and even age-related macular degeneration, all of which lead to vision loss. There are at least 40 clinical trials enrolling patients with other genetic forms of blinding disease.

Gene therapy treatments are now available in pharmacies and operating rooms all over the world.

Gene therapy is even being used to restore vision to people whose photoreceptors – the cells in the retina that respond to light – have completely degenerated. This approach uses optogenetic therapy, which aims to revive those degenerated photoreceptors by adding light-sensing molecules to cells, thereby drastically improving a person's vision.

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You created one of the first gene therapies approved in the US. What is the current state of the clinical use of gene therapy?

There are now many approved gene therapies in the U.S., but the majority are combined with cell therapies in which a cell is modified in a dish and then injected back into the patient.

Woman in lab coat, face mask, goggles and gloves squeezes syringe into petri dish
Many forms of gene therapy are helping to treat blindness.
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The majority of those therapies target different forms of cancer, although there are several for devastating inherited diseases. The drug Skysona is a new injectable gene therapy medication that treats boys ages 4 to 17 with cerebral adrenoleukodystrophy, a genetic disease in which a buildup of very-long-chain fatty acids in the brain can lead to death.

The gene therapy that my team and I developed was the first FDA-approved project involving injection of a gene therapy directly into a person – in this case, into the retina. Only one other FDA-approved gene therapy is directly administered to the body – one that targets spinal muscular atrophy, a disease that causes progressive muscle weakness and eventually death. The drug, Zolgensma, is injected intravenously into babies and children diagnosed with the disease, allowing them to as healthy, active children.

There are now more than two dozen FDA-approved cell and gene therapies, including CAR T-cell therapies – in which T cells, a type of immune system cells, are modified in the laboratory to better attack cancer cells in the body – and therapies for various blood diseases.

What are you currently working on that you're most excited about?

I am very about some upcoming clinical trials that my team will soon initiate to target some other devastating blinding diseases. We will incorporate a new test of functional vision – how your eyes, brain and the visual pathways between them work together to help a person move in the world. This test utilizes a virtual reality that is not only fun for the user but promises to an objective measure of the person's functional vision. I hope that our virtual reality test will inform us of any potential benefits from the treatments and also serve as a useful outcome measure for other gene and cell therapy clinical trials involving vision.

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What are the biggest challenges gene therapy faces?

The biggest challenges involve systemic diseases, or diseases affecting the entire body rather than a single organ or body part. For those diseases, super-high doses of gene therapy reagents must be delivered. Such diseases involve not only technical challenges – such as how to manufacture enormous amounts of gene therapy compounds without contaminating them – but also difficulties ensuring that the treatment targets diseased tissues without causing toxic immune side effects. That level of a problem does not exist with the eye, where relatively small doses are used and exposure to the rest of the body is limited.

Another challenge is how to address diseases in which the target gene is very large. Current approaches to delivering treatments into cells lack the capacity to hold large genes.

Cost remains a key issue in this effort – gene therapy drugs are enormously expensive. As drug manufacturers are able to refine this technique, gene therapy drugs may become more commonplace, causing their price to drop as a result.The Conversation

Jean Bennett, Professor Emeritus of Ophthalmology; Cell and Developmental Biology, University of Pennsylvania

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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How does the brain think?

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theconversation.com – Jennifer Robinson, Professor of Psychology, Auburn – 2024-05-06 07:34:55

Thinking builds neural networks, which is why practice improves performance.

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Jennifer Robinson, Auburn University

Curious Kids is a series for children of all ages. If you have a question you'd like an expert to answer, send it to curiouskidsus@theconversation.com.

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How does the brain think? – Tom, age 16, San Diego, California


Have you ever wondered how your brain creates or why something randomly popped into your head? It may seem like magic – but actually the brain is like a supercomputer inside your head that helps you think, learn and make decisions.

Imagine your brain as a busy with lots of streets and buildings. Each part of the brain has a specific job to do, just like certain of a city or certain buildings serve different purposes. When you have a thought, it's like a message traveling through the city, passing from one area to another.

As a professor of psychology and neuroscience, I have studied the brain for almost 20 years. Neurologists, neuroscientists and neurosurgeons work every day to understand the brain better. And there's still a lot to learn.

Your brain has four major compartments, and each compartment has lots of “buildings.”

Practice and repetition create skills

The neuron is a key player in the brain – these are tiny cells that send and signals and messages so they can communicate with each other.

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Your brain has somewhere between 80 billion and 100 billion neurons. Neurons tend to group together to form neural tracts, which would be like the streets and highways in the city analogy. When you have a thought, neurons in your brain fire up and create electrical impulses. These impulses tend to travel along similar pathways and release tiny chemicals called neurotransmitters along the way.

These neurotransmitters are like the construction crew that builds the roads, making it easier for the messages to be delivered. You can imagine it as a dirt road, but as more traffic – that is, neuron signals – travel the dirt road, the road gets upgraded to a paved street. If the traffic continues, it gets upgraded to a highway.

As you learn new things and experience the world around you, these connections grow stronger. For example, when you are learning to ride a bike, you may be unsteady and find it hard to coordinate all of the different muscles along with your ability to balance. But the more you practice, the more the neurons controlling your muscles and your ability to balance fire together, which makes it much easier as you practice. Neurons are wiring together and forming neural networks.

That's why practice and repetition are important for improving your skills, whether playing the piano or learning a language. Neural networks are created and then strengthened the more times they communicate together. Scientists have a saying in this field: “Neurons that fire together wire together.” Certain thinking or behavior patterns can be chalked up to this kind of repeated synchronized activity.

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Developing creativity

You are conscious of only a very small portion of the information your brain takes in. It is constantly receiving input from your senses – sights, sounds, tastes, smells and touch. When you see a cute puppy or hear your favorite song, your senses send signals to the brain, triggering a chain reaction of thoughts and emotions.

The brain also stores memories, which are like files in a computer that you can access whenever you need them. Memories shape your thoughts and influence how you see the world.

If you remember a fun day at the beach, it might make you feel happy and relaxed. If you smell an apple pie, it may remind you of your grandma's baking. These thoughts are triggered because these pleasant associations have been formed in your brain, and through repetition, strengthened over time.

Creativity is another superpower of the brain. When you let your imagination wild, your brain can up with new ideas, stories and inventions. Artists, writers and scientists all use their creative brains to explore new possibilities and solve problems.

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Have you ever experienced a “eureka” moment when a brilliant idea pops into your head out of nowhere? That's your brain's way of connecting the dots and coming up with a solution.

Walnuts, leafy greens, chickpeas and berries are on the list of brain foods.

Keeping your brain healthy

Most scientists agree that sleep is really important for your brain to information from the day and to allow it to rest and form new connections. A lot of people find that they have new ideas or thoughts after a good night's sleep. The opposite is true, too – without enough sleep, you may feel like you can't think straight.

Along with enough sleep, eat healthy foods and exercise. Just like a car needs fuel to run smoothly, your brain needs nutrients and oxygen to function at its best and to boost your thinking power.

Activities that challenge you are also great: reading, doing , playing music, making art, doing math, writing essays and book reports and journaling. Positive thinking also helps. Keep in mind that whatever you are consuming – what you're eating or what you're watching, listening to or reading – has the power to influence your brain.

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Conversely, smoking cigarettes, vaping, drinking alcohol and using drugs kills brain cells. So might head injuries that can occur when playing sports such as football, soccer and bicycling – but wearing a helmet can make a big difference.

The brain is a fascinating organ that works tirelessly to create thoughts, memories and ideas. As technology continues to improve, scientists will learn more and more about how biological processes give rise to our conscious experiences. The challenges of learning about the brain are like a neuroscientific moonshot – we have a long way to go before we completely understand how it works.


Hello, curious kids! Do you have a question you'd like an expert to answer? Ask an adult to send your question to CuriousKidsUS@theconversation.com. Please tell us your name, age and the city where you live.

And since curiosity has no age limit – adults, let us know what you're wondering, too. We won't be able to answer every question, but we will do our best.The Conversation

Jennifer Robinson, Professor of Psychology, Auburn University

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Animal behavior research is getting better at keeping observer bias from sneaking in – but there’s still room to improve

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theconversation.com – Todd M. Freeberg, Professor and Associate Head of Psychology, of Tennessee – 2024-05-03 07:16:49

What you expect can influence what you think you see.

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Todd M. Freeberg, University of Tennessee

Animal behavior research relies on careful observation of animals. Researchers might spend months in a jungle habitat watching tropical birds mate and raise their young. They might track the rates of physical contact in cattle herds of different densities. Or they could record the sounds whales make as they migrate through the ocean.

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Animal behavior research can fundamental insights into the natural processes that affect ecosystems around the globe, as well as into our own human minds and behavior.

I study animal behavior – and also the research reported by scientists in my field. One of the challenges of this kind of science is making sure our own assumptions don't influence what we think we see in animal subjects. Like all people, how scientists see the world is shaped by biases and expectations, which can affect how data is recorded and reported. For instance, scientists who in a society with strict gender roles for women and men might interpret things they see animals doing as reflecting those same divisions.

The scientific corrects for such mistakes over time, but scientists have quicker methods at their disposal to minimize potential observer bias. Animal behavior scientists haven't always used these methods – but that's changing. A new study confirms that, over the past decade, studies increasingly adhere to the rigorous best practices that can minimize potential biases in animal behavior research.

Black and white photo of a horse with a man and a small table between them displaying three upright cards.

Adding up?

Karl Krall/Wikimedia Commons

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Biases and self-fulfilling prophecies

A German horse named Clever Hans is widely known in the history of animal behavior as a classic example of unconscious bias leading to a false result.

Around the turn of the 20th century, Clever Hans was purported to be able to do math. For example, in response to his owner's prompt “3 + 5,” Clever Hans would tap his hoof eight times. His owner would then reward him with his favorite vegetables. Initial observers reported that the horse's abilities were legitimate and that his owner was not being deceptive.

However, careful analysis by a young scientist named Oskar Pfungst revealed that if the horse could not see his owner, he couldn't answer correctly. So while Clever Hans was not good at math, he was incredibly good at observing his owner's subtle and unconscious cues that gave the math answers away.

In the 1960s, researchers asked human study participants to code the learning ability of rats. Participants were told their rats had been artificially selected over many generations to be either “bright” or “dull” learners. Over several weeks, the participants ran their rats through eight different learning experiments.

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In seven out of the eight experiments, the human participants ranked the “bright” rats as being better learners than the “dull” rats when, in reality, the researchers had randomly picked rats from their breeding colony. Bias led the human participants to see what they thought they should see.

Eliminating bias

Given the clear potential for human biases to skew scientific results, textbooks on animal behavior research methods from the 1980s onward have implored researchers to verify their work using at least one of two commonsense methods.

One is making sure the researcher observing the behavior does not know if the subject from one study group or the other. For example, a researcher would measure a cricket's behavior without knowing if it came from the experimental or control group.

The other best practice is utilizing a second researcher, who has fresh eyes and no knowledge of the data, to observe the behavior and code the data. For example, while analyzing a file, I count chickadees taking seeds from a feeder 15 times. Later, a second independent observer counts the same number.

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Yet these methods to minimize possible biases are often not employed by researchers in animal behavior, perhaps because these best practices take more time and effort.

In 2012, my colleagues and I reviewed nearly 1,000 articles published in five leading animal behavior journals between 1970 and 2010 to see how many reported these methods to minimize potential bias. Less than 10% did so. By contrast, the journal Infancy, which focuses on human infant behavior, was far more rigorous: Over 80% of its articles reported using methods to avoid bias.

It's a problem not just confined to my field. A 2015 of published articles in the sciences found that blind protocols are uncommon. It also found that studies using blind methods detected smaller differences between the key groups being observed to studies that didn't use blind methods, suggesting potential biases led to more notable results.

In the years after we published our article, it was cited regularly and we wondered if there had been any improvement in the field. So, we recently reviewed 40 articles from each of the same five journals for the year 2020.

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We found the rate of papers that reported controlling for bias improved in all five journals, from under 10% in our 2012 article to just over 50% in our new review. These rates of still lag behind the journal Infancy, however, which was 95% in 2020.

All in all, things are looking up, but the animal behavior field can still do better. Practically, with increasingly more portable and affordable audio and video recording technology, it's getting easier to carry out methods that minimize potential biases. The more the field of animal behavior sticks with these best practices, the stronger the foundation of knowledge and public trust in this science will become.The Conversation

Todd M. Freeberg, Professor and Associate Head of Psychology, University of Tennessee

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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A look inside the cyberwar between Israel and Hamas reveals the civilian toll

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theconversation.com – Ryan Shandler, Professor of Cybersecurity and International Relations, Georgia Institute of Technology – 2024-05-03 07:16:12
The conflict between Israel and Hamas is online as well as on the ground.
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Ryan Shandler, Georgia Institute of Technology; Daphna Canetti, University of Haifa, and Tal Mimran, Zefat Academic College

The news about the Israel-Hamas war is filled with reports of Israeli families huddling in fear from relentless rocket attacks, Israeli tanks and artillery flattening buildings in the Gaza Strip, hundreds of kidnapped hostages imprisoned in subterranean tunnels, and millions of people driven from their homes by fighting.

But beyond the visceral violence lies a hidden layer of the war – an online conflict. We are scholars of cyberwarfare who have cataloged and analyzed the various cyber operations conducted during the war by Hamas, Israel and other nations and hacking groups supporting one side or the other. The data paints a picture of an unseen facet of the conflict, and it offers insights about the nature of cyber conflict more broadly.

The main conclusion we've drawn is that the consequences of cyber conflict are primarily felt by civilians, not the soldiers or militants actively engaged in the fighting. We find that the cyberattacks inflict on digital is far less significant than the resulting harm to humans, and the resulting upward spiral of violence.

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Hamas' cyberwarfare activities

The cyberattacks Israeli and civilian systems have had mixed effects. Some technically simple attacks succeeded in obtaining crucial intelligence that assisted Hamas fighters' incursion into Israel. Other attacks employed a scattershot approach, targeting anything within digital reach – hospitals, universities, banks and newspapers. These attacks didn't serve any military purpose, but simply aimed to disrupt Israeli life and terrorize the public.

The quantity and sophistication of the attacks have made clear that hackers working for the government of Iran, a key Hamas funder and supplier, are supporting Hamas' online warfare. Other “hacktivists” and private hacking groups based in countries as varied as , Pakistan and Russia have also joined the fray.

Before the deadly Oct. 7, 2023 terror attack on Israel that sparked the current war, Hamas cyber operatives were working to support the attack planning. A Hamas hacking unit called Gaza Cybergang spied on Israel in search of sensitive information about Israeli military installations. The information they gleaned was instrumental during the attack.

Hamas hackers also conducted phishing attacks, relatively simple attacks in which fake email or text messages resemble legitimate ones and encourage a user to either reply with sensitive information or click on a link that downloads malicious software to their computer or mobile phone.

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As the Oct. 7 attack unfolded, the pro-Palestinian hacktivist group AnonGhost released a mobile app with the same name as a prominent reputable app that gives Israeli citizens warnings about impending attacks from Hamas into Israel. AnonGhost issued false alerts – including, reportedly, one about a nuclear attack – and collected users' data, including their contacts, call logs and text messages.

However, since full-fledged hostilities erupted, Hamas has been largely unable to carry out effective cyberattacks that aid its war efforts. As a result, the group turned to information warfare, seeking to evoke panic and shift public opinion.

The most common type of attack that Hamas' cyberwarriors and their allies use now is a distributed denial-of-service, when a barrage of nonsense internet traffic is aimed at one or more websites, email servers or other internet-connected systems. They get overwhelmed by the nonsense traffic and either shut down or cease to function properly.

Denial-of-service attacks have hit websites for news outlets, banks, financial institutions and government agencies. One attack took the Jerusalem Post website offline for two days. The group that claimed responsibility for that attack was a religious hacktivist group called Anonymous Sudan, with known connections to Russian hacking groups.

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Hamas and its online allies are also using wiper malware, which infects a computer and destroys its data. This kind of attack does not serve a purpose such as extortion or surveillance – it just aims to destroy everything in its wake.

We also recorded several attacks that infiltrated databases and released their contents, such as one where the private data of students at Ono Academic College was published online.

Another of attacks took control of digital billboards to display the Palestinian flag in sites around Israel, along with false news about military defeats. These attacks are part of a broader misinformation effort designed to shape domestic debate and terrorize Israeli civilians.

A billboard reads 'Hacked' and contains a pro-Palestinian message.
Electronic billboards have been hacked to display pro-Palestinian messages around the world, including this one in Spain.
Horacio Villalobos/Corbis via Getty Images

Israel's activities

By contrast with Hamas, Israel is a global cyber power whose military possesses some of the strongest cyber warfare capabilities in the world.

Yet the effectiveness of Israel's cyber arsenal is limited because Hamas doesn't depend on the internet very much. Without any targets to strike on a digital battlefield, Israel's primary strategy has been to turn on or off internet connectivity in Gaza. It can do this because Israel controls the electricity and internet cables that serve Gaza.

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On Oct. 27, 2023, Israel imposed a near-total telecommunications blackout that lasted for approximately 34 hours. The telecommunications blackout was condemned by international organizations, including the World Health Organization, whose director general posted that the blackout made it “impossible for ambulances to reach the injured.” Without internet or telephone connections, Palestinians in Gaza can't call an ambulance, nor can medical staff stay connected with their dispatch centers.

Similar internet shutdowns have occurred frequently since then. Due to damage, displacement and power and internet disruptions, internet connectivity in Gaza has been reduced to 15% of the typical rate.

During periods when there was internet service in Gaza, pro-Israeli hacktivists got involved. For example, the group WeRedEvils crashed the Gaza Now news site. As hostilities intensified, up to 60% of all traffic to Palestinian websites was made up of denial-of-service attack traffic, according to Cloudflare, a U.S.-based data-transfer and tracking company. The bulk of the attacks were aimed at banks and technology companies.

The U.S. is involved, too. The federal Cybersecurity and Security Agency is working with the Israelis to help thwart some cyberattacks.

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A few observations about online conflict

In contrast to Hollywood depictions of cyber warfare, where unstoppable hackers can cripple entire armies and countries with the push of a button, the reality of cyber power is more constrained. Digital battles cannot win wars. Most of the online operations in the Israel-Hamas war have little effect on the actual battlefield. They involve spying or propaganda, not wholesale destruction.

Our data shows that cyber warfare doesn't necessarily give terror groups the ability to face major powers on more equal terms. Hamas' online operations have not been able to offset Israel's military superiority. But Israel's online capabilities are not a significant advantage against a largely offline opponent.

Perhaps most importantly, though, is our recurring finding that civilians are the foremost victims of cyberattacks during war. In our experiments, conducted among more than 10,000 people over 10 years, we have seen that cyberattacks arouse severe psychological distress – akin even to the harm generated by physical terrorism. When confronted with cyberattacks, people feel trapped and anxious, and their sense of safety plummets. As a result, victims lash out and demand strong retaliation in a way that fuels cycles of violence.

As Israel and Hamas volley cyberattacks back and forth, innocent people are caught in the crossfire. This human dimension of cyber warfare is the threat that worries us.The Conversation

Ryan Shandler, Professor of Cybersecurity and International Relations, Georgia Institute of Technology; Daphna Canetti, Professor of Political Science, University of Haifa, and Tal Mimran, Associate Professor of International Law, Zefat Academic College

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