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The technology could replace the guinea pigs. Report Nyt

The technology could replace the guinea pigs. Report Nyt

The FDA Modernization Act 2.0, signed late last year in the United States, allows drugmakers to collect initial data on safety and efficacy using new high-tech tools, which could one day take the place of laboratory animals . The New York Times article

In 1937, an American pharmaceutical company introduced a new elixir for the treatment of strep throat, unintentionally causing a public health disaster. The product, which had not been tested on humans or animals, contained a solvent which proved to be toxic. More than 100 people died.

The following year, Congress passed the Federal Food, Drug and Cosmetic Safety Act, which required pharmaceutical companies to submit safety data to the US Food and Drug Administration before selling new drugs, helping to usher in the era of drug testing. animal toxicity.

Now a new chapter in drug development could begin. FDA Modernization Act 2.0, signed late last year, allows drugmakers to gather initial safety and efficacy data using new high-tech tools, such as bioengineered organs, organs on chips, and even computer models, instead of animals you live. Congress has also allocated $5 million to the FDA to accelerate the development of alternatives to animal testing.

Other agencies and other countries are taking similar steps. In 2019, the United States Environmental Protection Agency announced it would reduce and eventually eliminate testing on mammals. In 2021, the European Parliament called for a plan to phase out animal testing. writes the New York Times .

According to experts, these initiatives were driven by a number of factors, including the evolution of animal vision and the desire to make drug development cheaper and faster. But what finally makes them feasible is the development of sophisticated alternatives to animal testing.

It is still early days for these technologies, many of which still need to be perfected, standardized and validated before they can be used routinely in drug development. Even proponents of these alternatives acknowledge that animal testing isn't going away anytime soon.

However, experts say there is growing interest in non-animal approaches that could help speed drug development, improve patient outcomes and reduce the burden on laboratory animals.

"Animals are simply a surrogate to predict what will happen in humans," said Nicole Kleinstreuer, director of the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods.

"If we can get to a point where we actually have a fully human-relevant model," he added, "then we don't need the black box of animals anymore."

The behavior of animals

Animal rights groups have been lobbying to reduce animal testing for decades and have found increasingly receptive audiences. In a 2022 Gallup poll, 43% of Americans said medical experimentation on animals was "morally wrong," up from 26% in 2001.

The reduction in animal testing "affects so many people for so many different reasons," said Elizabeth Baker, research policy director at the Physicians Committee for Responsible Medicine, a nonprofit group that advocates for alternatives to animal testing. "Animal ethics is indeed an important factor."

But it's not the only one. Animal testing is time consuming, expensive and prone to shortages. Drug development, in particular, is fraught with failures, and many drugs that look promising in animals are not effective in humans. "We're not 150-pound rats," said Dr. Thomas Hartung, who directs the Johns Hopkins Center for Alternatives to Animal Testing.

Additionally, some new cutting-edge treatments rely on biological products, such as antibodies or DNA fragments, which may have specific targets for humans.

“There is a lot of pressure, not only for ethical reasons, but also for economic reasons and to close the gaps in terms of safety, to adapt to things that are more modern and humanly relevant,” Hartung said.

(Dr. Hartung is the inventor of a Johns Hopkins University patent on the production of brain organoids. He receives royalties from the company that licensed the technology and is a consultant.)

Brave new biology

In recent years, scientists have developed more sophisticated ways to replicate human physiology in the laboratory.

They learned how to coax human stem cells to assemble into a small, three-dimensional cluster, known as an organoid, that has some of the basic characteristics of a specific human organ, such as a brain, lung or kidney.

Scientists can use these mini-organs to study the basis of disease or to test treatments, even on individual patients. In a 2016 study, researchers created mini-organs from cell samples from cystic fibrosis patients and then used the organoids to predict which patients would respond to new drugs.

Scientists are also using 3D printers to produce scaled organoids and to print strips of other types of human tissue, such as skin.

Another approach is based on "organs on a chip". These devices, which are roughly the size of an AA battery, contain tiny channels that can be coated with different types of human cells. Researchers can pump drugs through channels to simulate how they might travel through a particular part of the body.

In a recent study, organ-on-chip biotech company Emulate used a liver-on-chip to test 27 well-studied drugs. All of the drugs passed initial animal tests, but some were later shown to be toxic to the liver in humans. The researchers reported in Communications Medicine last December that the liver-on-chip was able to detect as many as 87 percent of the toxic compounds.

Researchers can also link different systems together, linking a heart-on-chip to a lung-on-chip and a liver-on-chip to study how one drug might affect the entire interconnected system. “I think this is the future,” said Dr. Kleinstreuer.

Calculation of compounds

Not all new instruments require real cells. There are also computational models that can predict whether a compound with certain chemical characteristics is likely to be toxic, how much it will reach different organs, and how quickly it will be metabolised.

Models can be adapted to represent different types of patients. For example, a drug developer might test whether a drug that works in young adults would be safe and effective in older adults, who often have impaired kidney function.

“If you can identify problems as early as possible using a computational model, you avoid going the wrong way with these chemicals,” said Judith Madden, an expert in in silico, or computer-based, chemical testing at the Liverpool John Moores University. (Dr. Madden is also Editor-in-Chief of Alternatives to Laboratory Animals magazine).

Some of these approaches have been around for years, but advances in computer technology and artificial intelligence are making them increasingly powerful and sophisticated, Madden said.

Virtual cells have also shown promise. For example, researchers can model individual human heart cells using "a set of equations that describe everything that happens in the cell," said Elisa Passini, program manager for drug development at the National Center for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), in Great Britain.

In a 2017 study, Dr Passini, then a researcher at the University of Oxford, and her colleagues concluded that these digital cells were better than animal models at predicting whether dozens of known drugs would cause heart problems in humans.

Scientists are now building entire virtual organs, which could be linked together into a kind of virtual man, Dr Passini added, although some of the work is still in an early stage.

In the near term, a virtual lab animal may be more feasible, said Cathy Vickers, head of innovation at NC3Rs, who is working with scientists and pharmaceutical companies to develop a digital dog model that could be used for testing. of drug toxicity.

“It is still very difficult to develop a virtual dog,” Vickers said. “But it's about building this capacity, about creating this momentum.”

Reduce or replace

According to experts, many potential animal alternatives will require further investment and development before they can be used on a large scale. They also have limitations. Computer models, for example, are only as good as the data on which they are built, and more data is available on some types of compounds, cells and outcomes than others.

For now, these alternative methods are better suited to predict relatively simple, short-term outcomes, such as acute toxicity, than complicated, long-term ones, such as the potential for a chemical to increase cancer risk if used for months or years. , the scientists said.

Experts disagree on the extent to which these alternative approaches could replace animal models. “We are absolutely working towards a future where we want to be able to completely replace them,” Kleinstreuer said, while acknowledging it could take decades, “if not centuries.”

But others have said these technologies should be seen as a supplement to and not a replacement for animal testing. Drugs that show promise in organoids or computer models should still be tested in animals, said Matthew Bailey, president of the National Association for Biomedical Research, a nonprofit group that advocates for the responsible use of animals in research. .

"Researchers still need to be able to see everything going on in a complex mammalian organism before they can move on to clinical trials in humans."

However, even this more conservative approach could have benefits, said Nicole zur Nieden, a developmental toxicologist at the University of California, Riverside, who believes total replacement of animal testing is unrealistic.

In particular, according to the expert, the new approaches could help scientists exclude a greater number of ineffective and unsafe compounds before they reach animal testing. This would reduce the number of animal studies researchers have to conduct and limit the chemicals to which laboratory animals are exposed, he added, "We will be able to greatly reduce the suffering of laboratory animals."

(Excerpt from the foreign press review by eprcomunicazione )

This is a machine translation from Italian language of a post published on Start Magazine at the URL on Sat, 18 Mar 2023 06:42:19 +0000.