How avatars can predict the success of a treatment

Avatar It is a James Cameron film released in 2009 that surely everyone knows because it has the honor of being the highest grossing film in history. otakus You may know that this was the name of a cartoon series about a select few who can manipulate the four elements. Both franchises take their name from a Sanskrit word used in Hinduism to describe the earthly incarnation of a God or spirit, and which has become popular in the 21st century because it is commonly used to designate the representation of a user in the digital world. It is also this idea that has inspired the scientific meaning of the word. avatar to define any system that allows modeling what happens in an organism when it receives a treatment. Medical avatars come in many types, from digital to biological. The most recent, published in an article in Nature A few weeks ago, it is a mini-organ made from patient stem cells that can be used to predict whether or not a new treatment for rare genetic diseases will work.

The idea of using avatars in a clinical context is becoming more and more common, especially to monitor diseases such as cancer, because one of the great problems in medicine has always been how to predict who will or will not respond to a treatment. Humans have sufficiently different physiology that a drug that cures one person may do nothing for another or may even be toxic to a third. The reasons for these varied reactions are complex, and often unknown. So the alternative is to run a simulation that anticipates how the body will respond to a certain chemical compound. And this is where avatars come into play.

Boost thanks to AI

The explosion of artificial intelligence has made it possible to advance the idea of creating digital avatars that recapitulate the behavior of an organism in a computer environment (what is known as digital human modeling). Although they are already beginning to be used, the technology still has important limitations, because the parameters to be controlled to model the behavior of the human body on a biochemical and physiological scale are too numerous. That is why the alternative of creating biological avatars has been used, which already have much of this information incorporated and are a more careful approximation of reality.

To build this type of tools, the essential ingredient is cells, the basic unit of life. But this is not enough: they must be in an environment similar enough to the one they have inside the body so that the reactions are as realistic as possible. This objective can be achieved mainly in two ways: by creating mini-organs (also called organoids) in a culture dish or by inserting human cells into animals (which can range from a mouse to a fly).

Of the first type is the avatar described in Nature by the group of Dr. Scott T. Younger, of the University of Missouri-Kansas, which consists of mini hearts and muscles formed using induced pluripotent cells, very similar to stem cells, generated from the blood of children suffering from Duchenne disease. This is a progressive muscular degeneration of genetic origin that has recently been treated with a gene therapy based on RNA. But the success of the therapy depends on how the patient's cells respond. organoids, which are made of muscle, seem to predict who will benefit from the treatment, since it can be measured how the contraction of the fibers improves.

Despite their usefulness, organoids They are still a primitive, condensed version of an organ and therefore have a limited lifespan as avatars. A more reliable alternative is to use animals to which the patient's cells are transferred. In this case, the advantage is to have an entire organism that provides the implant with an environment similar to that of the human body. In fact, the first clinical trial with avatars made with zebrafish embryos, a species widely used in research, is about to begin in Portugal, led by Dr. Rita Fior, of the Champalimaud Foundation.

Previous experiments have already shown that these fish, which are implanted with malignant cells from a patient, reproduce a patient's response to a treatment for colon cancer in 50 out of 55 cases. They even predict which tumors are most likely to metastasize. Results are obtained in about ten days, which is faster (and cheaper) than what can be done with mice, a kind of model that, in principle, would be biologically closer to us.

Avatars could become an important tool in the development of what has been called personalized medicine, which seeks to find the best treatment for each patient. At the moment, they are expensive and complicated procedures, which is why they are reserved for special situations, but we hope that we will find a way to popularize a strategy that has the potential to greatly improve the effectiveness of treatments while avoiding their side effects.