Could llamas help improve our brain health? According to the conclusions of a new original study "made in France" just published in the prestigious journal Nature, The answer is already yes, at least for the mouse.
Based on work by the CNRS, Inserm, and the University of Montpellier, the study focused on schizophrenia, this common neurodevelopmental psychiatric condition (1% of the population) whose causes remain poorly understood – double dependence on genetic and environmental factors – and whose treatments, largely perfectible, are the subject of numerous researches in progress.
“A glutamatergic storm”
As a reminder, in this condition, the occurrence of so-called "positive" symptoms (hallucinations, delirium, agitation) and "negative" symptoms (withdrawal, apathy, depersonalization, etc.) depends on subtle neurobiological mechanisms (excitation, inhibition, modulation, etc.) linked to complex interactions between the different neurotransmitters such as dopamine, serotonin, but also " glutamate, a neurotransmitter used by 80% synapses in our brain", specifies to Science and Future Jean-Philippe Pin, research director at the CNRS (University of Montpellier, Institute of Functional Genomics in Montpellier), one of the signatories of the study.
"At the beginning of the pathology, that is to say generally at the end of adolescence, the excitatory glutamatergic system is particularly affected in schizophrenics, with what is called in English 'glutamatergic storm', the glutamatergic storm, marked by the presence of high glutamate levels in the brain associated with neuronal hyperactivity.", continues the researcher. This is obviously the reason why, in recent years, various research projects have been conducted to develop molecules aimed at regulating these receptors – there are many subtypes – such as mglu2 in particular, known as metabotropic because it has been identified as being able to reduce this glutamatergic storm. But the results to date of the various phase 3 trials have been negative, with too few patients being considered responders., says the scientist. Hence the need to do better.
Read alsoThe feats of precision psychiatry
“A chance discovery by a Belgian team almost 30 years ago”
With this recent work carried out on rodents, the researchers had the idea of changing scale and "trickery" by using antibodies from llamas called "nanobodies" precisely because of their small size. This feature was discovered completely by chance by a Belgian team almost 30 years ago, explains the specialist. Biologists have realized that camelids have the same immune system as us, but that they have, in addition to the specific antibodies from which it is possible to isolate the part that recognizes its target, these nanobodies having a weight of 15 kilodaltons (kDa) instead of 160 kDa. (un dalton corresponding to approximately the mass of a hydrogen atom, editor's note). »
This feature not only makes them easy to produce in the laboratory, but also gives them greater precision in their affinity, which translates pharmacologically into fewer side effects. But above all, these nanobodies can also control the activity of their target, either by activating or inhibiting it.
Antibodies that penetrate the brain
However, one dogma persisted. Despite their small size, they were still considered unable to cross the famous blood-brain barrier (BBB), the collection of cells and blood vessels protecting the brain. However, this dogma has just been shattered because our work demonstrates that they are not only very specific and act quickly and beneficially on the cognitive symptoms of rodents, but also that they cross the BBB and penetrate the brain, persisting there even eight days after a first injection, whether this is given intravenously or intraperitoneally.", explains the researcher.
A delayed action over time which suggests easier use than daily intake, an aspect which is particularly interesting in a condition where it is important to improve patient adherence and avoid therapeutic interruptions.
Obviously, trials will now have to be conducted on patients to confirm these results, and the researchers are already planning to create their own start-up. But our work goes further, predicts Jean-Philippe Pin, because it also opens the door to the development of nanobodies for the treatment of other brain diseases"The llamas will obviously not spit on these potential successes.
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