Have you ever wondered what happens to a newborn's blood in the first weeks of life? Probably not, but researchers at San Raffaele in Milan wondered, and the answer could revolutionize the treatment of blood diseases. During this critical period, the cells that will produce all the blood for the rest of life are still circulating, easily reachable by a simple intravenous injection. It is as if nature had programmed a "moment of positive vulnerability" in which it is possible to correct genetic errors that would otherwise accompany the patient for life. Three different blood diseases have been treated by exploiting this unique biological window. The future of neonatal medicine may have just changed.
A time window that nature keeps open for only a very short time
The discovery ofIRCCS San Raffaele has an almost poetic elegance. While we adults have our blood stem cells tucked away in our bone marrow, protected as if in a safe, newborns go through a special time. In the first few weeks after birth, these precious cells circulate freely in the bloodstream, traveling from the liver to their final destination in the bone marrow.
Italian researchers, led by the team at the San Raffaele-Telethon Institute for Gene Therapy, realized that this represented a unique opportunity. There is no longer any need to laboriously extract stem cells from the marrow, modify them in the laboratory and reintroduce them: a simple intravenous injection is enough to directly reach the target. It's the difference between having to crack a safe and finding the door open.
The scientists tested this approach on newborn mice with three different blood diseases, using modified viral vectors to carry the corrective genes. The results, published in the prestigious journal Cell, show a success rate that in many cases exceeds that of traditional gene therapies. A victory that opens up new scenarios for neonatal medicine.
Three Blood Diseases Defeated Before They Become Incurable
The research targeted three particularly aggressive pathologies. The first is theautosomal recessive osteopetrosis, a condition that prevents the body from producing specialized cells that form bones. Children with this condition develop abnormally fragile bones, and most do not survive the first decade of life.
The second target was a rare metabolic immunodeficiency that severely compromises the immune system. The untreated mice died before weaning, while those that received the gene therapy survived and showed normal health. A result that, if confirmed in humans, could save hundreds of children every year.
But the most impressive success concerns Fanconi's anemia, a bone marrow syndrome caused by defects in DNA repair that primarily affects blood stem cells. This disease is particularly difficult to treat precisely because there are not enough healthy stem cells to collect for traditional gene therapies.. Several months after injection into newborn mice, the production of immune cells had reached normal levels and remained stable for over a year.
Neonatal Medicine: When Timing Makes the Difference Between Life and Death
The key to the success of this approach is perfect timing. Luigi Naldini, director of SR-Tiget and coordinator of the study, explains that there is a “unique, time-sensitive window” during which blood stem cells are abundant in the circulation.
Researchers have shown that this window closes rapidly with age. While neonatal gene therapy works beautifully, in adult mice the efficacy drops dramatically. That’s why they also tested the use of clinically approved “mobilizing” drugs, which force stem cells out of the bone marrow and back into circulation.
The results with these drugs are promising, although less spectacular than those obtained in newborns. It is as if nature had designed this transition period precisely to allow corrective interventions that would otherwise be impossible. A sort of biological “maintenance mode” that remains active only for the first few weeks of life.
As we have already seen in other areas of Italian research, our country is emerging as a world leader in innovative gene therapies. San Raffaele-Telethon has already brought to market gene therapies for ADA-SCID immunodeficiency , metachromatic leukodystrophy, becoming the first non-profit center in the world to produce and distribute drugs for rare diseases.
From basic research to clinical reality
This method does not require futuristic technologies or invasive procedures. The viral vectors used are the same ones already successfully used in other gene therapies, and the intravenous injection technique is routine in any pediatric hospital.
The leap from mice to humans will not be automatic, but the foundations are there. The researchers analyzed human blood samples and confirmed that the same phenomenon occurs in human newborns: a high number of circulating stem cells in the first weeks of life.
Gene therapies are experiencing a moment of extraordinary expansion, and Italy is the protagonist of this revolution. The National Research Center “Development of Gene Therapy and Drugs with RNA Technology”, funded with over 320 million euros by the PNRR, involves 1500 researchers and 32 institutions. An investment that is already bearing concrete fruits.
The road to human clinical trials will still require time and caution, but this research opens up a completely new perspective. Alessio Cantore, one of the authors of the study, clearly underlines this:
“although the efficiency currently remains limited compared to consolidated ex vivo treatments, it could be sufficient, if replicated in human children, to benefit some genetic diseases such as severe immunodeficiencies or Fanconi anemia”.
Neonatal Gene Editing: A Medicine That Looks to the Future
This research is much more than just scientific progress. It is proof that solutions are often hidden in plain sight, in the natural mechanisms that life has developed over millions of years of evolution.
The ability to intervene early in life to prevent diseases that would otherwise last forever has enormous implications. Not just for blood diseases, but potentially for many other genetic conditions that manifest later in childhood or adulthood.
Italian research continues to stand out on the international scene, demonstrating that investing in science and innovation produces tangible results. While other countries focus on more expensive and complex approaches, our researchers have found a more direct path, exploiting a biological feature that had always been there, waiting to be understood and used.
The future of neonatal medicine could be changed forever by this Milanese discovery. And who knows how many other biological “windows” are waiting to be identified and exploited for the good of humanity. Nature, once again, proves to be the best instruction manual we have available: we just need to know how to read it with new eyes.
