A Maltese research group has discovered that human blood in space reverts to its foetal type, potentially leading to breakthroughs for thalassaemia patients, whose haemoglobin is dysfunctional after birth and requires a lifetime of transfusions.

Thalassaemic patients have a genetic problem in adult haemoglobin, and if a way to bring their foetal blood back to high levels is found, their symptoms can be improved.

With access to data and blood samples of NASA astronauts, the research group could confirm the adult-to-foetal globin switch in spaceflight and its change back on Earth – a key to unlocking a cure for the millions suffering from the severe hereditary blood condition worldwide and 28 Maltese patients.

Lead author of the study, Joseph Borg, from the University of Malta’s Faculty of Health Sciences, explained that thalassaemia patients, whom he has been studying for decades, have abnormal blood and could do well with elevated levels of foetal haemoglobin, which replaces the role of its deficient adult counterpart.

A key to unlocking a cure for the millions suffering from the severe hereditary blood condition worldwide and 28 Maltese patients

Thalassaemia causes anaemia, resulting in fatigue, weakness, a propensity for other diseases due to immunity and, in severe cases, death. Patients can require blood transfusions every six weeks, a cumbersome treatment that often causes other complications.

“As the name implies, foetal haemoglobin is found in developing foetuses, and this set of genes ‘switches off’ to give way to adult blood,” Borg explained. “Knowing how this switch is controlled – and goes back and forth – is crucial, to say the least,” Borg said.

Historically, the gene switch occurred from foetal to adult blood, so the inflight switch is a unique opportunity to observe it both ways, he continued.

“The plan is to now tease out the key molecules responsible for the switch. We use space to identify the key, and once we hold this, on Earth it can be used to design drugs, molecules and inhibitors to treat the blood disorder.”

While the key has not yet been found, Borg said “we have now chosen a specific road, with no more turns, trial and error, and we know exactly where we are heading. The data is pointing in right direction”.

A possible conclusion is that the microgravity in spaceflight may elicit the mechanisms behind the gene switch. In this environment, astronauts experience a decrease in red blood cells, possibly due to bone mineral density loss, Borg explained.

The question now is why the body and blood of astronauts – healthy adults – ‘feel’ the need to revert to innate foetal genes and expression in microgravity.

“We do not know yet. But that is the next mission,” Borg said.

Mission possible

The research, carried out together with other giants in the academic field, used the space environment to complete another important piece of the puzzle, Borg maintained.

“We had assumed blood would behave differently and that there would be superior levels of foetal haemoglobin in space because this has already been seen in people living in high altitudes and mountains, where oxygen retention is tighter,” he said.

During the pandemic, he read articles about the work on astronauts and reached out to NASA to inquire about their blood levels.

“They said they had never looked at foetal haemoglobin, but they had the data and samples and offered to collaborate.”

The study tapped into the powerful platform made available by NASA’s GeneLab, which provides a wealth of information linking molecular biology and genetics with space medical sciences.

The local research team used the tools and machines in place for Malta’s blood screening programme, set up in 1990, to study the data from NASA, the Japan Aerospace Exploration Agency and private company SpaceX, which manufactures and launches rockets and spacecraft.

It also involved actual blood samples from their respective American, Japanese and private astronauts before, during and after spaceflight.

“Our hypothesis was that there would be elevated levels of foetal haemoglobin and it was proven correct,” Borg said.

Before the end of the year, a number of space missions will be carried out to further the studies, Borg said.

Meanwhile, an ongoing mission, Polaris Dawn, is taking blood from American entrepreneur, pilot and space tourist Jared Isaacman and his three crew members.

These missions involve a five-day trip around the Earth, going up to 500km or higher from its orbit, Borg noted.

Findings would further assist space research to improve the quality of life and safety of astronauts, but they would also be used in “space-for-Earth applications” to make a real difference for patients suffering from blood disorders.

A key player but not the key

The paper, ‘Spatiotemporal Expression and Control of Haemoglobin in Space’, has been published in Nature Communications and quoted in a wide-ranging article in the world’s leading multidisciplinary science journal Nature.

Borg and his colleagues performed the experiments and wrote the paper, with the contribution of Alfred Buħagiar, Josef Borg and Prof. Alex Felice, who, back in the 1990s, pioneered the now well-established field of research on haemoglobin biology.

The study carries on from Maltese scientists’ breakthrough research for a cure for thalassemia in 2010.

Borg had identified a molecule responsible for the switch from foetal to adult haemoglobin that occurs at birth thanks to the discovery of a unique Maltese family, who had high levels of the foetal haemoglobin but did not suffer from thalassaemia.

The hope was that it would get patients to be transfusion independent, but it transpired that locking down this one gene would not be enough to provide a cure.

“It is a key player, but not the key,” Borg said.