Australian scientists have identified the mechanism linking malaria in pregnancy to low birth weight babies.
Researchers from the Burnet Institute and the University of Melbourne believe the discovery could enhance the hopes of survival in the 85 million pregnancies exposed to malaria globally every year.
Philippe Boeuf, the lead researcher on the study, said that placental malaria is a major cause of low birth weight, which is a major risk factor in 80 per cent of neonatal deaths.
Children born at a low weight are also at a higher risk of intellectual development issues and are more susceptible to chronic diseases such as diabetes in adulthood.
"Before now, no one understood the link between being infected with malaria in pregnancy and having an increased risk of delivering a low birth weight baby," Boeuf said in a media release on Wednesday.
"But we've identified the first mechanism that links the two, and this gives us the opportunity to try to improve fetal growth, and therefore, birth weight.
"Because low birth weight is the main cause of neonatal death, if we improve the birth weight, this could have a significant impact on neonatal survival, and allow a healthier adult life."
The researchers discovered that inflammation caused by malaria disrupts the mTOR signalling pathway which impairs the placenta's capacity to deliver amino acids, a major factor in foetal growth, to the foetus.
The discovery of mTOR inhibition gives scientists the opportunity to supplement the pathway, restroing its activity to normal, Boeuf said.
"There have been quite a few trials of nutritional supplementation of malaria-exposed pregnant women that had relatively modest impact on birth weight. We think that's because those interventions haven't been targeted specifically at mTOR," Boeuf said.
"The view of most of these interventions has been, well, these women and/or their fetuses are not getting enough nutrients, therefore if we give mothers dietary supplements, that should improve birth weight, but results have largely been inconsistent.
"The approach we are taking is, OK, we know that mTOR inhibition appears to be a driver of low birthweight, so let's research ways to activate mTOR, and those that show any effect, we'll take further and hopefully to implementation."
This malaria drug is having an amazing effect on brain cancer patients
There's new hope for improved brain cancer treatments after scientists noticed unexpectedly positive effects coming from an unlikely source – a drug normally used to treat malaria.
The anti-malaria drug chloroquine has now been used as a last resort on three brain cancer patients, and in each case, it seems to have overcome the cancer's resistance to traditional treatments.
Chloroquine appears to break down the defences that tumours develop in response to cancer-fighting drugs by effectively 'resetting' their vulnerability to treatment.
"We have treated three patients with the combination, and all three have had a clinical benefit," says paediatric oncologist Jean Mulcahy-Levy from the University of Colorado.
"It's really exciting - sometimes you don't see that kind of response with an experimental treatment."
One of the patients is 26-year-old Lisa Rosendahl, who was previously given just a few months to live. The aggressive glioblastoma in her brain had become resistant to chemotherapy and other targeted treatments.
Rosendahl was eventually put on a cancer inhibitor called vemurafenib, but as often happens with that particular drug, the tumour in her brain soon adapted to become resistant to it, too.
That led the staff working on Rosendahl's case to try a different approach - targeting a separate cellular process called autophagy.
Autophagy is a normal process inside the body whereby dead or damaged cells are removed and recycled to make way for fresh ones. Taken from Greek, the term literally means "to eat oneself", and it's an important way of detoxifying and repairing the body.
The trouble is, tumours sometimes use autophagy to stay healthy, leveraging cellular recycling to withstand the stress that drugs put them under. Rosendahl had a type of cancer that was especially dependent on the process, due in part to a genetic mutation called BRAFV600E.
Fortunately, chloroquine is known to inhibit autophagy, so with that in mind, Mulcahy-Levy and her team decided to give the drug a try as a last-ditch effort to combat the tumours - by combining it with vemurafenib.
"Miraculously, [Rosendahl] had a response to this combination," says Mulcahy-Levy. "Four weeks later, she could stand and had improved use of her arms, legs, and hands."
The chloroquine didn't remove the tumour, but it did weaken the cancer's defences enough to get the vemurafenib drug working again to do that on its own, and now Rosendahl's quality of life is improving.
Only three patients have been given the treatment so far, and not every type of cancer relies so much on autophagy, so until it's been tested on a much larger and diverse sample, it's too soon to tell if it will have similar effects on other patients.
But the team says a wider clinical test could be rolled out quickly, because chloroquine is already approved as a safe anti-malaria drug by the US FDA (Food and Drug Administration).
The researchers hope that future studies will reveal other cancers where this treatment could be effective.
"It makes me feel really lucky to be a pioneer in this treatment," says Rosendahl. "I hope it helps and I hope it helps people down the road. I want it to help."
The latest findings have been published in eLife.
Synthetic protein offers hope of malaria cure
Of the serious diseases transmitted by the mosquito, malaria is one of the most common and dangerous, killing hundreds of thousands of people each year. Now, scientists have developed a synthetic protein which not only completely cures malaria in mice, but also prevents the disease from recurring down the track.
According to the World Health Organization (WHO), malaria was responsible for an estimated 438,000 deaths last year. Initially, symptoms seem flu-like, including nausea, fever, headaches and sore joints and muscles, but things get worse if left untreated, and could eventually end in death.
"There are drugs available that treat malaria, but emerging drug-resistance is becoming an increasing problem, especially in parts of South-East Asia," said Dr. Michelle Wykes, head of the Molecular Immunology laboratory at QIMR Berghofer Medical Research Institute in Australia. "Vaccines that are being trialed generally only protect against some species of malaria parasite, and they don't protect people in the long-term. This means that we urgently need new treatments."
Research conducted at the Institute may have uncovered a new solution. A certain protein helps the immune system fight off infection, but advanced malaria tends to suppress that protein. Realizing this, the team synthesized their own version of it.
"Within the immune system, there are dendritic cells, which are the generals of the immune army, and there are T cells, which are the soldiers," Wykes explained. "The dendritic cells tell the T cells when to attack an infection and when to put down their weapons."
For that job, the dendritic cells use proteins on their surface, including one that instructs the T cells to switch off. But another, called PD-L2, is able to override those instructions, ordering the T cells to keep fighting the good fight.
"We found that when humans and mice are infected with severe malaria, levels of PD-L2 decrease and so the T cells aren't being told to keep fighting the parasites," said Wykes. "We don't know how malaria manages to block the production of PD-L2. But once we knew how important this protein was for fighting the disease, we developed a synthetic version of it in the laboratory."
To test it out, the researchers infected mice with a lethal dose of malaria, before administering three doses of their synthetic protein. All of them were cured. In addition, when the same mice were reinfected with the parasites five months later, the infection couldn't take hold so a further dose of the synthetic protein wasn't necessary.
"This would be a completely new way of treating malaria by stimulating a person's own immune system to destroy the parasites," Wykes said.
The research was published in the journal Immunity.