Treating childhood allergies with gut bacteria
Australian biotech company Ondek is on a mission to develop an immunotherapy based on the gram-negative bacterium Helicobacter pylori — previously known as Campylobacter pylori — which it hopes to eventually deploy as a new treatment for childhood allergy.
As noted by Ondek Chairman Peter Hammond, there has been “a dramatic rise in the prevalence of allergic diseases” over the past few decades.
“According to the World Allergy Organization, an estimated 30% to 40% of the global population suffered from some form of allergic condition in 2011,” Hammond stated.
This so-called ‘allergy epidemic’ has been linked by various experts to increased hygiene and reduced exposure to microorganisms in childhood, termed the ‘hygiene hypothesis’. As explained by Ondek founder Professor Barry Marshall, a world authority on H. pylori, “[when] children aren’t exposed to enough infectious or non-infectious bacteria, the immune system can get ramped up”.
“They then can become more reactive to all kinds of new proteins in their diet or susceptible to pollen in the air,” Professor Marshall said.
In 1982, Professor Marshall and Dr Robin Warren were responsible for the discovery that chronic H. pylori infection can trigger the development of stomach ulcers. It was a breakthrough that revolutionised the medical management of these ulcers and helped to generate a cure — and subsequently won the two researchers the 2005 Nobel Prize for Medicine and Physiology.
“Dr Warren saw bacteria in the stomach when he was checking biopsies for stomach cancer,” Professor Marshall recalled. “He could see inflammation [gastritis] but did not really make a connection with bacteria initially. I was interested in answering the question of ‘how do bacteria survive in the acid stomach?’; therefore, we were really exploring the wonders of bacteria and, as a side effect, discovered that these bacteria were the cause of peptic ulcers and probably gastric cancer.”
About half of the world’s population is currently infected with H. pylori, according to the World Health Organization, with the bacterium surviving in the human stomach by modulating the host’s immune system. But while 10% of people with long-term infection will develop an ulcer and have an increased risk of stomach cancer, the vast majority carry the bug without developing any symptoms. In fact, H. pylori appears to be beneficial for the development of a healthy immune system, with several independent studies having shown an inverse correlation between the presence of H. pylori and the incidence of allergic disorders such as eczema and asthma.
It all began in 2008, when New York researchers published what they claimed to be “the first [study] to report an inverse association between H. pylori seropositivity and asthma in children” in The Journal of Infectious Diseases. Since then they have been joined by researchers from Switzerland to Israel, all of whom have come to the same conclusion: the risk of developing allergy is reduced in the presence of infection with H. pylori.
“H. pylori is a potent immune modulator,” explained Dr Jenny Harry, CEO of Ondek. “It acts to suppress a hypersensitive immune system and thereby reduce a person’s response to an allergic challenge, eg, exposure to pollen or peanuts. This modulatory action has a greater effect when the immune system is developing, ie, in infants or young children. Consequently, young children exposed to H. pylori have a lowered risk of becoming allergic.
“The impact of this is significant when we consider that approximately 50% of the kids that present with eczema — the earliest sign of allergy — will proceed to develop a food allergy or allergic asthma later in life.”
Now Ondek is utilising Professor Marshall’s prize-winning insights to create a H. pylori-based drug to rebalance the human immune system and improve the treatment of common allergies. The aim is to release a product that will downregulate hypersensitive allergic responses, with the main ingredient of the new product harnessing the immune modulatory properties of H. pylori.
“The wider medical community is recognising the important role of the microbiome in regulating the immune system,” Professor Marshall said. “H. pylori is a unique member of the natural gut microbiome and has a potent immune regulatory function.
“In the 21st century, as H. pylori is disappearing, humans in response have become hyperreactive to environmental allergens. If we put H. pylori back in a safe way, we can move allergic people back into a normal range.”
The company has already patented a killed derivative of H. pylori to be developed as a natural and safe immunotherapy called ImmBALANCE, which has been in development for the past four years and is being formulated as a dry powder which can be presented as tablets or capsules or dissolved in drinks.
“Children could put it in a drink and, over the course of a few months, suppress their allergic response,” Professor Marshall noted.
“By developing an oral product which contains non-viable H. pylori, we can get the immune advantages that Stone Age man used to get by having live bacteria, with none of the disadvantages.
“It won’t depress your immune system; it will just take the edge off.”
Back in 2013, Ondek received a $919,596 development grant from the National Health and Medical Research Council (NHMRC) to support the clinical development of ImmBALANCE. Four years later, the company is on a high after recently receiving $3.59 million in equity funding from investors looking to support the development of the new allergy treatment.
The company’s business strategy is to develop ImmBALANCE through to clinical proof of concept before partnering with a global pharmaceutical firm that has the capacity to complete clinical development and take the product to international markets. The target indication is childhood eczema, as the Ondek team believes the product will be most effective during the development of the immune system during infancy and childhood. It will also be tested against existing allergies and other chronic inflammatory diseases in adults.
“Capital raised will be prudently deployed to scale up manufacturing of the new drug compound and generate preclinical safety and efficacy data ahead of a meeting with the US Food and Drug Administration (FDA) later next year to seek guidance and permission to start regulatory toxicology studies and human trials,” said Dr Harry.
Ondek will be looking to trial ImmBALANCE in humans within two to three years.
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