What is AOX?
Understanding the Alternative Oxidase
Fungi thrive in wildly different environments around the world due to their innate ability to respond to changing conditions. This capacity is due in no small part to a protein enzyme called the alternative oxidase (AOX).
Whenever fungal pathogens face an external threat, such as exposure to fungicidal agents, many of them express the AOX enzyme. AOX provides an alternative respiratory pathway, enabling the fungus to continue respiring and overcome the threat.
Our Chief Scientific Officer, Professor Tony Moore, is an acknowledged world authority on AOX, having dedicated more than 45 years of research to understanding the biology, function and structure of the enzyme. With the work conducted in Professor Moore’s lab at the University of Sussex, we are today able to develop targeted compounds that can prevent the alternative oxidase from functioning and halt the growth of different fungi. A rapidly expanding library of AOX inhibitors is being developed and tested in the search of new development candidates for both clinical and agricultural applications.
Fungicides play a crucial role in protecting crops, with the market for agrochemical fungicides expected to reach $19bn by 2022. Conventional fungicides like azoxystrobin result in plant fungal pathogens expressing AOX and increased potential for developing a resistance. When applied in combination with Alternox Scientific’s AOX inhibitors, this pathway to fungal resistance can be closed off.
Our compounds hold the potential to prevent devastating and irreversable fungal outbreaks across our most important cereal crops – the ‘big 5’ of rice, wheat, maize, potatoes and soybean – which collectively provide more than 60% of the world’s food. By minimising the need for frequent reapplication, we can also reduce environmental damage, protect pollinators and increase crop yields.
Not only do increasingly resilient fungi pose a worldwide threat to food security, but they can also have a devastating effect on regional economies.
In human diseases, AOX plays a key metabolic role in opportunistic human fungal pathogens including candidiasis, cryptococciosis and aspergillosis. Driven by increased hospital infection rates, an ageing population and greater fungal resistance, the clinical antifungal market is predicted to grow to $14bn in 2021.
AlternOx are targeting new antifungal compounds to treat multi drug resistant C. auris infections. C. auris is primarily transmitted nosocomially in ICU settings and, unsurprisingly, the incidence of C. auris has soared in Covid treatment wards where it is estimated that 25% of patients have contracted invasive fungal infections after being treated with immune-suppressing drugs, such as dexamethasone or IL-6 inhibitors.
Similarly, blood stream infections caused by the Candida species (candidemia’s) cause ≥ 82% of all fungal infections with an associated mortality rate of ≥ 40% (Diagn. Microbiol. Infect. Dis.2016) and their resistance to fluconazole, is as high as 78.3%.
The AlternOx development strategy offers the potential of early market entry to treat a ‘niche/orphan’ indication with the longer term potential of a new frontline therapy to treat the much larger candidiasis market.