Fruit Flies in Drug Discovery: Faster, Cheaper, Smarter Early Screening

In the UK, biotech companies are facing pressure with the rising costs of developing new drugs alongside low approval rates of Phase I clinical trials [1, 2]. Yet the early stages of drug discovery still rely on mammalian models like mice, which can be slow, expensive and difficult to scale [3]. As a result, they are increasingly becoming a bottleneck, especially for new ventures entering the market [4].

One of the most effective ways to test potential drugs in the early stages is using the fruit fly, Drosophila melanogaster, which is becoming more popular due to yielding faster results, as seen in a recent review [5, 6, 7]. For example, researchers used fruit flies to test a group of diabetes drugs (DPP4 inhibitors, that reduce human blood sugar) and found that the DPP4 enzyme in flies works very similarly as in humans, as flies showed reduced glucose levels and better insulin-like signalling [7].

Many companies have also used flies in their research:

• Genentech developed a drug called Vismodegib, used to treat basal-cell carcinoma, through mapping Hedgehog signalling in Drosophila [8].
• Denali targets LRRK2 in Parkinson’s using a DNL151 inhibitor and is currently being evaluated in clinical trials, a pathway that had been studied using Drosophila LRRK2 models [9, 10]
• Biogen formed a Consortium in 2012 to identify ALS drug targets, where Spyros Artavanis-Tsakonas’s research on behalf of Biogen, at Harvard University, has discovered the Phospholipase D pathway to be a potential therapeutic target in 2020 [11, 12].

Why Fruit Flies Are a Better Alternative

Mammalian studies remain essential in drug development since regulatory bodies still require it, but they can be a major barrier in early stages, especially when a single mouse study can take up to weeks or even months [3, 11]. Many compounds are shown to also fail after expensive mammalian studies, meaning that businesses waste valuable time and capital to reach no success [4].

Fruit flies are relatively cheap to keep and breed, having a 10-12 day life cycle, so they reproduce rapidly [5]. Researchers can also access thousands of validated fly strains through platforms like FlyBase, which links directly to global stock centres - this makes it far easier and cheaper to run early in-vivo screening compared with mice [14].

Unlike simple cell cultures, flies are full living animals that can provide quick findings on toxicity, absorption, behaviour, and survival [15, 16]. This helps eliminate weak or unsafe candidates from the start, before deciding if further tests should be done on more expensive mammalian models if needed [16].

Moreover, despite being small insects, flies share many genes and biological pathways with humans, especially in: neurodegeneration, cancer signalling, metabolic regulation, and developmental pathways [17, 18].

Overall, research has shown that fruit flies can successfully highlight potential drugs to combat diseases ranging from Parkinson’s and Alzheimer’s to cancer and immune disorders. This makes them a highly effective, versatile tool for early drug discovery [19, 20].

AI-Imaging Has Transformed What Flies Can Do

Ten years ago, fly studies relied heavily on manual observations, such as basic video tracking [21]. Today, as shown in recent case studies, AI-driven imaging allows high-throughput, automated analysis, showing that:

• thousands of flies can be tracked automatically
• subtle movements can be quantified
• lifespan and phenotypes can be measured precisely
• AI can remove human bias with highly-objective results [22, 23, 24].

For example, a recent paper described a system called a Hatching-Box: and imaging and tracking system that automatically monitors and behaviour of flies over their life-cycle, across many vials simultaneously [22]. Another example is the recent development of FlyVISTA, a machine-learning video-imaging system that quantifies misbehaviours and responses, such as sleep, in freely-moving flies [20]. This shows how the field is pushing towards advanced systems to monitor and phenotype flies, so businesses can collect early-stage data at a fraction of the time and cost of mammals, and produce reliable data.

Strategic Takeaways

For start-ups and smaller biotech firms, integrating Drosophila early in the drug-discovery pipeline can offer clear advantages in the pharmaceutical industry:

• saving costs: early screening of large numbers of compounds in flies costs much less than in mammals [4]
• efficiency: results come faster, as researchers can quickly test which drug candidates are most promising [5]
• higher chance of success: by filtering out poor candidates earlier (i.e. for toxicity, poor absorption, no effect), companies lower the risk of costly failures later with only higher-quality candidates entering mammalian studies [17]
• exploring new areas: flies allow for testing diseases that are difficult or expensive to study using other models, making them useful for companies working on multiple, diverse targets [6]
• From an investment perspective, pipelines that use fruit flies show efficient use of resources, faster progress, and smarter early decisions - qualities that are attractive to both investors and partners [25].

References

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