Novel imaging approaches show promise for advancing drug discovery. So much promise, in fact, that it’s one of the hot topics up for discussion at this year’s ELRIG’s conferences: Discovery Technologies (26 September 2019) and Drug Discovery (5-6 November 2019). By attending these events, you’ll get expert insights on diverse subjects, including how novel imaging approaches are advancing pre-clinical drug discovery for Central Nervous System (CNS) disorders. Registration is now open, so sign up now for your free place to make sure you don’t miss out on this crucial conversation:

If you can’t wait until then, you can read on to find out more from one of the world-leading authorities in CNS drug discovery: Dr Antti Nurmi, Managing Director of Charles River Discovery Services, Finland. As one of the expert speakers at the upcoming Discovery Technologies conference, Antti gives exclusive insights into how novel imaging approaches could help uncover new treatments for patients affected by neurological diseases.

Overcoming barriers to drug discovery for neurological disorders

Neurological disorders currently affect tens of millions of people worldwide. Sadly, without effective treatments, their prevalence will only continue to rise and in some cases, this will be at an exponential rate. For example, with almost 50 million people already affected by dementia, this number is estimated to double every 20 years, reaching a whopping 131.5 million by 2050.

Aside from the huge consequences that these diseases can have on the quality of life for patients and their families, the economic impact of medication and care for patients is predicted to be astronomical (especially as life expectancy increases worldwide). Indeed, the global cost of dementia  rose above US$ one trillion in 2018.

These are some of the fundamental reasons why Antti and his team is so passionate about studying CNS pathologies and searching for new treatments. “Our vision is to enable better lives for the future and provide patients with medications that can help manage these debilitating conditions,” he explains. “Also, from a personal perspective, when I’m 70 or 80 I don’t want to be relying on my children or care systems—I’m hoping that by then we’ll have effective Alzheimer’s drugs.”

Patching up leaks: Why understanding the brain’s biology is key for successful drug discovery and development

Although we now have some clues about how the brain works, Antti says we still know little about what causes many CNS disorders, particularly at the biological level. This is one key reason why the search for new treatments can be difficult.

In the case of Alzheimer’s disease, for example, much evidence indicates that the β-amyloid protein is an underlying cause because it builds up around brain neurons and eventually kills them. However, drugs targeting β-amyloid keep failing during clinical development. This may be because there are other nonamyloid causes that these drugs aren’t targeting (such as tau protein).

To help reduce the number of late stage failures, Antti emphasizes the need to better understand the basic biological underpinnings of brain disorders before we even start developing any drugs. He is focused on painting a more detailed picture of patients’ brains as well as those of in vivo animal disease models, such as mice. By having a better understanding of brain function in animal models, scientists should be able to more accurately predict the effectiveness of a drug molecule in the clinic.

“It’s helpful to think of the diseased brain as a water tank with many different leaks,” says Antti.  “You can patch one hole up, but this won’t stop all the other leaks or the tank from emptying. That’s the key challenge we face in CNS drug discovery—the drugs we are testing are only patching up one hole. And we don’t even know how many other holes there are or what’s causing the leaks.”

The complexity of the brain and the diseases that affect it is undoubtedly one of the biggest obstacles to overcome in CNS drug discovery. But Antti is determined to find a solution—and it looks like he may have found one.

A vision for the future: The crucial role of imaging in CNS drug discovery and development

Antti’s team is driving forward novel applications of routine clinical imaging tools to pre-clinical testing in CNS drug discovery. He believes that these tools can help uncover a more holistic picture of the brain’s structure and function in in vivo animal models, benefiting drug discovery in the following ways:

  1. Confirming that the animal brain is a suitable model of the disease. That is, by ensuring that what happens in the animal brain is the same (or similar) to what happens in the human brain, you can be more confident that the pharmacological effect of the drug on the animal brain will be the same in humans.
  2. Looking at how the whole brain, or a specific brain region, reacts to the drug.
  3. Measuring the magnitude of brain’s reaction to the drug in real-time.
  4. Easing the translatability of pre-clinical research to the clinic, by using the same imaging techniques to measure both animal and human brains.

One imaging tool that is showing particular promise in pre-clinical drug testing is functional ultrasound (fUS), which is the focus of Antti’s talk at Discovery Technologies 2019. Although ultrasound itself is a well-established imaging technique, having been used to image various organs since the 1940s, its application to pre-clinical studies is something of a novelty.

Applied in the same non-invasive way as clinicians would in humans, fUS is starting to be used to image the brains of animal models in pre-clinical studies. By applying this ‘old’ technique in this new way, it is becoming easier than ever before to track long-term disease progression and pharmacological responses, providing a crucial step towards finding vital drugs for neurological diseases. It also allows to assess steady-state connectivity, i.e. overall functionality of the whole brain or parts of it.

How is functional ultrasound advancing pre-clinical drug discovery?

fUS not only has a high penetration depth for visualization but is also sensitive to parameters such as blood flow and blood-barrier function. Initial studies suggest that fUS is more powerful than magnetic resonance imaging (MRI) because it shows how the brain functions in real-time with better spatial and temporal resolution. What’s more, it gives the same readout for functionality as functional magnetic resonance imaging (fMRI) but without having to anaesthetise the animals, enabling imaging of their brains while they are in their natural, conscious state.

“Functional ultrasound allows you to scan the animal when they are awake without restraints, which means the animal isn’t stressed and the brain is functioning normally,” Antti remarks. “This means you don’t have to worry about how the results from an anaesthetised animal translate into awake patients.”

Consequently, fUS provides a more physiologically relevant image of brain function that can better inform predictions about how a drug will eventually act in a patient. To use Antti’s leaking water tank analogy, fUS could help us form a clearer picture about the ‘leaks’, such as where they are, how many there are, and what’s causing them, which can ultimately help find effective ways of patching them up.

As an early adopter of fUS, Antti’s team has recently validated its use in pre-clinical studies. His talk at Discovery Technologies reveals his research on how fUS can be successfully applied to image brain responses to commonly used psychoactive compounds, as well as in several CNS disease models, including neuropathic pain, stroke, and transgenic animal models.

Seeing the forest: Applying existing tools to uncover the bigger picture

Many different imaging techniques have been applied in routine clinical testing for decades, such as for disease diagnosis and monitoring. It’s only recently that these traditional imaging tools have started to be applied in pre-clinical animal testing, allowing researchers like Antti to advance the field.

Antti remarks that it’s important to start looking for other useful tools and techniques in other fields that could be helpful in CNS drug discovery. “Just focusing on the brain is not enough anymore—we need to look outside neuroscience and take inspiration from other disciplines, because it’s easy to lose sight of the whole forest when you’re only looking at one tree,” notes Antti.

Attending events like Drug Discovery and Discovery Technologies is a fantastic way to see what sort of tools are available and how they could benefit your research. “The ELRIG conferences brings industry and academia together, so we can share knowledge and experiences and find out which emerging technologies will be useful,” Antti says.

Book your free place at ELRIG Drug Discovery and Discovery Technologies

Make sure you book your free place at the upcoming Drug Discovery and Discovery Technologies 2019 conferences today! As the flagship conference, Drug Discovery is the largest event hosted by ELRIG, with an expected 2,000 attendees comprising a diverse audience of drug discovery scientists, exhibitors, the media, investors and educators.

With several world-class speakers at both events, these are unmissable opportunities to get expert insights into the latest developments in drug discovery, including in the ever-burgeoning field of CNS research and imaging.

The events are open to everyone and registration is free. The Drug Discovery conference will be held at the ACC Liverpool on 5-6th November 2019 and the Drug Discovery Technologies will take place at Alderley Park, Cheshire on 26th September 2019. Register now to make sure you don’t miss out on these exciting discussions about the very latest developments in drug discovery.