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Discovering dementia drugs

Cambridge-DDI-Research

By Claire Bromley | Wednesday 05 May 2021

New dementia treatments will change millions of lives for the better. Bringing new hope, to not only the almost one million people living with dementia in the UK, but also their families and friends.

The first wave of treatments came along in the 90’s, thanks to passionate researchers working in the decades before. They have been prescribed to millions of people, helping improve symptoms for some but not attacking the root causes of dementia – diseases like Alzheimer’s.

In June, the FDA approved a new drug for Alzheimer’s called Aducanumab. Currently, this is only available in the US. You can find out more about this milestone for dementia research here.

Aducanumab is the first drug to tackle the underlying disease processes in Alzheimer’s. We can’t find the best treatment for the diseases that cause dementia without finding the first. We hope that this announcement will open the door to a generation of new and better treatments in the future.

At Alzheimer’s Research UK, we are committed to finding new treatments that slow or stop the diseases that cause dementia.

We won’t stop until we find them.

 

What is our Drug Discovery Alliance?

Our Drug Discovery Alliance is one of the ways that we are speeding up the search for new dementia treatments. The Alliance unites three cutting-edge institutes based at the University of Oxford, the University of Cambridge, and University College London (UCL).

Our Drug Discovery Alliance bridges the gap between new knowledge about the causes of dementia and the discovery of new treatments.

They test new approaches for dementia treatments, previously unexplored by the pharmaceutical industry. This means searching far and wide for the best ideas from the research community.

John Skidmore is the Chief Scientific Officer of our ALBORADA Drug Discovery Institute in Cambridge.


How does the drug discovery process work?

  1. Discover

There’s so much high-quality, creative science taking place in universities, increasing our knowledge of what goes wrong in the diseases that cause dementia.

How does increasing our understanding of the diseases that cause dementia lead to new treatments? It certainly doesn’t happen by itself!

As scientists at universities make sense of how our brains work and how they can be damaged by diseases, our Drug Discovery Institutes identify the most promising ideas to test.

Our Drug Discovery Alliance has formed over 135 collaborations across the world to translate ground-breaking discoveries about the causes of dementia into potential treatments that can be taken into clinical trials.

  1. Develop

The teams of biologists and chemists at the Drug Discovery Alliance harness promising new ideas from universities and bring these into the drug discovery pipeline.

The Chief Scientific Officers at our Drug Discovery Alliance have the challenging role of choosing the most promising targets to focus on. A target is a protein or pathway that plays a role in the course of the disease that we can modify with drugs to help stop damage in the brain.

The biologists study exciting new targets in depth to confirm the role they play in diseases like Alzheimer’s. These rigorous checks ensure that a specific target leads to nerve cell damage, rather than being an innocent bystander.

It’s the chemists’ job to find the best chemical compound. Chemists have to make thousands of subtly different chemical compounds to find the perfect match. Not only must the compound bind to the target and change the way it works, there are loads of other things to consider! Including, importantly, if it’s safe.

Once they’ve found the best compound, the impact of the potential new drug has to be tested in human cells and mice before it can enter clinical trials. The team look for signs of side-effects and more evidence that the compounds will be effective against the disease.

  1. Optimise and trial

The Drug Discovery Alliance focuses on the early stages of drug development, finding the best chemical compounds.

Industry partners have the expertise and resource to take on promising projects once they emerge from this process. They further optimise the potential new drug and take it on towards clinical trials.

Our Drug Discovery Alliance has already partnered in over 35 research projects with pharmaceutical and biotech companies.

Ultimately, industry partners have the resources to support expensive trials that will get potential drugs out of the lab and into the hands of the people who need them, but they are less likely to support the riskier early stages of drug discovery.

Our Drug Discovery Alliance is bridging that gap.

drug discovery phases

 

Why explore multiple new treatment approaches?

The early stages of drug discovery are the most risky, with few potential new drugs making it into clinical trials, and even fewer getting regulatory approval.

It takes over 10,000 chemical compounds to get the right one!

This means to have the best chance of success in developing new life-changing treatments for dementia, we have to explore as many potential avenues as possible.

It’s essential to explore new approaches to tackle the different processes that go wrong in the diseases that cause dementia. Like in cancer, a combination of multiple drugs that tackle different harmful processes in the disease are likely to be most effective at slowing or stopping disease progression.

Our Drug Discovery Alliance maintains a strong pipeline of new ideas going through these early stages of drug discovery. The Alliance has already worked on over 60 different targets.

 

What are exciting projects happening at the moment?

Our Drug Discovery Alliance is working on over 20 potential new treatments for dementia right now.

Here are three exciting new areas the Drug Discovery Alliance is exploring!

Targeting inflammation

Microglia are immune cells that usually clear up waste to maintain a healthy brain environment.

In Alzheimer’s, microglia can drive damage to nerve cells by promoting inflammation, while not clearing the threat posed by the build-up of toxic proteins.

Our Drug Discovery Alliance has found three promising targets that have the potential to slow or stop disease progression and have already identified chemical compounds that hold promise as the basis of potential new drugs.

A supporting role

Astrocytes are the most numerous cell type in the brain. These beautiful star-shaped cells are crucial support cells that have a number of important roles, including providing nerve cells with chemicals that are vital for their normal function.

In Alzheimer’s disease, astrocytes go wrong and start causing damage.

Our Drug Discovery Alliance has identified a potential way to control the activity of astrocytes and allow nerve cells in the brain to function better for longer.

AstronautX is a biotech company that was formed based on these findings from the Drug Discovery Alliance. Together, they are going to move this project as quickly as possible to clinical trials.

Maintaining a balance

Proteins are the building blocks of life. There are an enormous variety of proteins in our bodies, and the activity of these complex molecules is what drives the processes that keep our cells functioning.

Proteins are in constant flux in our cells. They are made, folded into the correct shape, kept in check and recycled by the cells’ waste disposal machinery.

A key hallmark of many of the diseases that cause dementia is the build-up of abnormally-folded proteins.

Our Drug Discovery Alliance is investigating mechanisms for removing unwanted proteins, to stop them damaging cells and ultimately keeping brain cells healthier for longer.

Currently there are two projects in the final stages of the drug discovery process close to being taken on for further development by industrial partners.

 

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About the author

Claire Bromley