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Is Alzheimer’s drug discovery targeting the impossible?

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Written by Simon Beaulah, SVP of Healthcare, PrecisionLife Connect with Simon here

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Reversing the trend in Alzheimer’s disease drug discovery

Clinical trials in Alzheimer’s disease have had a 99% failure rate. It is time for a new approach. Unique combinatorial analytics has identified multiple clear subgroups with druggable biological mechanisms within Alzheimer’s disease patient population, making effective personalized treatments a real possibility for the first time.

The first thing that comes to my mind when I think of Alzheimer’s disease is a cup of tea.

My grandmother suffered from Alzheimer’s disease. It wasn’t obvious before her husband passed away, you notice occasional memory lapses but her day-to-day routine hid the effects. Once she moved into a care home, her short-term memory issues were much plainer to see.

She was always a wonderful host and keen to make sure I had a cup of tea during a visit. If I didn’t want one, she would ask, “Cup of tea?” again after a few minutes. And again, and again.

It’s tragic seeing someone you love slipping away in this way and this is hardly the most severe aspect of Alzheimer’s.

I wish like so many others that there were effective treatments and a way to screen for susceptibility to Alzheimer’s. Most of all I wish we could take action.

Alzheimer’s presents and progresses in different ways – with 6 million people a year being diagnosed in the US alone and over 50 million people are believed to be living with Alzheimer’s disease worldwide, you probably know someone who has been affected as well.

Everyone is frustrated by the 200 clinical trials that have been run with only limited success. However, there has been much excitement with the approval of Biogen’s new drug, Aduhelm, even though there have been issues and some push back.

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PrecisionLife analysis of 882 Alzheimer’s disease patients – Colors represent patient subgroups, circles represent disease associated SNPs and edges represent co-associated SNPs

High resolution patient stratification creates opportunities for the development of new treatments

Our work at PrecisionLife focuses on understanding complex, chronic diseases like Alzheimer’s and how clinical, environmental and genetic factors act together to create the disease state. It is acknowledged that chronic disease is often a heterogenous set of conditions that have different causes and are grouped together based on the symptoms and phenotype they present.

Our approach looks at combinations of factors across thousands of patients and millions of data points, something conventional AI and statistical approaches are not able to cope with, without losing signal.

Our initial combinatorial analytics work into Alzheimer’s is showing a remarkable subgrouping of people with specific biological processes underlying their diagnosis.

In our analysis of the UK Biobank data, PrecisionLife’s unique combinatorial analytics identified six clear subgroups, each with a distinct druggable biological mechanism.

This high resolution patient stratification highlights how if a drug targets the biological mechanism of one sixth of the clinical trial population it will not show enough effect. No wonder there are such issues with clinical trial efficacy.

If used at diagnosis these insights could inform treatment selection and give guidance into disease trajectory. Novel drug targets could be identified for specific sub-populations. Selective biomarkers could help identify the right people for clinical trials who have a consistent biological driver and are far more likely to respond to the targeted treatment.

There are many possibilities, but they all take a lot of effort.

Having spent over 25 years in genomics and clinical research focused on improving use of data I know that achieving a deeper understanding of complex disease takes an army of people collaborating.

Building new patient data sets, sequencing the samples/specimens, integrating, managing and analyzing huge data sets takes huge resources.

At PrecisionLife, we make the data do the hard work for us. We are applying a new and unique approach to drug discovery that enables greater precision, greater efficiency and greater outcomes.

Time to change the course of Alzheimer’s R&D

If you are active in the Alzheimer’s discovery and development space, we can improve your likelihood of success.

PrecisionLife is striving to deliver options for unmet medical needs. We are committed to finding better precision medicine treatment options for Alzheimer’s disease and similar chronic diseases that affect so many lives.

We must all work together to improve our understanding of complex disease. With new momentum and insight, now is the time to bring precision medicine to Alzheimer’s disease.

PrecisionLife is seeking partners in Alzheimer’s drug discovery and clinical development interested in collaborating to bring novel medicines to market, driven by precision medicine.

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Ask us a question or contact us to discuss potential collaborations and partnership opportunities by sending us a message here and we'll get back to you as soon as we can.

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