Beyond the Ice Bucket Challenge: an interview with ALS expert Professor Ammar Al-Chalabi, Part Two

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In honour of ALS/MND Global Day on June 21, Best Doctors is pleased to feature Part Two of an interview with Prof. Ammar Al-Chalabi, a leading ALS specialist at King’s College London and director of STRENGTH, the world’s largest international consortium for studying the disease.

Part Two

Professor of Neurology and Complex Disease Genetics at King’s College London, Director of King’s MND Care and Research Centre and Honorary Consultant Neurologist at King’s College Hospital, Prof Al- Chalabi is a recognised specialist in ALS (amyotrophic lateral sclerosis, also known as motor neuron disease) whose work involves both clinical practice and research.

a photo of Prof. Ammar-Al Chalabi

You are the director of STRENGTH, the largest international consortium for studying ALS in the world. What is special about STRENGTH in terms of its focus and goals?

STRENGTH brings together researchers and clinicians from ALS centres across Europe to combine forces, with a focus on collecting and sharing anonymised clinical and biological information. The aim is to look at several risk factors at the same time in very large numbers of people to see why ALS happens. For example, we have a system to take all the information from ALS registers across Europe and to use that to find clinical patterns of ALS that are not obvious to humans, but can be identified by computer programs. We can then look at the genetic and environmental risk factors in each of these “hidden” types of ALS. We are in the process of doing this in the collective information of about 15,000 people with ALS. We have already been able to show the different ALS types lead to very different survival patterns. We have also used a similar technique to show that on average, six different disease-causing steps need to occur before someone will develop ALS.

According to the STRENGTH website, one of the obstacles to advancing in treatment for ALS is that “the design of new drugs is hampered by our lack of knowledge, and the tendency to consider all ALS as if it is a single, uniform disease”. Can you elaborate on this?

For years there have been debates between so-called “lumpers” who think that all the different patterns of ALS represent a single disease, and “splitters” who think that ALS is actually a collection of different conditions that look and behave similarly. This is an important distinction because it affects how we test if a new treatment is effective. For example, if there are really two different types of ALS and they respond differently to treatment, then our clinical trials will be negative. This is because the size of a trial is carefully calculated to make sure it is large enough that it could detect a treatment effect. A hidden subgroup would dilute the numbers that could actually respond to treatment and reduce the apparent trial size. STRENGTH can show how much we should lump or split ALS, which should improve our clinical trials.

Last year’s “Ice Bucket Challenge” was nothing short of a social media sensation, with celebrities and world leaders dousing themselves for the cause.Now that the buzz has died down, what real results have emerged from the efforts?

There are many important outcomes from the Ice Bucket Challenge. At the simplest level, it has greatly raised awareness of ALS in the general population, which is very important for research funding and participation. It has also meant that flagship projects could be accelerated. For example, with funding from the MND Association, we are working within STRENGTH and an international consortium called Project MinE, to analyse the entire genomes of 15,000 people with ALS and compare them with the genomes of 7,500 unaffected people. By understanding the differences between the two groups we can understand the pathways that lead to ALS. This is a true “big data” project – each of the 22,500 sequences fills a hard drive. Although the first human genome to be sequenced took 16 years and cost hundreds of millions of pounds, each genome now costs about £1000. The Ice Bucket Challenge has allowed us to do this important study more quickly. Another result of the Challenge is that the ALS charities have been able to work with researchers to plan large-scale strategies to tackle ALS. This is particularly true for the ALS Association in the USA, but also for the MND Association in the UK.

From a medical or research point of view, were there any negative consequences to the Ice Bucket Challenge?

There are two that come to mind. First, there was increased scrutiny of the ALS charities, some of which was inappropriately negative and did not recognise the dedication and effectiveness of the people involved. Second, as researchers, our work relies on a continuous and reliable stream of funding – we need a continuous ice bucket. Our experience with other diseases shows that sufficient funding is a very effective tool for developing an effective treatment. For example, many cancers are now curable or very treatable, and HIV infection can now be very successfully treated where it was originally a death sentence.

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