The genetic data of almost one million Emiratis is to be used to help in trials of a therapy that could prevent Alzheimer’s disease.
The drug will be given to Emiratis without symptoms of Alzheimer’s, but whose genes have been identified by the Emirati Genome Programme as being at increased risk of developing the condition.
The trials involve M42, the Abu Dhabi healthcare company whose expertise includes genetic studies, the emirate's Department of Health and Halia Therapeutics, the US company behind the therapy.
The programme is an initiative to create a genetic map of as many UAE citizens as possible to advance preventive health care. It has currently gathered the DNA of more than 900,000 citizens and the Department of Health will send text messages to people thought to be eligible for the trials to undergo screening.
M42’s Insights Research Organisation and Solutions (IROS) division is to lead the trials. David Kavanagh, interim general manager of IROS, said the trial reflected “a decade of genomic investment" in the UAE. “The Emirati Genome Programme was built to improve health outcomes, and today we are translating that data into real-world clinical research,” he added.
Dr David Bearss, president and chief executive of Halia Therapeutics, said use of the programme and M42’s assistance in the project would enable “a prevention-focused clinical trial”.
“We are not waiting for disease to appear. We are acting at the moment when intervention can matter most, and the Emirati Genome Programme gives us a population-scale platform to do so,” he said. “That is why we have established a presence in Abu Dhabi, and we are excited to show the world what the future can look like when we use these tools to focus on early intervention in high-risk populations.”
About a quarter of people have a single copy of the APOE4 gene variant, having inherited it from one of their parents. Those individuals are at least twice as likely as the average person to develop the disease, while those with two copies of APOE4 make up about two per cent of the population and are even more likely to have the condition.
In recent years, the first treatments thought to slow the progression of Alzheimer’s have been released. Those drugs work by removing deposits in the brain of a protein called amyloid, but such deposits have not been proven to cause the disease and the benefits of the drugs appear to have been modest. That has led some health regulators to recommend against further funding.
The therapy to be tested in the coming trials is called HT-4253 and it works in a different way, inhibiting a gene called LRRK2. In doing so it is thought to prevent the inflammation of nerve cells and stop the build-up of the amyloid protein.
Rob Howard, professor of old-age psychiatry at University College London, told The National that the change in focus was “exciting”.
“This is welcomed, because it’s an alternative to the amyloid idea. It represents diversity in Alzheimer’s research,” he said. “Too much drug development has been focused on trying to remove or reduce amyloid. The drugs that remove amyloid don’t seem to make very much difference to dementia, although they clear out the amyloid … we really need to see a different class of drugs being tried.”
He added that it “makes sense” to provide therapies to people before they reach old age, because it could mean they have “hopefully many years of useful life ahead of them”. But he cautioned that there was no guarantee the drug would generate positive results.
“Until we see the data from the trials, we shouldn’t speculate,” Prof Howard said. “It’s possible they will do nothing at all. The field is littered with drugs that failed.”
Last year, Halia Therapeutics, which is based in Utah, announced it had completed early-stage clinical trials of HT-4253 in Australia. Prof Paul Morgan, a group leader at the Dementia Research Institute at Cardiff University, told The National that while APOE4 is a "useful indicator of increased risk” of developing Alzheimer’s, it is not definitive.
He added that it was valuable to develop ways to identify those at risk before symptoms developed, because “once dead, brain cells don’t come back”.
Dr Noura Al Ghaithi, undersecretary at the Department of Health, said in a statement that the genome programme showed that the UAE wanted to use data to create a "more precise, proactive and prevention-focused healthcare system”.
“By integrating genomic data into clinical research, in collaboration with our local and international partners, we are advancing a model of personalised health care that enables earlier risk detection, accelerates diagnosis and supports the development of more targeted and effective preventive and therapeutic interventions tailored to each individual’s genetic profile,” she added.
Until now, much genetic research has focused on western countries, so the UAE's programme provides much-needed information about a previously under-researched population.
The Middle East has one of the fastest-ageing populations in the world, owing to falling birth rates and people living longer. More than 57 million people around the world have dementia, a study found, with the number of people with dementia or Alzheimer's expected to reach 153 million by 2050. Alzheimer’s causes more than 60 per cent of dementia cases.
