Geneticists at QIMR Berghofer are excited about new developments in genetic and drug databases that could pave the way to repurpose existing drugs, accelerate clinical trials and allow patients access to other treatments.
Researchers from QIMR Berghofer and Vanderbilt University Medical Center have found several drugs that target the activity of genes linked to the common neurodegenerative condition.
The new study, published in the journal Neurology® Genetics, identifies a priority list of medications, already used for various conditions that could potentially be repurposed to alleviate the symptoms of Alzheimer’s disease.
The research is still in its early stages and the drugs will need to be further validated to test their efficacy against Alzheimer’s disease symptoms.
The head of QIMR Berghofer’s Translational Neurogenomics Laboratory and lead researcher Professor Eske Derks said the repurposing of existing drugs could accelerate clinical trials and allow patients to get access to new treatments sooner rather than later.
“The drugs we’ve identified are safe and have been approved to treat other conditions. If we can repurpose them to alleviate symptoms of Alzheimer’s disease, we can get new drugs to patients faster,” she said.
Juanita Hughes, an advocate for the needs of people with Alzheimer’s disease and dementia is impressed with the study.
“The study gave good evidence that this is actually a good way of repurposing drugs and by bringing more help to modify symptoms, it will allow people to live longer with a higher quality of life,” Juanita said.
Diagnosed with a familial form of dementia two years ago (not Alzheimer’s), Juanita grew up with family members who had dementia. She is now a member of Dementia Australia’s Advisory Committee, representing people living with dementia. Alzheimer’s disease is the most common form of dementia.
“I like the idea of repurposing medication because it’s a very expensive process to bring a new one online,” Juanita said.
It is not only her diagnosis that is driving Juanita’s advocacy, she also has a scientific background and is currently studying for a graduate certificate in diagnostic genomics.
“Medical research is vital. The more we know about a disease, the more we can do to prevent it,” she said.
Dementia Australia says current Alzheimer’s disease treatments improve quality of life for some people, but they don’t stop the progress of the neurodegenerative disorder.
Alzheimer’s is a complex disease. There is no one gene that causes it.
“Humans have around 50,000 genes. That’s the latest estimate. And there have been really large studies to look at which genes are responsible for causing Alzheimer’s,” Professor Derks said.
Previous research has identified 36 genes linked to the disease, and Professor Derks said their study developed a new analytical approach to link genetic data with large-scale drug databases.
“A lot of patients have contributed their DNA for genetic studies and now we want to bring it back to them and use that information to find new drugs,” she said.
Alzheimer’s disease runs in families. “The genes inherited at birth will influence the risk that the disease will develop later in life,” Professor Derks explained.
Genes that may be more active or more ‘highly expressive’ in patients with Alzheimer’s disease, may be the reason they have developed the disease. The potential drugs may reduce the activity of these genes and normalise them to what you’d expect to see in a healthy individual.
QIMR Berghofer researchers Dr Zachary Gerring and Associate Professor Anthony White contributed to the study, along with Dr Eric Gamazon at the Vanderbilt University Medical Center.
Associate Professor White grows microglia models in the lab at QIMR Berghofer. Microglia are immune cells found within the brain. His team adds the prioritised drugs to the microglia to test whether they change the activity of relevant genes.
While further research is needed, Professor Derks appreciates the importance of what has been achieved with genetic data recently and what is possible for translating this to the clinic and back to patients.
“We need better drugs. There’s just no effective treatment for Alzheimer’s disease and no effective drugs that will prevent it,” Professor Derks said.
Dr Gerring clarified, “So it’s about bringing in different bits of information. For every gene we know is associated with Alzheimer’s disease, we’re looking for a drug gene signature that opposes the disease signature. In other words, we are looking for an expression signature that normalises the disease signature.”
“If you normalize a disease signature, theoretically you can alleviate the symptoms,” Dr Gerring said.
With the theoretical side done, and the prediction that this compound will normalise the genetic changes of certain Alzheimer’s disease, the computational work needs to be validated in the lab.
“That’s why Associate Professor White’s work is so important, to observe experimentally what we’ve observed computationally using these large scale data,” Dr Gerring said.
Associate Professor Gamazon and Professor Derks are also leading an international research team that has received funding from the National Institute on Aging to continue their work to find more effective treatment for Alzheimer’s disease.
“This is research that wouldn’t have been possible until recently. The databases with genetic data of tens of thousands of Alzheimer’s disease patients, and these genetic studies, are all recent. The methods now available for this research, weren’t devised until 2016.” Professor Derks said.
“And it’s quite unique that at QIMR Berghofer, we have the combination of computational expertise and the opportunity to do the lab work as well.
It is really strong research to have this joint effort to tackle a disease,” she said.
Juanita also acknowledges tackling a disease, does require a joint effort.
“I take my hat off to anybody who donates to medical research. They are doing an invaluable service, because research doesn’t happen without funding and what they’re doing is making life better for people in my situation,” Juanita said.