How Big Data and collaboration are redefining a rare form of dementia
February 10, 2020
Van Andel Institute’s Dr. Rita Guerreiro and Dr. José Brás have teamed up with more than 100 other scientists from around the world to take on frontotemporal dementia, a rare disease that currently has no cure and no treatment that slows progression. In late 2019, the group led by Dr. Jonathan Rohrer at University College London published a wide-ranging study in The Lancet Neurology that provides new insight into FTD that could one day shape future treatments.
Here’s a quick primer on FTD and breakdown of their findings.
Frontotemporal dementia is rare and tough to define — and that makes it hard to study
For more than a century, the exact name and definition of frontotemporal dementia has been in flux. It is best described as a syndrome — a set of symptoms that often occur together. While the exact parameters of what constitutes FTD will likely evolve as we learn more, typical features of the disease include progressive shrinking of the frontal and anterior temporal lobes of the brain; that is, the brain’s front and bottom regions.
Other FTD symptoms fall into two categories:
- Behavioral changes, such as impulsive or listless behavior, inappropriate social behaviors, repetitive or compulsive behaviors, and agitation. (More information is available here)
- Difficulties with language, such as problems comprehending speech or with speaking. Often, these symptoms occur alongside behavioral symptoms.
About one-third of FTD cases are genetic, meaning the disease can be directly linked to changes, or mutations, in specific genes.
When it comes to rare diseases, collaboration is critical
Rare diseases like FTD can be tough to study due in large part to their nature. There often simply aren’t enough cases from which to gather sufficient data. Moreover, while FTD is a rare disease, FTD caused by DNA mutations is even rarer.
To establish what is typical for each mutation or for each gene, scientists must have enough cases with the same mutation or mutations in the same gene. This is only achievable by leveraging the collective power of research centers around the world. Each of these centers may only have a handful of cases but, when analyzed all together, scientists can start seeing patterns that would have been impossible to identify in the individual cohorts from each center.
In this study, the team was able to compare data from 3,403 individuals representing 1,492 families — far more than would be accessible at any one center. The result is a powerful overview of genetic mutations that contribute to age of symptom onset, age of death and length of disease in people with FTD.
The findings lay an important foundation for future research and future treatment
The study focused on the three genes most frequently mutated in FTD: MAPT, GRN and C9orf72. Here are a few examples from their findings:
- GRN mutations were more likely to affect women than men.
- People with MAPT mutations tended to be younger at symptom onset and at death.
- People with C9orf72 mutations had the shortest disease duration, on average.
Overall, the team was able to better characterize what is typical for rare mutations. This information is particularly important for people and families living with these mutations, for clinicians managing FTD and for drug developers assessing progression of disease in clinical trials.
Additionally, a large-scale, Big Data study such as this allows scientists to better define disease subtypes by country and, ultimately, can move the field one step closer to precision medicine.