Professor Dr John C. van Swieten
Director, Alzheimer Centre Erasmus Medical Centre, Rotterdam
Frontotemporal dementia is an early-onset disease striking patients in their 50s and 60s with devastating outcomes.
Frontotemporal dementia (FTD) is a rare hereditary disease which progresses rapidly in patients. There is no recognised treatment for FTD, though a number of clinical trials for therapies are showing promise.
Neurologist John van Swieten, who is Professor in the Genetics of Dementia and Director of the Alzheimer’s Centre at the Erasmus Medical Centre in Rotterdam, has been working on the condition – also known as Pick’s disease – for almost 30 years.
Genetic mutations
The first mutations of the tau gene were identified in the late 1990s, before mutations in the progranulin gene were discovered in 2006.
He has produced several papers on the neuropathology of the disease after FTD patients donated their brains to the Dutch Brain Bank for research.
FTD is caused by a mutation in one of three genes – GRN, C9orf72, and MAPT – which trigger different behaviours and symptoms.
Professor van Swieten explains that with MAPt (tau) patients become often disinhibited with extreme restlessness and roaming behaviour; patients with progranulin (pGRN) manifest more with language problems; and those with C9orf72 mutations, the symptoms are forgetfulness, language issues and psychotic symptoms.
Early onset dementia
He says: “The classical symptoms of frontotemporal dementia are severe behavioural changes. Later, the clinical phenotype extends to patients resembling Alzheimer’s disease with forgetfulness, to those with purely language problems, and even with Parkinsonian signs. Even the symptoms vary considerably within a family.
“It is early onset dementia with 80% of cases developing in people aged 50-65. They progressively deteriorate in five to seven years, so it is completely different from Alzheimer’s where that might be much longer.”
In families where the disease occurs, FTD may be recognised early, but in other families it often takes much longer to realise something is seriously wrong.
“It might be aggression at work or relationship problems. In patients with C9orf72 mutation and psychotic symptoms, FTD can be difficult to recognise in the early stage because there are so many other causes for that kind of behaviour,” he adds.
Genetic testing can be of value to concerned relatives who may want to find out if they have the mutation and avoid passing it on.
Promising trials
While treatment options are limited, Professor van Swieten says promising trials are targeting genes.
With pGRN, therapies are looking to restore levels of the protein in FTD patients, while with C9orf72 the focus is on genetic engineering.
Professor van Swieten’s team in Rotterdam has been following 200 healthy family members who are genetically at risk of FTD since 2010.
“We have seen changes in specific proteins in blood, but also changes on MRI one FTor two years before presentation of clinical symptoms” he says.
“That is important as the time window to treat patients is relatively short because after one or two years, they become too demented.”
In the Dutch research, and in European GENFI cohort co-ordinated from London, researchers have seen participants developing FTD.
