Research into treating dementia before symptoms appear

Researchers are looking at ways of treating patients with an inherited type of dementia before symptoms develop.

In a new clinical trial at UCL, patients with a genetic form of frontotemporal dementia (FTD), the second most common form of young-onset dementia after Alzheimer’s disease, will receive an experimental drug called FRM-0334 intended to boost levels of progranulin in the central nervous system.

Due to a genetic mutation causing the failure of progranulin production, patients with this genetic form of FTD have abnormally low levels of progranulin.

Study lead Dr Cath Mummery, Associate Clinical Director in Neurology at the National Hospital for Neurology and Neurosurgery and Clinical Lead for cognitive disorders at the Dementia Research Centre, said: “Targeting therapies towards genetic abnormalities in patients that are not yet affected but known to be at risk is a big step forwards in clinical trials in dementia. In this case, the drug aims to normalise the abnormality caused by the genetic mutation by manipulating protein expression in the nervous system, a novel approach in clinical trials in dementia”.

Researchers first discovered in 2006 that mutations in the GRN gene can cause FTD. GRN-related FTD affects an estimated 3 to 15 per 100,000 people aged 45-64. This condition accounts for 5-10% of all FTD cases.

GRN-related FTD is rare, early-onset (symptoms usually become noticeable in a person's fifties or sixties) and inevitably progressive. It can affect behaviour, cognition, language and motor skills.

The condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has a parent and other family members with the condition. Currently there are no treatments to slow or stop the progression of the disease.

The GRN gene provides instructions for making progranulin which is active in many different tissues in the body, where it helps control the growth, division and survival of cells. Most mutations in the GRN gene prevent any progranulin from being produced from one copy of the gene in each cell, so cells make only half the usual amount of progranulin. Low levels of progranulin are associated with neuronal degeneration and raising the levels back towards normal is associated with a significant delay in symptom onset.

Graham Sankey’s wife Susan is one of the participants on the trial. This is the first time Susan will take a drug intended to alleviate the symptoms of GRN-related FTD. Graham said: “Susan being on the trial gives me hope that her condition may be stabilised. Even if it does not help Susan it may help others in the future”.

Professor Martin Rossor, Director of the NIHR Queen's Square Dementia Biomedical Research Unit and NIHR National Director for Dementia Research, said: “There has been a revolution in our understanding of degenerative dementias such as FTD. Since the genetic mutation causes a loss of function there is real optimism that this disease can be treated in the not too distant future”.

The trial is sponsored by FORUM Pharmaceuticals, a biopharmaceutical company focused on development of innovative medicines to treat brain diseases.