FTD researchers have recently returned from Vancouver where they attended the biennial international FTD conference. The meeting has slowly grown over the years with increasing interest in the FTD field, and nearly 600 people attended the conference from around 30 countries and a wide variety of research was presented from new brain imaging markers through to novel drugs.
Your FTD talk team were there and live tweeted the meeting (see our @FTDtalk account on Twitter) but here is a selection of highlights of the meeting:
Tau PET imaging
Brad Dickerson from Harvard and Makoto Higuchi from Chiba described two new ways of trying to identify the tau protein by using a type of brain imaging called a PET scan. Dickerson used a marker called AV1451 or T807 and showed changes in the brain in people with mutations in the tau gene even before symptom onset, although he did also show changes in semantic dementia, which is more commonly a disease associated with the TDP-43 protein. Higuchi has been researching a different marker called PBB3 and showed changes in disorders commonly associated with the tau protein such as progressive supranuclear palsy as well as people with mutations in the tau gene. This is an exciting new type of imaging and we are waiting to hear more about this over the next year.
Large collaborative clinical studies
Work from the Genetic FTD Initiative (GENFI) was presented showing early brain imaging changes occurring before symptom onset, with a different pattern in the three main genetic FTD subtypes (tau, progranulin and C9ORF72). GENFI is a multicentre study across Europe and Canada with 13 centres part of the initial GENFI1 but more centres are now joining this study for GENFI2 starting in 2015.
Multicentre collaborations are now starting to grow in the FTD field and two new studies in the US have now been funded. It is hoped that these studies will provide important data about when the right time is to treat people and how such treatments should be monitored.
Behavioural variant FTD ‘phenocopies’
Over the last ten years there have been a number of reports of people who come to FTD physician’s clinics who have developed similar behavioural symptoms to FTD but don’t seem to change very much over time. People with this syndrome have been called a number of things including ‘non-progressive’ or ‘slowly progressive’ FTD as well as the term used by researchers, FTD ‘phenocopies’. John Hodges from Sydney talked about a series of 18 people with this syndrome and showed that in fact 2 of these people had a mutation in the C9ORF72 gene. In a separate talk John van Swieten from Rotterdam talked about 2 people who had come to post mortem with this syndrome who did not show any evidence of neurodegeneration in the brain. These two studies are helpful in telling physicians to watch out for the possibility of a C9ORF72 gene mutation but that we need to carry on researching this group of people to find out what those who don’t have such a mutation actually have going on.
William Hu from Emory University has been working on spinal fluid markers for a number of years. He showed that if you look at the ratio of two measures of the tau protein in spinal fluid (the phosphotau to total tau ratio) this can help to differentiate people with FTD who have underlying tau pathology and those that have TDP-43 pathology. This has been a longstanding problem in the FTD field – how do we work out during life what the actual abnormal protein is in people’s brain cells? This study and a similar one from the Amsterdam FTD group are a first step towards solving this using spinal fluid measurements. Hu also showed some initial data on markers of neuroinflammation (an important area of interest in FTD previously discussed on FTD talk) showing very early changes in a protein called TPP1.
Another important talk came from Len Petrucelli at the Mayo who has shown that a particular protein which is thought to be toxic to brain cells in people with mutations in the C9ORF72 gene can be found in spinal fluid – these are called dipeptide repeat proteins.
Holger Patzke from Forum Pharmaceuticals showed that the HDAC inhibitor they had developed increases progranulin levels. A phase 2a trial of this drug in people with mutations in the progranulin gene will be starting at multiple sites across the US and Europe in 2015. Other interesting talks were on anti-tau antibodies and a potential drug called antisense oligonucleotides, but both of these were some time away from trials in patients.
Whilst we develop so-called ‘disease-modifying’ treatments, in other words drugs that might slow, stop or reverse the disease process, we should not forget that there are important treatments for people’s symptoms being developed. Elizabeth Finger from London Ontario talked about the use of inhaled oxytocin which has previously been suggested as a treatment for some of the behavioural symptoms of FTD – she is planning to move to a larger trial soon.
It was an exciting meeting and there was a sense of hope that the FTD field was moving forward quickly. The next meeting is in Munich in 2016 – hopefully by then we will have moved substantially forward in each of these highlighted areas.