People with Alzheimer’s disease (AD) have a build-up of tau proteins in the brain which stick together and become tangled. These ‘tangles’ damage the internal structure of nerve cells affecting how they work and eventually causing them to die. This leads to brain tissue damage and a decline in memory and thinking.

Dr Ross Paterson is leading the NIO-SILK study at UCLH, which is sponsored by UCL. He is a Principal Research Fellow at UCL Queen Square Institute of Neurology and consultant neurologist at the UCLH National Hospital for Neurology and Neurosurgery, Queen Square, London. Participants at UCLH will have the study medication and study tests at the NIHR UCLH Clinical Research Facility at Queen Square, with the study supported by the NIHR UCLH Biomedical Research Centre.

Research for new treatments in AD have largely focused on a protein called amyloid in the brain and anti-amyloid therapies have been trialled over the past two decades. While the first clinical trials of amyloid therapies show modest impact on clinical disease progression, their ability to transform or halt disease progression remains unknown. Targeting the tau proteins in the brain may provide more clinical benefits. This initial early phase trial is testing the effect of NIO752 on the rate of tau production, how safe it is and how the body reacts to it. 

The tau protein is made from a gene called MAPT. NIO75 is an antisense oligonucleotide (ASO). Antisense technology is a way of disrupting how proteins are made. NIO752 targets the MAPT gene product and reduces the amount of tau protein that is made in the brain. It is hoped that this could slow the progress of Alzheimer’s disease.

The main aim of this trial is to assess how much NIO752 reduces the rate of tau production in people with mild to moderate Alzheimer’s disease. To do this tau levels will be measured in the spinal fluid (cerebrospinal fluid or CSF). Any tau protein produced will be labelled or marked with a special type of essential amino acid (the building blocks of proteins) called leucine. This is a harmless food supplement given intravenously via a tube that will be placed into the participants vein. This process of labelling the tau is known as SILK (short for stable isotope labelling kinetics) and is expected to be a more sensitive way of capturing tau proteins compared to simply measuring the levels in the CSF.

Ten people with mild to moderate Alzheimer’s disease are being invited to join this trial.  In addition to UCLH, Washington University St Louis in the USA is supporting the trial. 

The trial is a ‘randomised trial’. Six out of 10 participants will receive the active drug NIO752 and 4 out of 10 will receive placebo treatment.

The trial is co-ordinated through the Dementia Translational Research Collaboration Trials Network, which is hosted at UCLH and led by Prof Cath Mummery, a UCLH consultant neurologist and Head of Clinical Trials at the Dementia Research Centre, UCL Queen Square Institute of Neurology.

Dr Paterson said: “We are proud to recruit the first participant in this global trial. This research is at an early stage, but we believe there is promise in targeting tau in the brain and we hope to be able to accurately measure how much tau production is impacted."

Professor Catherine Mummery said: “The aim of our dementia trials network hosted at UCLH is to develop early phase trials of innovative new drugs for dementia and Alzheimer’s disease, and this trial is an example of the type of trial we want to push forward. We are at an exciting time in dementia research and while we are making progress in therapies targeting amyloid, it is vital we take a multi-pronged approach and also explore treatments such as those looking at tau.”

University College London (UCL) are the sponsor of the trial.  The Joint Research Office (JRO) at UCL and UCLH provided the specialist knowledge and expertise to enable this study to be set up.  The JRO is supported by the NIHR UCLH Biomedical Research Centre.

The study is funded by the Alzheimer’s Association and the Sigrid Rausing Trust (UCL Neurogenetic Therapies Programme).

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