Title: NIHR Sheffield BRC
Funder: Department of Health and Social Care

Abstract: Translational Neuroscience is the discovery pathway that develops basic findings, related to neurological diseases, into new effective treatments. This pathway extends from research into underlying disease mechanisms, through the process of identifying key molecular changes leading to disease (target identification) and screening for drugs that correct the problem (lead compound identification), to testing of promising compounds in clinical trials. A parallel translational research stream, acknowledging that many of these brain diseases do not yet have treatments that change the underlying disease processes, involves the development and testing of symptomatic treatments that improve patient experience and quality of life. Sheffield Teaching Hospitals (STH) is one of the largest hospital Trusts in the UK. It has a very large component of Clinical Neurosciences serving a population of 2.4m people in South Yorkshire and surrounding regions. STH has developed its capability to undertake clinical research through the creation of Academic Directorates that focus and prioritise clinical research with access to dedicated funds. Neuroscience was the first of these directorates to be established and is the most effective and successful. The hospital also runs a successful Clinical Research Facility, the place where clinical research studies and trials are carried out, supported by hospital staff trained to the highest research standards. Thus, the hospital is very well placed to deliver the clinical end of the translational discovery pathway, and has large cohorts of patients with the major neurological diseases that are the focus of the proposed BRC (dementia, motor neuron disease, Parkinson s disease, multiple sclerosis, and stroke). The University of Sheffield (UoS) has recognized its strength in Translational Neuroscience and is supporting this with major investments. One of these was the creation of the Sheffield Institute for Translational Neuroscience (SITraN). Evidence of the quality of this environment and its researchers includes their contribution to the UoS submission in Biomedical Sciences to the UK research quality assessment exercise (REF2014) where it was ranked 1st. SITraN is designed to take research in the translational pathway through to the development of lead compounds for human safety and efficacy testing. Thus between SITraN and the NHS research environment in South Yorkshire there is a gap in the pathway at present which the proposed BRC will fill. The BRC will harness the research output of SITraN to patient populations so that early clinical studies, and early clinical trials of medicines, can be tested. The proposed BRC includes other areas of UoS research strength to enhance its effectiveness. These include: expertise in analyzing genetic information using modern advanced techniques; new ways that disease progression, and the effectiveness of treatments, can be assessed by modern neuro-imaging methods; and a group specializing in approaches to personalize medicine so that each individual has access to the treatments that are best suited to their disease. A Sheffield BRC will strengthen and complement the NIHR portfolio of BRCs and BRUs, bringing access to cutting edge translational research and increased availability of clinical studies and trials to the people of the region suffering from chronic neurological conditions.

Lay abstract: Translational Neuroscience is the discovery pathway that develops basic findings, related to neurological diseases, into new effective treatments. This pathway extends from research into underlying disease mechanisms, through the process of identifying key molecular changes leading to disease (target identification) and screening for drugs that correct the problem (lead compound identification), to testing of promising compounds in clinical trials. A parallel translational research stream, acknowledging that many of these brain diseases do not yet have treatments that change the underlying disease processes, involves the development and testing of symptomatic treatments that improve patient experience and quality of life. Sheffield Teaching Hospitals (STH) is one of the largest hospital Trusts in the UK. It has a very large component of Clinical Neurosciences serving a population of 2.4m people in South Yorkshire and surrounding regions. STH has developed its capability to undertake clinical research through the creation of Academic Directorates that focus and prioritise clinical research with access to dedicated funds. Neuroscience was the first of these directorates to be established and is the most effective and successful. The hospital also runs a successful Clinical Research Facility, the place where clinical research studies and trials are carried out, supported by hospital staff trained to the highest research standards. Thus, the hospital is very well placed to deliver the clinical end of the translational discovery pathway, and has large cohorts of patients with the major neurological diseases that are the focus of the proposed BRC (dementia, motor neuron disease, Parkinson s disease, multiple sclerosis, and stroke). The University of Sheffield (UoS) has recognized its strength in Translational Neuroscience and is supporting this with major investments. One of these was the creation of the Sheffield Institute for Translational Neuroscience (SITraN). Evidence of the quality of this environment and its researchers includes their contribution to the UoS submission in Biomedical Sciences to the UK research quality assessment exercise (REF2014) where it was ranked 1st. SITraN is designed to take research in the translational pathway through to the development of lead compounds for human safety and efficacy testing. Thus between SITraN and the NHS research environment in South Yorkshire there is a gap in the pathway at present which the proposed BRC will fill. The BRC will harness the research output of SITraN to patient populations so that early clinical studies, and early clinical trials of medicines, can be tested. The proposed BRC includes other areas of UoS research strength to enhance its effectiveness. These include: expertise in analyzing genetic information using modern advanced techniques; new ways that disease progression, and the effectiveness of treatments, can be assessed by modern neuro-imaging methods; and a group specializing in approaches to personalize medicine so that each individual has access to the treatments that are best suited to their disease. A Sheffield BRC will strengthen and complement the NIHR portfolio of BRCs and BRUs, bringing access to cutting edge translational research and increased availability of clinical studies and trials to the people of the region suffering from chronic neurological conditions.

Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: NEUROLOGICAL;STROKE