The University of Sheffield

<p><strong>Overview:</strong></p>
<p>The University of Sheffield is a world top-100 university renowned for the excellence, impact and distinctiveness of its research-led learning and teaching. The University’s outstanding performance for excellent teaching and research, as part of a genuinely global community, is consistently confirmed by international independent assessments.</p>
<p>The university takes its public and social responsibility seriously. It is committed to making the world a better place. This approach is embedded in everything they do, from partnerships with local and global organisations to their research and teaching.</p>
<p><strong>Research:</strong></p>
<p>The University of Sheffield has a global reputation for world-leading research that makes a difference. It influences policy, changes lives and helps in understanding the world so that we can make it better. The university has over 180 research institutes, centres and groups. They address challenges from finding a cure for motor neurone disease to building a sustainable economic recovery. The research institutes and centres at the university have been created to address global challenges facing society, today and in the future. They are often interdisciplinary, with external collaboration and funding, and have earned international recognition.</p>
<p>The world-class research being undertaken at the University of Sheffield generates a wealth of new knowledge, much of which has the potential for licensing to innovative organisations seeking to augment their current activities or diversify their operations.</p>
<p><strong>Industry Partnerships:</strong></p>
<p>The University of Sheffield is collaborating with partners in the private, public and third sectors to find real-world solutions to real-world problems.</p>
<p>The university partners with organisations large and small, believing that by working together, we can find novel solutions to real-world problems. In their experience, it leads to world-class research and commercial success to businesses around the world. Together, The University of Sheffield shares knowledge, facilities and industry insight to help influence cultural, social, economic and political change.</p>


<h1 id="background">Background</h1>
<p>Motor neuron disease (MND) is a devastating and rapidly-progressive orphan disease which leads to paralysis and death usually within five years from diagnosis. There are currently no therapies which slow or stop the accumulation of debilitating symptoms resulting from the underlying neurodegeneration. In the UK at any one time around 5,000 people are living with MND; 55,000 people have MND across France, Spain, Italy, the UK, USA, Japan and Germany. There are around three new cases of MND per 100,000 people, per year. </p>
<p>Frontotemporal dementia (FTD) is the second most-common form of early-onset dementia. It manifests as profound personality abnormalities and is debilitating for sufferers and their families. There are approximately four new cases per 100,000 people, per year. </p>
<p>These two diseases have in common mutations in a gene called C9ORF72. &gt; 10% cases of MND/FTD have C9orf72 expansion mutations. C9orf72 expansions are bidirectionally transcribed leading to the formation of intracellular sense and antisense RNA repeat expansion (RRE) foci. Moreover, the transcripts are prone to repeat-associated non-ATG (RAN) translation producing dipeptide repeat proteins (DPRs). </p>
<p>RuvBL1/2 are proteins with a cellular role in clearing aggregated proteins and manipulating DNA. They interact with the protein product of a gene called MATR3 which is associated with MND. Because of the MATR3 connection and because it is known that DNA damage and protein aggregates are a feature of MND, the researcher team wanted to see if RuvBL1/2 levels are changed in cells from patients with MND and if manipulation of RuvBL1/2 levels could ameliorate the disease phenotype.</p>
<h1 id="technology-overview">Technology Overview</h1>
<p>Researchers have shown that overexpression of RuvBL1/2 decreases DNA damage markers and the expression of C9ORF72‑related DPRs. They have generated AAV vector constructs that express RuvBL1 or RuvBL2 and are currently planning to test these in mice with C9ORF72 mutations.</p>
<h1 id="benefits">Benefits</h1>
<p>The only approved treatment for MND in Europe and the US is riluzole but it offers at best a small increase in survival time for patients. There is a gap for a significantly better disease‑modifying treatment for MND. AAV RuvBL1/2 gene therapy promises to provide disease modification from a single dose.</p>
<h1 id="applications">Applications</h1>
<p>The gene therapy vectors encoding RuvBL1/2 could be used as a treatment for the 10% of MND patients and FTD patients that have the C9ORF72 mutation. Furthermore, increased activity of RuvBL1/2 could also treat more‑common protein aggregation diseases including Alzheimer’s disease and Parkinson’s disease.</p>
<h1 id="opportunity">Opportunity</h1>
<ul>
<li>Looking for investors, collaborative development partners and funders to help us continue the RuvBL1/2 gene therapy programme.</li>
</ul>
