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>Autoimmune Polyglandular Syndrome type 1 (<a href="https://rarediseases.org/rare-diseases/autoimmune-polyglandular-syndrome-type-1/">APS-1</a>), also known as Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED), is a rare autosomal recessive condition which leads to devastating disease in children. APS-1 is caused by mutations in the autoimmune regulator gene (AIRE) which plays a key role in central tolerance mechanisms. Deficiency of AIRE function in medullary thymic epithelial cells (mTECs) results in the immune system launching an attack on numerous tissues and organs including the pancreas, intestine, stomach, thyroid, liver and skin. The clinical spectrum of APS-1 includes more than 20 different organ-specific autoimmune disorders and patients often present a combination of several manifestations at the same time. </p>
<p>The prevalence of APS-1 is estimated at 1:100,000 (<a href="https://pubmed.ncbi.nlm.nih.gov/28819917/">Kahaly and Frommer, 2018</a>). A high prevalence found among some geographical areas in certain populations including the Iranian Jews (1:9000), Sardinians (1:14,400), Finns (1:25,000), Norwegians (1:80,000) , and Irish (1:130,000).</p>
<h1 id="technology-overview">Technology Overview</h1>
<p>Researchers at The University of Sheffield have recently developed a gene therapy vector with the ability to mediate non-specific AIRE replacement <em>in vivo</em> and bring about a reduction of APS-1-related symptoms in C57/B6 AIRE-mutant mice when delivered via intrathymic injection (<a href="https://pubmed.ncbi.nlm.nih.gov/32994995/">Almaghrabi et al 2020</a>). They now plan to create and develop a patentable gene therapy vector with the ability to selectively restore AIRE function in mTECs and treat APS-1 patients via the IV route of administration.</p>
<h1 id="benefits">Benefits</h1>
<p>Treatment options for APS-1 are currently limited to symptomatic therapies and are complicated due to the multi-organ involvement. Treatments include hormone replacement therapy for endocrine disorders, antimicrobials for candidiasis, or immunosuppression for hepatitis and malabsorption. These have some serious adverse effects, for example immunosuppressive drugs may increase the occurrence of infection, sepsis and cancer.</p>
<h1 id="applications">Applications</h1>
<ul>
<li>Treatment of APS‑1</li>
</ul>
<h1 id="opportunity">Opportunity</h1>
<p>Seeking a development partner to help develop and optimise AIRE gene therapy for humans. In the first instance, funding for a technician for two years would significantly accelerate development towards the clinic.</p>
