Queen's University

Overview
Founded in 1841, Queen’s University in Kingston, Ontario is one of Canada’s leading research-intensive institutions, combining quality and intensity in research with excellence in undergraduate and graduate education.
Research is a core component of the mission of Queen’s University. A member of the U15, a group of Canada’s leading research-intensive universities, Queen’s ranks highly in terms of research funding and research intensity amongst universities nationally.
Their commitment to research excellence is evident in the many exceptional national and international accolades awarded to their researchers, most recently Queen’s Professor Emeritus Dr. Arthur B. McDonald was awarded the 2015 Nobel Prize in Physics – with co-recipient Takaaki Kajita of Japan – in Stockholm, Sweden.
This excellence, found across disciplines – from health care, the environment, materials, energy, law, economics, culture, and many others – attracts the best students, the best faculty, and the best collaborators from local and global communities, other institutions, government, and industry.
Through their diverse programs, Queen’s university promotes social innovation, fosters creative expression, and explores how societies work best. And it’s this culture of excellence that has made Queen’s one of Canada’s leading research universities.
Queen’s Partnerships and Innovation
The Queen’s Partnerships and Innovation (QPI) team supports the advancement of partnerships, research collaborations, and knowledge mobilization as well as innovation, entrepreneurship, and economic development. The QPI team develops and facilitates partnerships with industry, governments, not-for-profit organizations, and other academic institutions to advance the research enterprise at Queen’s and the commercialization of inventions, and to strengthen the regional innovation ecosystem in Kingston and Eastern Ontario. 
With support from external funding, the QPI team offers numerous services, resources and programs to support entrepreneurs, including those from Queen’s, and to accelerate the growth of startups and small to medium-sized enterprises (SMEs) within Kingston and Eastern Ontario. The team has transformed more than 1,000 invention disclosures into hundreds of technologies covered by at least one patent; additionally, the team has supported the founding and-or acceleration of hundreds of startups and SMEs in the Kingston region.

<h1 id="background">Background</h1>
Rheumatoid arthritis (RA) is a disease characterized as a persistent synovial inflammation. RA has been found to affect 3.6% of women and 1.7% of men in the United States1. It costs approximately $13,500 USD each year to treat a single RA patient, resulting in a significant economic burden2.
Despite extensive research on this topic, the exact causes and mechanism of RA are not well understood. Inflammatory mediators result in elevated reactive oxygen species (ROS) in inflamed tissue. Both ROS and the inflammatory mediators have been found to trigger nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, leading to further production of pro-inflammatory cytokines. These cytokines induce the production of metalloproteinases, adhesion molecules, regulating immune cells, synoviocytes and chondrocytes, causing cartilage to degrade and ultimately resulting in joint space narrowing and joint destruction3.
Currently, non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve joint pain and swelling associated with RA. However, the adverse side-effects of these drugs towards the cardiovascular and gastrointestinal system limit their suitability as a long-term treatment for RA-induced chronic inflammation. Disease-modifying anti-rheumatic drugs (DMARDs) are the current gold standard with respect to controlling disease activity, but are also associated with many side effects including serious hepatotoxicity, bone marrow suppression, pulmonary complications and increased risk of infection4. Therefore, there is an urgent need for alternative anti-inflammatory methods which can effectively and efficiently treat RA-induced inflammation without exhibiting serious adverse effects.
Hyaluronic acid (HA) is a high molecular weight (&gt; 1 million daltons) glycosaminoglycan (GAG). Significant research now indicates that HA is more than an inert extracelullar GAG. A number of studies have found elevated levels of HA in serum and synovial fluid from patients with RA. However, further consideration of the molecular size of HA has now revealed the negative effects of endogenous low molecular weight HA in arthritic diseases (LMWHA; MW &lt; 500 kDa) including being pro-inflammatory. Indeed, LWMHA is not only increased in RA serum and synovial fluids but further increased in those fluids in active RA compared to inactive RA. LMWHA is produced by synthases (HAS1 and 3), by enzymatic cleavage, and by oxidative degradation. These negative effects are mediated by LMWHA binding proteins including toll-like receptor 4 (TLR4), CD44, RHAMM and others. For example, RHAMM is overexpressed in RA patient fibroblast-like synoviocytes and is implicated in RA progression, likely via specific binding of LMWHA4,5. Studies have also found increases in the HA-degrading enzyme KIAA1199 (aka CEMIP or HYBID) and LMWHA in both serum and synovial fluids of RA patients6. This increase in LMWHA is likely due to KIAA1199 as it has been shown to produce HA fragments of &lt; 100 kDa7.
<ol>
<li>Crowson C.S. et al. The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis and Rheumatism. 2011;63(3): 633-9.</li>
<li>Rudan I. et al. Prevalence of rheumatoid arthritis in low- and middle-income countries: A systematic review and analysis. Journal of Global Health. 2015;5(1): 010409.</li>
<li>Mateen S. et al. Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2016;455: 161-71.</li>
<li>Sulaiman W. et al. The trends of DMARDS prescribed in rheumatoid arthritis patients in Malaysia. Oman Medical Journal. 2009;24(4): 260-06.</li>
<li>Wu J et al. RHAMM induces progression of rheumatoid arthritis by enhancing the functions of fibroblast-like synoviocytes. BMC Musculoskeletal Disorders, 19:455 (2018).</li>
<li>Kouvidi K et al. Role of receptor for hyaluronic acid-mediated motility (RHAMM) in low molecular weight hyaluronan (LMWHA)-mediated fibrosarcoma cell adhesion. J. Biol.Chem. 286(44):38509-38520, 2011.</li>
<li>Kohi S et al. KIAA1199 is induced by inflammation and enhances malignant phenotype in pancreatic cancer. Oncotarget, 8(10): 17156-17163, 2017.</li>
</ol>
<h1 id="technology-overview">Technology Overview</h1>
Queen’s researchers have created novel N-acyl analogs of HA. Studies with N-butyrylated HA (BHA) have been found to prevent activation of TLR4 by either LMWHA or lipopolysaccharide on human macrophage cell lines. Furthermore, preclinical studies in gouty arthritis showed significant reduction of swelling, and speed of reduction of swelling, compared to prophylactic colchicine. Concurrent to those effects were significant reductions in pro-inflammatory cytokines and increases in anti-inflammatory cytokines. In follow-on they investigated effects of BHA on rheumatoid arthritis.
Low (0.05 mg/mL) concentrations of BHA significantly reduced the expression of pro-inflammatory cytokines (TNFα, IL-1β and IL-6) in an adjuvant‑induced arthritis (AIA) rat model (Figure 1), suggesting that BHA exhibits anti-inflammatory activity against cytokines produced by macrophages. This dosage of BHA showed a superior anti-inflammatory efficacy than positive control dexamethasone (DXMS), suggesting a promising role for BHA in the treatment of inflammation-related diseases.
<img src="https://s3-eu-west-1.amazonaws.com/assets.in-part.com/technologies/figures/daxBev3STA21lq8CWDlh_Figure-6A.png" alt="Figure 1: The Effects of BHA on Cytokine Levels in the Inflammatory Joint Tissues in AIA Rats" />
In addition to lowering cytokine levels, BHA was found to significantly decrease paw thickness, ankle circumference and arthritis scores (Figure 2). Interestingly, the lower dose of BHA provided a better overall effect than the positive control drug DXMS, suggesting that BHA can be an alternative treatment for RA without the side-effects of a weakened immune system caused by these corticosteroid drugs.
<img src="https://s3-eu-west-1.amazonaws.com/assets.in-part.com/technologies/figures/l3nmMwuhRLitZGBHgHui_BHA-alternative-figure.png" alt="Figure 2: Evaluation of the therapeutic effects of BHA in AIA rats." />
Anti‑inflammatory and antioxidant therapy has been shown to stop bone damage in RA patients1. BHA has been shown to reduce inflammation by inhibiting the production of pro‑inflammatory cytokines and regulate inflammatory signaling pathways while also reducing ROS levels. BHA was found to have better anti‑inflammatory and antioxidant effects than positive control drugs DXMS and GSH, respectively. BHA is a promising candidate for use as an anti‑inflammatory and antioxidant therapy with reduced side‑effects compared to current gold standard therapies. 
<img src="https://s3-eu-west-1.amazonaws.com/assets.in-part.com/technologies/figures/kR3V4wn0QpeWTW0yRSaN_figure12.png" alt="Figure 4: Effects of BHA on the expression of TNFα in LPS-induced RAW264.7 macrophage cells." />
<img src="https://s3-eu-west-1.amazonaws.com/assets.in-part.com/technologies/figures/WuUOS749RvqUx3Z6KYwJ_fig2.png" alt="Figure 5: Effects of AHA on the ROS level in LPS-induced RAW264.7 macrophages." />
<ol>
<li>Yang G. et al. Resveratrol alleviates rheumatoid arthritis via reducing ROS and inflammation, inhibiting MAPK signaling pathways, and suppressing angiogenesis. Journal of Agricultural and Food Chemistry. 2018;66(49): 12953-60.</li>
<li>Luan, X.; Cong, Z.; Anastassiades, T.P.; Gao, Y. N-Butyrylated Hyaluronic Acid Achieves Anti-Inflammatory Effects In Vitro and in Adjuvant-Induced Immune Activation in Rats. Molecules 2022, 27, 3267. <a href="https://doi.org/10.3390/molecules27103267">https://doi.org/10.3390/molecules27103267</a></li>
</ol>
<h1 id="benefits">Benefits</h1>
<ul>
<li>Superior anti‑inflammatory efficacy compared to dexamethasone</li>
<li>Superior anti‑oxidant efficacy compared to glutathione</li>
<li>Ability to treat RA through both anti‑inflammatory and antioxidant mechanisms</li>
</ul>
<h1 id="applications">Applications</h1>
<ul>
<li>Treatment of rheumatoid arthritis</li>
<li>Treatment of other inflammatory diseases, including osteoarthritis and nonalcoholic steatohepatitis (NASH)</li>
<li>Potential role as a cosmeceutical</li>
</ul>
<h1 id="opportunity">Opportunity</h1>
Seeking exclusive licensee, research collaborator or venture investment.