Vasculitis UK Funds 4 Research Projects in AAV, Other Vasculitis

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by Marta Figueiredo PhD |

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Vasculitis UK has awarded a total of £200,000 (about $283,000) in four grants to research projects mostly focused on the development of new therapeutic approaches and biomarkers for ANCA-associated vasculitis (AAV) and other vasculitis.

All grants, each about £50,000 (about $70,800), were given to researchers at academic institutions in the U.K.

Vasculitis is a group of disorders that occur when the immune system wrongly attacks blood vessels, leading to damage and swelling.

AAV is a type of vasculitis that affects small blood vessels due to the production of anti-neutrophil cytoplasmic autoantibodies (ANCAs), self-reactive antibodies that bind mainly to one of two proteins — proteinase 3 or myeloperoxidase (MPO) — present in neutrophils, a type of immune cell.

This abnormal immune attack on neutrophils promotes their activation and the release of toxic molecules, which recruits more neutrophils toward the site of damage and inflammation, perpetuating both of these processes.

Vasculitis UK periodically issues a call for research proposals. The latest application process ended on Jan. 31, 2020, and the review process was expected to be completed by mid-2020.

However, finding two suitable peer reviewers for each of the 11 submitted projects in the midst of the COVID-19 pandemic was “no easy feat,” Laura Whitty, Vasculitis UK’s research awards coordinator, said in a statement.

As such, the association decided to postpone the review process, which was restarted in November 2020, and the scientific advisory board decided the winners in February.

“We are delighted to announce that the following applicants received funding for their exciting and varied projects whose aims mirror Vasculitis UK’s priorities,” Whitty said.

One of the awarded projects, titled “Peptide Immunotherapy in experimental MPO-ANCA vasculitis,” will be led by Maria Prendecki, PhD, along with Steve McAdoo, PhD, both of Imperial College London.

During this 18-month project, researchers will use a rat model of AAV to analyze which part of the MPO protein is abnormally recognized by the immune system as foreign, prompting immune responses against it and causing damage. This type of information is expected to help better understand how to create immune tolerance to MPO.

Another award was given to a project focused on the identification of a biomarker able to predict relapses in AAV patients treated with rituximab. The research is being led by Rona Smith, MD, a clinical lecturer at the University of Cambridge.

Rituximab is an immunosuppressive therapy approved in the U.S. for treating granulomatosis with polyangiitis and microscopic polyangiitis, two subtypes of AAV. It works by killing B-cells, the immune cells that produce antibodies.

The therapy was originally marketed as Rituxan (by Biogen) in the U.S., Canada, and Japan, and MabThera (by Roche’s subsidiary Genentech) in Europe. A number of biosimilars have been approved in recent years.

Titled “Evaluation of CD27+ memory B cell reconstitution following rituximab maintenance therapy in ANCA associated vasculitis as a guide to future dosing,” the study will look at the levels of memory B-cells in 36 rituximab-treated AAV patients.

Memory B-cells are crucial to the immune system “remembering” microbes or foreign particles that the body was previously exposed to, therefore prompting a quick, highly specific response to the threat in case of re-exposure.

Therefore, memory B-cells are a key contributor to the abnormal immune responses that characterize autoimmune diseases, such as AAV, and their absence is thought to be associated with lower disease severity.

By closely analyzing the return of memory B-cells in the bloodstream after rituximab-induced B-cell depletion, the researchers hope to identify a biomarker that reliably predicts an imminent flare.

This potential biomarker may be used in combination with other factors in a relapse prediction model and in future studies to guide the optimal timing of subsequent rituximab doses.

David Jayne, MD, director of the Vasculitis and Lupus Service at Addenbrooke’s Hospital, Cambridge University Hospitals, and Mark McClure, clinical research associate in Jayne’s lab, will be co-leaders of the project.

A team of researchers at University of Nottingham also received a grant to develop the project “Incidence of cardiovascular events and common cancers in ANCA-associated vasculitis and Takayasu’s arteritis in the English population.”

After having identified U.K. patients living with AAV and Takayasu’s arteritis, a rare form of vasculitis involving inflammation in the body’s largest arteries, the team will add these patients to the National Congenital Anomaly and Rare Disease Registration Service.

This will allow researchers to analyze the healthcare data of patients to determine whether they have a greater risk of cardiovascular problems (heart disease, strokes, and blood clots) and common types of cancer (breast, prostate, lung, bowel, and bladder), compared with age- and sex-matched unaffected individuals.

The project will be led by Megan Rutter, along with colleagues Fiona Pearce, PhD, Peter Lanyon, and Richard Hubbard, MD, GSK/British Lung Foundation professor of respiratory epidemiology.

Another grant was given to a preclinical project that seeks to identify an effective and targeted therapy for STING-associated vasculitis with onset in infancy, a rare, life-threatening genetic form of vasculitis causing severe inflammation throughout the body, especially in the skin, blood vessels, and lungs.

The project, “Preclinical studies to develop an RNA targeting novel genetic therapy for STING-associated vasculitis with onset in infancy,” will have a duration of one year and will be led by Despina Eleftheriou, PhD, assistant professor of pediatric rheumatology at University College London’s Great Ormond Street Hospital.

Co-leaders include Paul Brogan, PhD, Haiyan Zhou, MD, PhD, and Philip Hawkins, PhD.

In April, Vasculitis UK also funded a research project investigating how people with AAV and other vasculitis respond to COVID-19 vaccines.