Blood Test Could Reveal When Rheumatoid Arthritis Will Strike – Howard Hughes Medical Institute

Scientists have identified a new type of cell that appears in the bloodstream of rheumatoid arthritis patients shortly before joint inflammation flares.

A never-before-seen cell type could forewarn of rheumatoid arthritis symptoms.

The cells, dubbed PRIME cells, accumulate in the blood during the week prior to disease flare-ups, Howard Hughes Medical Institute Investigator Robert Darnell's team reports July 15, 2020, in the New England Journal of Medicine. The findings could lead to better prediction of when severe pain and swelling, called flares will occur, as well as provide new avenues for treatment.

PRIME cells are one thing you might want to target to arrest the flare before it happens, Darnell says. Thats the ideal of medical science to know enough about a disease that you can put your finger on whats about to make someone sick.

Rheumatoid arthritis is a disease of the immune system that causes inflammation in the joints, especially around the hands and feet. It can be debilitating and frequently strikes people in their 30s or 40s. The symptoms come in waves, with stretches of relative quiet interspersed with painful flares. Current therapeutics, chiefly steroids, can treat these symptoms, but theres no cure.

To study this sort of disease, where symptoms vary dramatically from week to week, its critical to track changes in the body over an extended time. But its hard for patients to trek to a clinic for frequent testing. So Darnell, a neuro-oncologist at the Rockefeller University, and his colleagues developed an at-home blood collection system. Patients with rheumatoid arthritis did simple finger sticks and sent their blood to his lab. Each participant also kept a record of symptoms to identify when flares occurred.

PRIME cells are one thing you might want to target to arrest the flare before it happens.

Robert Darnell, HHMI Investigator at The Rockefeller University

Armed with these records, the researchers tested the blood samples, looking for molecular changes preceding the onset of symptoms. By analyzing the RNA of cells in the bloodstream, Darnells team could identify which types of cells were present during symptom-free times and in the weeks preceding a flare.

In samples collected two weeks prior to a flare, researchers saw an increase in immune cells called B cells. Thats not surprising, Darnell says researchers already knew these cells attacked patients joints in rheumatoid arthritis.

But in samples collected one week before a flare, his team noticed something odd. They saw an increase in RNA that didnt match the genetic signature of any known type of blood or immune cell. That got us thinking there was something fishy going on, says study coauthor Dana Orange, a rheumatologist at Rockefeller. The RNA signature instead resembled that of bone, cartilage, or muscle cells cells not typically found in the blood.

Darnells team called the newfound cell type a PRIME cell, for pre-inflammation mesenchymal cell. (Mesenchymal cells are a type of stem cell that can develop into bone or cartilage.) In the patients, PRIME cells accumulated in the bloodstream a week before the flare but disappeared during the flare. This observation, combined with previous work from another lab in mice, suggests a possible role for PRIME cells in rheumatoid arthritis flares, Darnell says.

One of the teams next steps is to test in more patients whether the presence of these cells can predict a flare, Darnell says. The researchers are still recruiting patients for this study; currently the teams blood collection system is only available for use in research. Darnell also wants to study PRIME cells molecular characteristics. If the cells do indeed take part in causing flares, he says, understanding the unique aspects of PRIME cells might enable us to target them with a drug and get rid of them.

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Citation

Dana E. Orange et al. RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares, New England Journal of Medicine. Published online July 15, 2020. doi: 10.1056/NEJMoa2004114

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Blood Test Could Reveal When Rheumatoid Arthritis Will Strike - Howard Hughes Medical Institute

U of T spin-off Empirica Therapeutics acquired by US firm – News@UofT

Empirica Therapeutics, a startup co-founded by Donnelly Centre investigatorJason Moffathas beenacquired by Century Therapeutics, a U.S. based company developing off-the-shelf cell therapy products for cancer.

Century will develop Empiricas proof-of-principle treatment for glioblastoma, an aggressive form of brain cancer, into therapy that can be tested on patients.

Moffat co-founded Empirica in 2018 with Dr. Sheila Singh, professor in the department of surgery at McMaster University, to leverage their combined expertise in cell engineering, functional genomics and brain tumour modelling. The teams recently demonstrated the potential of CAR-T cell therapy, in which immune cells are instructed to kill tumour cells, for the treatment of glioblastoma in preclinical models, as published in a May 2020Cell Stem Cellpaper.

Recent advances in immunotherapy have offered hope to patients with previously untreatable cancers, says Moffat, a professor of molecular genetics at U of T and the Canada Research Chair in Functional Genomics of Cancer who served as Empiricas chief scientific officer. We hope that our approach of specifically targeting glioblastoma cells with CAR-T therapy will give the patients a better quality of life and increase their chances of survival.

Philadelphia-based Century Therapeutics will further develop this type of treatment for patients. Backed by Bayer, Fujifilm, and Versant Ventures, the company specializes in developing cell therapies from induced pluripotent stem cells (iPSCs) that have been genetically engineered to avoid immune rejection. Century is working to harness the power of stem cells to develop curative cell therapy products for cancer that overcome the limitations of first-generation cell therapies. The companys CEO, Lalo Flores, acknowledged Empiricas deep expertise and unique capabilities that will accelerate their efforts to develop iPSC derived immune effector cell products designed to treat brain cancer.

Chimeric antigen receptor T cell (CAR-T) therapy involves genetically engineering a patients immune T cells to target and bind to a specific protein present on cancer cells directly and eliminate them. Centurys technology skirts the need to collect patients own immune cells thanks to its ability to manufacture off-the-shelf T cells that can be implanted without rejection.

Our team is excited to become part of Century Therapeutics, whose iPSC-derived allogeneic cell therapy platform is creating promising treatments for patients who need them most, says Dr. Singh, who is also a Canada Research Chair in Human Cancer Stem Cell Biology and served as Empiricas chief executive officer.

Now known as Century Therapeutics Canada, the new subsidiary will be based at McMaster Innovation Park.

Empiricas first CAR-T program was focused on a protein called CD133, which was the first brain tumor initiating cell marker discovered by Singh while a PhD student at the University of Toronto. Subsequent work by both the Singh and Moffat groups led to a deeper functional understanding of CD133 and an antibody that proved useful for marking cells for therapy.

When used in mice with human glioblastoma, CD133-targetting CAR-T therapy was considered a success due to reduced tumor burden and improved survival. These pre-clinical results were partly supported by a Terry Fox Research Institute New Frontiers Program Project Grant awarded to a multidisciplinary team of scientists including Singh and Moffat.

Glioblastoma is the most common and aggressive form of brain cancer owing to tumour heterogeneity at the molecular level and its ability to evolve into new forms that resist therapy. Standard treatment involves surgery, radiation and chemotherapy but most patients relapse within seven to nine months, while median survival between diagnosis and death has not extended beyond 16-20 months over the past decade.

CAR-T will be delivered in recurrent glioblastoma patients after Moffat and Singhs teams found that a population of CD133 positive glioblastoma cells remain following initial treatment.

If we can hit those cells at minimal disease, we should buy the patient more time, says Moffat. And hopefully well find a way to figure out how to combine multiple CAR-Ts; for example, by combining CD133 and other targets to potentially even cure the disease.

Empirica Therapeutics was supported by investments from U of Ts strategic partners, the Centre for Commercialization of Antibodies and Biologics and the Centre for Commercialization of Regenerative Medicine.

We are proud to have been involved with the launch and growth of Empirica, stated Rob Verhagen, former CEO of CCAB. The outcome with Century marks another stride in building a productive life science industry at U of T and McMaster and we look forward to seeing this valuable research benefiting patients in the future. The startup was also supported by the McMaster Industry Liaison Office and the Ontario Bioscience Innovation Organization through important connections to relevant business networks and partners.

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Video: The Science Of Cannabis And CBD With Four Leading Experts – Benzinga

While there is mounting anecdotal evidence on the therapeutic benefits of cannabis and CBD, including their anti-inflammatory and anxiolytic effects, we still dont fully understand the underlying biological mechanisms leading to their efficacy, or why they can be effective for some people, but not for others.

Groundbreaking new human studies from UC San Diego, University of Utah, and the Wholistic Research and Education Foundationare about to change all that:

Watch the expert panel put together by Trailblazers, moderated by Benzinga Cannabis Managing Director and El Planteo CEO Javier Hasse, to learn about the cutting edge, multidisciplinary studies underway to explore just how cannabis and CBD deliver their diverse health benefits.

Photo: Pelin Thorogood announcing the Trailblazers Partnership with Wholistic Foundation August 18, 2019 with , Dr. Jeff Chen , Dr. Jeff Anderson, and Tyler Wakstein.

2020 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.

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