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Thursday, June 23, 2022

Calithera Starts Phase 2 Trial of Mivavotinib in Large B-Cell Lymphoma

  Calithera Biosciences, Inc.,  (Nasdaq: CALA), a clinical-stage, precision-oncology biopharmaceutical company, announced that the first patient has been enrolled in a multicenter phase 2 clinical trial evaluating its spleen tyrosine kinase (SYK) inhibitor mivavotinib (CB-659) in patients with relapsed/refractory non-germinal center B-cell like (non-GCB) diffuse large B-cell lymphoma (DLBCL), a DLBCL subpopulation that primarily comprises patients with activated B-cell like disease (ABC).

In a retrospective analysis of prior phase 1/2 studies in patients with DLBCL, patients with non-GCB DLBCL who received mivavotinib had a response rate of 53%, as compared to a response rate of 22% in patients with GCB DLBCL. Additionally, recent preclinical studies have shown enhanced SYK activity, and greater sensitivity to SYK inhibition, in DLBCL tumor-cell lines with mutations in MYD88 and CD79b genes. A significant fraction of patients with non-GCB DLBCL have tumors that harbor these mutations, and this subset of patients is known to have poorer outcomes with standard-of-care therapies.

https://www.biospace.com/article/releases/calithera-biosciences-announces-first-patient-enrolled-in-phase-2-clinical-trial-of-mivavotinib-in-relapsed-refractory-non-gcb-abc-diffuse-large-b-cell-lymphoma-/

AbbVie Redeems Priority Review Voucher for Rinvoq Approval

 On Thursday afternoon, the U.S. Food and Drug Administration published in the Federal Register that AbbVie has redeemed a Rare Pediatric Disease Priority Review Voucher for Rinvoq (upadactinib). The FDA approved the drug in March for adults with moderately to severely active ulcerative colitis (UC) who didn’t respond adequately or were intolerant to one or more tumor necrosis factor (TNF) blockers.

Priority review vouchers (PRVs) allow the recipient to expedite the review of one of its new drug products. The products can also be sold to other companies for whatever amount of cash they can get for them.

This program is a way to incentivize the development of new drugs for historically underserved conditions, and it allows the holder of the PRV to speed the review process. A standard review process is about 10 months, but a PRV can cut that to six months, which may be used by a company to get a head-start on marketing a drug.

Although neither AbbVie nor the FDA is obligated to say where the PRV came from, it’s possible that it was the PRV AbbVie acquired from Eiger BioPharmaceuticals for $95 million in November 2020. The PRV had been granted to Eiger as the result of the FDA approval of Zokinvy (lonafarnib) for treatment of Progeria and processing-deficient Progeroid Laminopathies. The drug is indicated in both adults and pediatric patients 12 months and older, which would justify the Rare Pediatric Disease PRV.

AbbVie and Rinvoq have a history of using PRVs. In 2015, AbbVie acquired a Rare Pediatric Disease Priority Review Voucher from United Therapeutics. United received the PRV when Unituxin was approved in the U.S. for neuroblastoma, a rare pediatric disease. AbbVie invested a whopping $350 million for the PRV. Rinvoq was approved first for moderate to severe rheumatoid arthritis in 2019, and reportedly, the company used the United PRV to get an accelerated review.

Rinvoq has been approved for RA, active psoriatic arthritis when TNF blockers didn’t work, and for severely active UC when one or more TNF blockers didn’t work. The approval for ulcerative colitis was the first for the drug in gastroenterology. It was based on data from three Phase III trials, U-ACHIEVE and U-ACCOMPLISH, induction studies that evaluated the drug at 45 mg once a day for eight weeks, and then 15 mg or 30 mg once a day for the maintenance study, U-ACHIEVE maintenance, through 52 weeks.

All the studies demonstrated that patients receiving the drug met clinical remission at weeks eight and 52, which was the primary endpoint. The studies also hit all ranked secondary endpoints, including endoscopic improvement and histologic-endoscopic mucosal improvement (HEMI).

During AbbVie's 2021 annual report, the company confirmed previous revenue guidance on Rinvoq, projecting $7.5 billion in sales by 2025. In 2021, it brought in $1.651 billion.

AbbVie is leaning heavily on Rinvoq and another relatively new drug, Skyrizi, to fill in the gap when its mega-blockbuster drug, Humira, loses patent protection. Humira brought in a jaw-dropping $20.694 billion in adjusted net revenues in 2021, but it will lose its patent exclusivity in 2023. Numerous companies have biosimilar drugs poised for marketing the minute the patent coverage falls.

“Skyrizi and Rinvoq will be commercialized across all of Humira’s major indications — plus atopic dermatitis,” Rick Gonzalez, AbbVie’s Chairman and CEO, said at the company’s annual report conference call. “We expect combined peak sales for Skyrizi and Rinvoq to exceed the peak revenues achieved by Humira.”

https://www.biospace.com/article/abbvie-redeems-priority-review-voucher-to-expand-rinvoq-approval-/

ALS may be linked to both immune and central nervous systems

 The immune system may play a fundamental role along with the central nervous system in amyotrophic lateral sclerosis (ALS), also known as "Lou Gehrig's disease," Mount Sinai researchers report. Their study, published on June 22 in Nature, could have significant implications for diagnosing and treating the devastating neurodegenerative disease.

Until now, studies of ALS have focused on the central nervous system. But the Mount Sinai team reported both immune and nervous system dysfunctions in animal models and patients with ALS4, a juvenile and slowly progressive form of ALS, which is caused by mutations in the gene SETX.

"We learned that mutations in SETX need to be expressed in both the nervous and immune systems to generate motor impairment in mice, and that dysfunction in the adaptive immune system characterizes ALS4 in mice as well as humans," says Laura Campisi, PhD, Assistant Professor of Microbiology at the Icahn School of Medicine at Mount Sinai, and co-lead author of the study with Ivan Marazzi, PhD, Associate Professor of Microbiology at Icahn Mount Sinai.

Further evidence of immune system involvement, she adds, was detected in the high concentration of CD8 T cells -- which are usually involved in the destruction of tumors and cells in the body that harbor pathogens -- in the spinal cord and peripheral blood of ALS4 mice and patients. Those increased CD8 T cell populations, known as TEMRA (terminally differentiated effector memory), correlate with ALS4 disease progression.

ALS is characterized by the progressive death of motor neurons, which severely impacts the functional ability of patients in a host of ways, including preventing the movement of arms and legs, speech, swallowing, and, eventually, breathing. There is no treatment or cure for ALS. Researchers have focused their efforts over the years on neurons, though more recent studies have shown evidence of interaction between the central nervous and immune systems, long considered separate compartments.

The Mount Sinai study, in collaboration with neurobiologist Albert La Spada, MD, PhD, from the University of California, Irvine, is one of the first to address whether the adaptive immune system, which builds up the body's protection as it is exposed to foreign pathogens, could be linked to some forms of ALS.

"There is a great need to understand if neurodegeneration is caused or aggravated by immune dysfunction," explains Dr. Campisi.

For their study, researchers analyzed mice and human samples with state-of-the-art technologies like mass and spectral cytometry and single-cell sequencing. "Our finding that peculiar immune signatures distinguish different forms of ALS could be significant for designing 'personalized' treatments tailored to specific subgroups of patients," she notes.

An added advantage is that dysfunctional CD8 T cells linked to ALS4 can be detected in the peripheral blood, which is easily accessible compared to cerebrospinal fluid, which requires an invasive procedure for collection. Another observation by the Mount Sinai team -- that TEMRA CD8 T cells associated with ALS4 protect mice against glioma, a type of cancer that occurs in the brain -- opens the door to further therapeutic research in this area.

"Our discovery of a link between the immune and central nervous systems in ALS4 disease has immediate implications for other types of ALS, other neurodegenerative disorders, and for cancer," said Dr. Marazzi. "In addition to making important inroads into the pathogenesis of ALS, our work underscores the pioneering work of Mount Sinai researchers in the fields of neuroscience and immunology."


Story Source:

Materials provided by The Mount Sinai Hospital / Mount Sinai School of MedicineNote: Content may be edited for style and length.


Journal Reference:

  1. Laura Campisi, Shahab Chizari, Jessica S. Y. Ho, Anastasia Gromova, Frederic Arnold, Lorena Mosca, Xueyan Mei, Yesai Fstkchyan, Denis Torre, Cindy Beharry, Marta Garcia-Forn, Miguel Jiménez-Alcázar, Vladislav A. Korobeynikov, Jack Prazich, Zahi A. Fayad, Marcus M. Seldin, Silvia De Rubeis, Craig L. Bennett, Lyle W. Ostrow, Christian Lunetta, Massimo Squatrito, Minji Byun, Neil A. Shneider, Ning Jiang, Albert R. La Spada, Ivan Marazzi. Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4Nature, 2022; DOI: 10.1038/s41586-022-04844-5

Cancer survivors grew to 18M in US, over 2/3 age 65 and up

 A new report led by researchers at the American Cancer Society (ACS) in collaboration with the National Cancer Institute (NCI) shows more than 18 million Americans (8.3 million males and 9.7 million females) with a history of cancer were living in the United States as of January 1, 2022, with a little over 12 million (67%) aged 65 years or older. The study also found substantial racial disparities in treatment and survival for common cancers. The findings were published today as an article in CA: A Cancer Journal for Clinicians and a companion consumer version, Cancer Treatment & Survivorship Facts & Figures 2022-2024.

To assist the public health community in better serving cancer survivors, the ACS and the NCI collaborate every three years to estimate cancer prevalence in the U.S. The most prevalent cancers are prostate (3,523,230), melanoma of the skin (760,640), and colorectal (726,450) among men and breast (4,055,770), uterine corpus (891,560), and thyroid (823,800) among women. More than one-half (53%) of survivors were diagnosed within the past 10 years.

As the population of cancer survivors continues to grow and age, there is an increased need for guidance for health professionals, caregivers, and patients on how to manage late and long-term effects of cancer and its treatment, maintain healthy behaviors and limit financial toxicity," said Kimberly Miller, scientist, surveillance and health equity science at the ACS and lead author of the study. "In addition, the survivor population is increasingly diverse, and further resources are needed to ensure equitable access to survivorship care."

According to the report, contemporary treatment patterns based on information from the National Cancer Database show evidence of increased uptake of recent treatment advances. For example, receipt of immunotherapy for stage IV non-small cell lung cancer increased from 12% in 2016 to 33% in 2018.

However, there are substantial racial disparities in treatment. For example, receipt of surgery is substantially lower among Black patients than White patients with non-small cell lung cancer, 49% versus 55% for stages I-II and 16% versus 22% for stage III. One of the largest racial disparities occurs in the treatment of rectal cancer, for which only 41% of Black patients with stage I disease receive proctectomy or proctocolectomy compared to 66% of White patients. Treatment disparities are exacerbated by later stage diagnosis in Black people than in White people for most cancers, with one of the largest disparities for uterine corpus cancer (59% vs 73% diagnosed with stage I disease, respectively).

"We are encouraged by a growing number of tools to assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship," said Miller. For example, the ACS has developed guidelines for posttreatment care and nutrition and physical activity among survivors. "However, more evidence-based strategies and equitable access to available resources are needed to mitigate disparities for communities of color."

The study authors add that the increasing number of cancer survivors cannot be used as a measure of progress by itself against cancer because the increase in part reflects population growth. In addition, these estimates do not reflect the impact of the COVID-19 pandemic, as they are based on observed population-based data through 2018.


Story Source:

Materials provided by American Cancer SocietyNote: Content may be edited for style and length.


Journal Reference:

  1. Kimberly D. Miller, Leticia Nogueira, Theresa Devasia, Angela B. Mariotto, K. Robin Yabroff, Ahmedin Jemal, Joan Kramer, Rebecca L. Siegel. Cancer treatment and survivorship statistics, 2022CA: A Cancer Journal for Clinicians, 2022; DOI: 10.3322/caac.21731

Weather forecasting methods can be adapted to assess risk of COVID-19 exposure

 Techniques used in weather forecasting can be repurposed to provide individuals with a personalized assessment of their risk of exposure to COVID-19 or other viruses, according to new research published by Caltech scientists.

The technique has the potential to be more effective and less intrusive than blanket lockdowns for combatting the spread of disease, says Tapio Schneider, the Theodore Y. Wu Professor of Environmental Science and Engineering; senior research scientist at JPL, which Caltech manages for NASA; and the lead author of a study on the new research that was published by PLOS Computational Biology on June 23.

"For this pandemic, it may be too late," Schneider says, "but this is not going to be the last epidemic that we will face. This is useful for tracking other infectious diseases, too."

In principle, the idea is simple: Weather forecasting models ingest a lot of data -- for example, measurements of wind speed and direction, temperature, and humidity from local weather stations, in addition to satellite data. They use the data to assess what the current state of the atmosphere is, forecast the weather evolution into the future, and then repeat the cycle by blending the forecast atmospheric state with new data. In the same way, disease risk assessment also harnesses various types of available data to make an assessment about an individual's risk of exposure to or infection with disease, forecasts the spread of disease across a network of human contacts using an epidemiological model, and then repeats the cycle by blending the forecast with new data. Such assessments might use the results of an institution's surveillance testing, data from wearable sensors, self-reported symptoms and close contacts as recorded by smartphones, and municipalities' disease-reporting dashboards.

The research presented in PLOS Computational Biology is proof of concept. However, its end result would be a smart phone app that would provide an individual with a frequently updated numerical assessment (i.e., a percentage) that reflects their likelihood of having been exposed to or infected with a particular infectious disease agent, such as COVID-19.

Such an app would be similar to existing COVID-19 exposure notification apps but more sophisticated and effective in its use of data, Schneider and his colleagues say. Those apps provide a binary exposure assessment ("yes, you have been exposed," or, in the case of no exposure, radio silence); the new app described in the study would provide a more nuanced understanding of continually changing risks of exposure and infection as individuals come close to others and as data about infections is propagated across a continually evolving contact network.

The idea was born in the early days of the COVID-19 pandemic, when colleagues and partners Schneider and Chiara Daraio, the G. Bradford Jones Professor of Mechanical Engineering and Applied Physics and Heritage Medical Research Institute Investigator, abruptly found themselves isolating at home and wondering how to use their scientific and engineering expertise to help the world deal with this new threat.

One pre-pandemic focus of Daraio's research was the development of low-cost body temperature trackers. And that raised the question: Would the widespread use of such trackers allow for better tracking and understanding of COVID-19's spread?

"We were envisioning something like a weather forecasting app, harnessing information from sensors, infection data, and proximity tracking, which people could use to adjust their behavior to mitigate individual risks," says Daraio, co-author of the PLOS Computational Biology paper.

Schneider is a climate scientist who helms the Climate Modeling Alliance (CliMA), which is leveraging recent advances in the computational and data sciences to develop a wholly new climate model. He reached out to longtime acquaintance Jeffrey Shaman of Columbia University. Shaman's research on how climate change affects the spread of infectious diseases led Shaman to an interest in epidemiology and the adaptation of similar weather-forecasting methods for disease modeling on the community level.

"Over the last decade, the field of infectious-disease modeling, and forecasting in particular, has exploded. Many disease-forecasting approaches leverage ensemble and inference methods commonly used in weather prediction," says Shaman, co-author of the PLOS Computational Biology paper.

The team had two key challenges: adapting weather-prediction methods for this purpose and developing a realistic test bed to gauge how well it works.

"Conceptually it is a very appealing idea, as methods to forecast weather have been so effective in predicting the chaotic atmosphere, a famously challenging task," says Caltech research scientist Oliver Dunbar. "But there is no direct translation. An epidemic-forecasting app has very little data to work with and only on a partial population of users. We fortunately found success by coupling this sparse data with the latest smart-device technologies and a mathematical viral spreading model."

To test it, the team turned to Lucas Böttcher of the Frankfurt School of Finance and Management in Germany. Böttcher built a computer model of an imaginary city -- a downscaled and idealized version of New York City -- with 100,000 "nodes," or fictional people, and then studied how well the adapted weather-forecasting methods predicted the spread of a disease through the population.

The results were encouraging: in the simulations, the model identified up to twice as many potential exposures than would be caught by traditional contact tracing or exposure-notification apps when both use the same data.

"The methods developed in our study are relevant not only in the context of infectious disease management, but they also open up new ways of combining observation data with high-dimensional mechanistic models arising in computational biology," says Böttcher, co-author of the PLOS Computational Biology paper.

Despite these promising results, the implementation of this technology in the real world requires suitable levels of smart-device users, and effective testing campaigns to make the risk-assessment software work for managing and controlling epidemics. If approximately 75 percent of a given population provide relevant information (for example, whether they have tested positive for a disease) and self-isolate when they may have been exposed, the risk-assessment software is accurate enough to manage and control the COVID epidemic through the entire population. And yet, as is evident by COVID-19 vaccination rates, buy-in by such a large fraction of the population is difficult to achieve.

Nevertheless, a promising scenario is deployment by smaller community user bases -- for example, the population of a college campus -- that can readily provide the software with more than enough data to provide accurate risk assessments that will locally reduce the spread of disease.

"The challenge in making this system a reality is managing privacy concerns, for example, about transferring data about close contacts to a central data-processing facility," Schneider says. "That being said, only anonymized information is needed. Location information is already routinely collected for commercial use, and we envision ways to harden the system against exploitation by bad actors."

Other co-authors of the PLOS Computational Biology paper include Caltech research scientist Jinlong Wu and graduate student Dmitry Burov as well as former Caltech postdoc Alfredo Garbuno-Iñigo of Instituto Tecnológico Autónomo de México; Gregory Wagner and Raffaele Ferrari of MIT (all members of CliMA); and Sen Pei of Columbia University. This research was supported by Eric and Wendy Schmidt and Schmidt Futures; the Swiss National Science Foundation; the National Institutes of Health; the Army Research Office; the National Science Foundation; the National Institute of Allergy and Infectious Diseases; and the Morris-Singer Foundation.


Story Source:

Materials provided by California Institute of Technology. Original written by Robert Perkins. Note: Content may be edited for style and length.


Journal Reference:

  1. Tapio Schneider, Oliver R. A. Dunbar, Jinlong Wu, Lucas Böttcher, Dmitry Burov, Alfredo Garbuno-Inigo, Gregory L. Wagner, Sen Pei, Chiara Daraio, Raffaele Ferrari, Jeffrey Shaman. Epidemic management and control through risk-dependent individual contact interventionsPLOS Computational Biology, 2022; 18 (6): e1010171 DOI: 10.1371/journal.pcbi.1010171

Unique underlying molecular factors driving melanoma development

 A new study reveals important molecular information that could help scientists develop more effective treatment and prevention strategies for a difficult-to-treat form of melanoma skin cancer.

In this new report, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) researchers identify and describe key features of a gene mutation responsible for 15 to 20% of all melanomas.

Using a preclinical laboratory model, the team establishes that the frequency at which a specific NRAS gene mutation occurs in human melanoma is directly related to the ability of that gene mutation to initiate spontaneous melanoma formation.

“This means that properties of the mutant itself – rather than the ease at which that specific gene mutation occurs – is the cause of cancer formation,” said corresponding author Christin Burd who serves an associate professor of molecular genetics in The Ohio State University College of Arts and Sciences, Department of Molecular Genetics and a member of the OSUCCC – James Molecular Carcinogenesis and Chemoprevention Program.

NRAS-mutant cancers are challenging to treat because effective therapies beyond immunotherapy don’t exist yet,” said Burd. “Each cancer type seems to prefer a specific ‘flavor’ of mutant NRAS, and it has not been clear why this is.”

The OSUCCC – James wanted to know what made the melanoma-promoting NRAS mutants different than those that promote other cancer types. Scientists say this knowledge could help investigators pinpoint the early events required for melanoma formation and develop treatments that prevent the disease.

Burd and colleagues report their findings in the June 7, 2022, issue of Nature Communications.

Study design and methods
To conduct this study, OSUCCC – James researchers developed genetically engineered models that would allow them to activate one of nine different NRAS-mutant variations in melanocytes, the pigment cells that form melanoma.

“Amazingly, when we activated these gene mutations only those found in the human disease caused melanoma to develop,” said Burd. “Some mutants never led to melanoma, yet we know that they cause leukemia. This finding shows that selection of NRAS mutations is specific to each tumor type and occurs during cancer initiation, rather than in response to a specific mutagenic event like sun exposure.”

Collaborating with Sharon Campbell, a structural biologist at the University of North Carolina (UNC) Chapel Hill, and Debbie Morrison at the National Institutes of Health, Burd’s team identified that slight variances in the outward facing structure of NRAS mutants capable of initiating melanoma that made these proteins better able to interact with the signaling pathways that drive melanoma growth.

 

“Now we will work to target this unique structural feature of the melanoma-inducing NRAS mutants to prevent and/or treat the disease,” said Burd. “Our work also demonstrates and confirms what was – until now – only speculation: that minor differences between the RAS mutants determine which ‘flavors’ can cause a particular cancer. Such a concept could be used to find vulnerabilities in other RAS-driven tumor types.”

To facilitate similar discoveries, the team generated eight new and publicly available genetically engineered mouse models that will serve as an essential toolkit for the entire RAS community. Burd says these models can be used to activate and study the role of NRAS is other relevant cancer types such as colon cancer, leukemia, myeloma, and thyroid cancer. They can also be used to investigate new drugs for these diseases.

This research was supported with funding from the Damon Runyon Foundation and the Pelotonia Graduate Fellowship of study coauthor Brandon Murphy, who is now a postdoctoral fellow at the University of Utah.

The preclinical research models developed in Burd’s lab and used for this research are publicly available to scientists conducting research about other RAS-driven cancer types or working to develop new cancer therapies through the National Institute of Health’s repository.

Additional study coauthors include Elizabeth M. Terrell, Venkat R. Chirasani, Tirzah J. Weiss, Rachel E. Lew, Andrea M. Holderbaum, Aastha Dhakal, Valentina Posada, Marie Fort, Michael S. Bodnar, Leiah M. Carey, Min Chen, Craig J. Burd, Vincenzo Coppola and Sharon L. Campbell.

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Media Contact:
Amanda Harper | OSUCCC – James | Media Relations
614-685-5420 | Amanda.Harper2@osumc.edu

Surprising link between immune system, hair growth

 Salk scientists have uncovered an unexpected molecular target of a common treatment for alopecia, a condition in which a person’s immune system attacks their own hair follicles, causing hair loss. The findings, published in Nature Immunology on June 23, 2022, describe how immune cells called regulatory T cells interact with skin cells using a hormone as a messenger to generate new hair follicles and hair growth.

“For the longest time, regulatory T cells have been studied for how they decrease excessive immune reactions in autoimmune diseases,” says corresponding author Ye Zheng, associate professor in Salk’s NOMIS Center for Immunobiology and Microbial Pathogenesis. “Now we’ve identified the upstream hormonal signal and downstream growth factor that actually promote hair growth and regeneration completely separate from suppressing immune response.”

 

The scientists didn’t begin by studying hair loss. They were interested in researching the roles of regulatory T cells and glucocorticoid hormones in autoimmune diseases. (Glucocorticoid hormones are cholesterol-derived steroid hormones produced by the adrenal gland and other tissues.) They first investigated how these immune components functioned in multiple sclerosis, Crohn’s disease and asthma.

 

They found that glucocorticoids and regulatory T cells did not function together to play a significant role in any of these conditions. So, they thought they’d have more luck looking at environments where regulatory T cells expressed particularly high levels of glucocorticoid receptors (which respond to glucocorticoid hormones), such as in skin tissue. The scientists induced hair loss in normal mice and mice lacking glucocorticoid receptors in their regulatory T cells.

 

“After two weeks, we saw a noticeable difference between the mice—the normal mice grew back their hair, but the mice without glucocorticoid receptors barely could,” says first author Zhi Liu, a postdoctoral fellow in the Zheng lab. “It was very striking, and it showed us the right direction for moving forward.”

 

The findings suggested that some sort of communication must be occurring between regulatory T cells and hair follicle stem cells to allow for hair regeneration.

 

Using a variety of techniques for monitoring multicellular communication, the scientists then investigated how the regulatory T cells and glucocorticoid receptors behaved in skin tissue samples. They found that glucocorticoids instruct the regulatory T cells to activate hair follicle stem cells, which leads to hair growth. This crosstalk between the T cells and the stem cells depends on a mechanism whereby glucocorticoid receptors induce production of the protein TGF-beta3, all within the regulatory T cells. TGF-beta3 then activates the hair follicle stem cells to differentiate into new hair follicles, promoting hair growth. Additional analysis confirmed that this pathway was completely independent of regulatory T cells’ ability to maintain immune balance.

 

However, regulatory T cells don’t normally produce TGF-beta3, as they did here. When the scientists scanned databases, they found that this phenomenon occurs in injured muscle and heart tissue, similar to how hair removal simulated a skin tissue injury in this study.

 

“In acute cases of alopecia, immune cells attack the skin tissue, causing hair loss. The usual remedy is to use glucocorticoids to inhibit the immune reaction in the skin, so they don't keep attacking the hair follicles,” says Zheng. “Applying glucocorticoids has the double benefit of triggering the regulatory T cells in the skin to produce TGF-beta3, stimulating the activation of the hair follicle stem cells.”

 

This study revealed that regulatory T cells and glucocorticoid hormones are not just immunosuppressants but also have a regenerative function. Next, the scientists will look at other injury models and isolate regulatory T cells from injured tissues to monitor increased levels of TGF-beta3 and other growth factors.  

 

This work was supported by a NOMIS fellowship and the NOMIS Foundation, the National Institute of Health (NCI CCSG P30-014195, NIA P01- 454 AG073084, NIA-NMG RF1-AG064049, NIA P30-AG068635, R01-AI107027, R01-AI1511123, R21-AI154919, and S10-OD023689), the Leona M. and Harry B. Helmsley Charitable Trust, the Crohn’s and Colitis Foundation, the National Cancer Institute, and Salk’s Cancer Center Core Facilities (P30-CA014195).

 

Other authors included Xianting Hu, Yuqiong Liang, Jingting Yu, and Maxim N. Shokhirev of Salk; and Huabin Li of Fudan University in Shanghai.

 

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk’s mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer’s, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.