Trichohepatoenteric Syndrome

A rare subtype of the world's most common parasite, Blastocystis, has been found to produce a unique by-product of its metabolism, which can cause gut inflammation under normal gut conditions. The human gut -- or gastrointestinal system -- where food is broken down into nutrients for the body, is an ecosystem that harbours thousands of bacteria species. While some microorganisms are harmful, many are beneficial and help keep the human body in good health. Besides bacteria, the gut microbiota also consists of other types of microorganisms, including protists, yeasts, and viruses. Blastocystis, the world's most common protist-a form of unicellular microscopic organism-in the gut, is made up of many sub-species, known as subtypes. Depending on the subtype (ST) of Blastocystis that is present in a person, it can lead to a healthy gut in some individuals, and gut problems in others. In Singapore, a rare subtype, Blastocystis ST7, is commonly found in patients with diarrhea. Blastocystis ST7 is more common in Asia than in the West. This observation, along with other supporting studies, suggests that Blastocystis ST7 causes gut disease in humans. However, the detailed way it causes disease, has been a mystery. To find out how Blastocystis ST7 causes gut disease, a team of researchers led by Professor Nicholas Gascoigne, Department of Microbiology and Immunology at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), and Associate Professor Kevin Tan, from the same department, investigated the biology of Blastocystis ST7 at the molecular level. This work is published in The EMBO Journal. The study conducted by Dr Lukasz Wojciech, first author of the paper and Senior Research Fellow from the Department of Microbiology and Immunology at NUS Medicine, revealed that gut disease is caused by Blastocystis ST7, which synthesises a substance during its metabolism, called indole-3-acetyldehyde (I3AA). "I3AA is produced in very few organisms. It binds to immune cells in the gut, which reduces the gut's tolerance for gut bacteria, causing the immune system to flare up even when exposed to normal gut bacteria. I3AA also promotes gut inflammation by inhibiting the protective properties of an important class of immune cells (regulatory T cells), while stimulating inflammation through another class of immune cells (T helper 17 cells) in the gut," said Dr Wojciech. "From a biological perspective, this is the first time that a rare metabolite, I3AA, has been studied in detail, and is shown to promote inflammation," said A/Prof Tan. The researchers also found that some bacteria are useful in negating the effects of I3AA in the gut. One of them is a probiotic group known as lactobacillus -- commonly found in foods like yoghurt, cottage cheese, sourdough bread, and more. It is able to regulate immunity and aid with gastrointestinal diseases. Thus, a way to potentially cure patients from Blastocystis ST7-associated diarrhea, could therefore be to supplement one's diet with foods that contain lactobacilli. "Based on our findings, it is important to identify the specific subtypes involved in Blastocystis-related diseases, as some subtypes are harmful, while others are not. This can potentially result in clearer and more accurate diagnosis and treatment for patients. Our team is currently working on further studies on this. We will be investigating if I3AA production is unique to ST7 and can be used as a biomarker of disease. We are also exploring if certain strains on lactobacilli are able to prevent Blastocystis ST7 inflammatory effects on the host," said Prof Gascoigne.

New research suggests that RNA exosomes -- the cellular machines that degrade old molecules of RNA -- play a key role in the development of B cells, which are critical to the immune system's ability to protect against infection. The findings explain why patients with rare mutations in a gene that codes for this machinery are often immunodeficient and could offer new approaches to treat autoimmune diseases. New research from UT Southwestern suggests that RNA exosomes -- the cellular machines that degrade old molecules of RNA -- play a key role in the development of B cells, which are critical to the immune system's ability to protect against infection. The findings, published in Science Immunology, explain why patients with rare mutations in a gene that codes for this machinery are often immunodeficient and could offer new approaches to treat autoimmune diseases. "It was quite a surprise for us to find that this gene, whose role was well known as part of a disposal system for RNA, is also critical for a very important part of our immune system," said study leader Nan Yan, Ph.D., Professor of Immunology and Microbiology at UT Southwestern and a member of the Harold C. Simmons Comprehensive Cancer Center. Many patients with a rare disease tied to RNA exosome deficiency, known as trichohepatoenteric syndrome (THES), also develop B-cell immunodeficiency and experience recurrent infections. Although researchers have long known that THES is associated with mutations in exosome-encoding genes known as SKIV2L and TTC37, the molecular basis of the disease has been unknown. To better understand the role of SKIV2L in THES, Dr. Yan's research team in the Department of Immunology and colleagues at the Primary Immunodeficiency Clinic at UTSW and Children's Medical Center Dallas studied a THES patient who carried this mutation and was part of a clinical research study led by Christian Wysocki, M.D., Ph.D., Associate Professor of Pediatrics. In addition to the usual clinical features of THES, a multi-organ disorder with symptoms including small size at birth, intractable diarrhea, distinctive "wooly" hair, and liver diseases, this patient had a severely low blood count of B cells. Researchers then generated mice whose SKIV2L gene had been deleted in bone marrow stem cells that generate B cells. The animals also had B-cell deficiencies; further research showed that the B cells never matured because a key part of their development -- in which progenitor cells randomly recombine genetic material to create a diverse B-cell pool -- did not occur. Dr. Yan explained that this appears to be related to SKIV2L's role in RNA degradation. In a separate finding published in the same issue of Science Immunology, researchers at Columbia University showed mutations in other components of the RNA exosome also cause B-cell deficiency. These mutations render RNA exosomes nonfunctional, causing cells to selectively retain RNA, particularly the non-coding form that doesn't produce proteins. When B-cell progenitors become gunked up with excessive non-coding RNA, they can't mature into functional B cells. Taken together, the findings suggest that THES might be treated with a bone marrow transplant, replacing faulty B-cell progenitors that carry a genetic mutation with healthy ones. They also suggest that SKIV2L could offer a new target for fighting autoimmune diseases such as lupus, in which overactive B cells play a key role. By inhibiting the activity of this gene, Dr. Yan explained, it may be possible to control the number of B cells, lowering the intensity of autoimmune attack. Dr. Yan is the Rita C. and William P. Clements, Jr. Scholar in Medical Research. Other UTSW researchers who contributed to this study include Kun Yang (first author), Jie Han, Jennifer G. Gill, Jason Y. Park, Meghana N. Sathe, Jyothsna Gattineni, and Tracey Wright. M. Teresa de la Morena of the University of Washington also contributed. This research was supported by grants from the National Institutes of Health (AI153576) and the Burroughs Wellcome Fund.

Merger of Napo EU and Dragon SPAC targeted for mid-2021 Jaguar kicks off educational awareness contest in honor of HIV Long-Term Survivors Awareness Day and the 40th anniversary of the first publication defining HIV SAN FRANCISCO, CA / ACCESSWIRE / April 15, 2021 / Jaguar Health Inc. (NASDAQ:JAGX) ("Jaguar" or the "Company"), today announced the upsizing by $15.3 million of the at-the-market ("ATM") financing program the Company established on October 5, 2020 with Ladenburg Thalmann & Co. Inc. ("Ladenburg") for potential future financing needs. On April 9, 2021, the Company filed a registration statement and prospectus supplement in connection with its previously disclosed At The Market Offering Agreement with Ladenburg, as agent, to increase the size of the at-the-market offering pursuant to which the Company may offer and sell, from time to time through Ladenburg, shares (the "ATM Shares") of the Company's common stock. "We are very pleased to have expanded the capacity of the ATM program," said Lisa Conte, Jaguar's president and CEO. "While we do not anticipate issuing any shares at this time, the upsized ATM program is available to provide the Company with future funding, if needed, at the prevailing market price at the time of sale, hence, based on timing, potentially priced at-the-market, or above-the-market, as defined by Nasdaq." "Jaguar and Napo Pharmaceuticals, our wholly owned subsidiary, have multiple clinical programs that are funded with non-dilutive financing," Conte said, "including Napo's ongoing pivotal Phase 3 trial of crofelemer for prophylaxis of diarrhea in adult cancer patients receiving targeted therapy ("cancer therapy‑related diarrhea" ("CTD")), and our planned development program for lechlemer for the indication of the symptomatic relief of diarrhea and dehydration in cholera patients. On the financing front, it is important for the Company to have the flexibility to respond to relevant and critical emerging clinical needs as well - such as COVID-related diarrhea." As announced, the Company is actively pursuing conditional marketing authorization from the European Medicines Agency for crofelemer for COVID-related diarrhea through Napo EU S.p.A. ("Napo EU"), Jaguar's wholly owned Italian subsidiary. "We expect that clinical efforts related to COVID-related diarrhea will be funded by the anticipated merger - aimed for mid-2021 - of Napo EU with the Dragon special purpose acquisition company (the "Dragon SPAC"), which is anticipated to be listed on AIM Italia," Conte added. Jaguar Kicks Off Educational Awareness Contest in Honor of HIV Long-Term Survivors Awareness Day and the 40th anniversary of the First Publication Defining HIV In honor of HIV Long-Term Survivors Awareness Day and the 40th anniversary of the first publication defining HIV (both dates fall on June 5, 2021), and the great level of participation in Jaguar's International Day of Forests Contest last month, Jaguar is conducting an educational awareness contest to raffle off a second signed print of the original painting of a Jaguar by Anthony J. Conte. The painting was inspired by a photograph of a Jaguar taken by Christopher Scharf in the Cockscomb Basin Wildlife Sanctuary & Jaguar Preserve in Belize. The winner will be chosen at random from the pool of contest participants who correctly answer all or most questions in the multiple-choice entry form. Entries must be received by 9:00 a.m. US Eastern Time on June 4, 2021. No fee is required to enter the contest. Additional contest terms and conditions apply. Click here to enter and for contest terms and conditions. "Given the enthusiastic response last month to Jaguar's first educational awareness contest, we've launched a second contest with the prize being another signed and framed print (2/25) of this original painting of a jaguar by Anthony J. Conte," said Conte. "I am also pleased to announce that we've launched a new Instagram account to serve as the central communication hub for community-building activities of this kind. Please click here to visit the new ‘Jaguar Health Community' page on Instagram, and please click ‘Follow' on the account so that you learn about our future educational events and activities related to rainforests, the history of plant-based medicines, and other topics of interest." Anthony J. Conte, 90, is an accomplished painter, published journalist, a lifelong outdoor enthusiast, and an accomplished figure skater who began skating at the age of 67. His oil paintings have been auctioned at fundraising events for conservation groups such as the Atlantic Salmon Federation and Wild Sheep Foundation. "Eye, Jaguar" is his first painting of a rainforest-dwelling mammal, created for and gifted to Jaguar Health, Inc. To learn more about HIV Long-Term Survivors Awareness Day, click here . To read about the first publication defining HIV, click here to visit the related blog entry on the U.S. Department of Health & Human Services' HIV.gov website. This press release shall not constitute an offer to sell or a solicitation of an offer to buy any ATM Shares, nor shall there be any sale of such ATM Shares in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction. About Jaguar Health, Inc. and Napo Pharmaceuticals, Inc. Jaguar Health, Inc. is a commercial stage pharmaceuticals company focused on developing novel, plant-based, non-opioid, and sustainably derived prescription medicines for people and animals with GI distress, specifically chronic, debilitating diarrhea. Our wholly owned subsidiary, Napo Pharmaceuticals, Inc., focuses on developing and commercializing proprietary plant-based human gastrointestinal pharmaceuticals from plants harvested responsibly from rainforest areas. Our Mytesi® (crofelemer) product is approved by the U.S. FDA for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy and the only oral plant-based prescription medicine approved under FDA Botanical Guidance. For more information about Jaguar, please visit . For more information about Napo, visit . About Mytesi® Mytesi® (crofelemer delayed release tablets) is an antidiarrheal indicated for the symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy (ART). Mytesi® is not indicated for the treatment of infectious diarrhea. Rule out infectious etiologies of diarrhea before starting Mytesi®. If infectious etiologies are not considered, there is a risk that patients with infectious etiologies will not receive the appropriate therapy and their disease may worsen. In clinical studies, the most common adverse reactions occurring at a rate greater than placebo were upper respiratory tract infection (5.7%), bronchitis (3.9%), cough (3.5%), flatulence (3.1%), and increased bilirubin (3.1%). More information and complete Prescribing Information are available at Mytesi.com. Crofelemer, the active ingredient in Mytesi®, is a botanical (plant-based) drug extracted and purified from the red bark sap of the medicinal Croton lechleri tree in the Amazon Rainforest. Napo has established a sustainable harvesting program for crofelemer to ensure a high degree of quality and ecological integrity. Forward-Looking Statements Certain statements in this press release constitute "forward-looking statements." These include statements regarding the Company's expectation that the merger of Napo EU and the Dragon SPAC may occur in mid-2021, and the Company's expectation that clinical efforts related to COVID-related diarrhea will be funded by the anticipated merger. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intend," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or other similar expressions. The forward-looking statements in this release are only predictions. Jaguar has based these forward-looking statements largely on its current expectations and projections about future events. These forward-looking statements speak only as of the date of this release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Jaguar's control. Except as required by applicable law, Jaguar does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact: Peter Hodge Jaguar Health, Inc. phodge@jaguar.health Jaguar-JAGX SOURCE: Jaguar Health, Inc. View source version on accesswire.com: