Tooth Fractures

PHILADELPHIA, June 11, 2024 /PRNewswire/ -- As humans age, hematopoietic stem cells—the immature precursor cells that give rise to all blood and immune cells—accumulate mutations. Some of the mutations allow these stem cells to self-renew and expand more effectively than their non-mutated counterparts. This relatively poorly understood condition, known as clonal hematopoiesis of indeterminate potential (CHIP), is detectable in more than 10% of people older than 65 and is linked to increased risks of various inflammation-related diseases. "These mutations change the character of the progeny cells, making them more inflammatory," says Dr. George Hajishengallis of Penn Dental Medicine. "When a large fraction of your immune cells are derived from these mutant stem cells, it spells bad news for chronic inflammatory diseases." Now, a team led by Hajishengallis, together with collaborators at the Dresden University of Technology and the University of North Carolina at Chapel Hill (UNC), have uncovered mechanistic insights into CHIP. They also found that an FDA-approved drug for preventing organ transplant rejection, rapamycin, has the potential to block these mutant stem cells and treat CHIP-driven inflammatory bone loss diseases, such as periodontitis and arthritis. Their research is published in the journal Cell. "We found a compelling observational association between DNMT3A, a gene most commonly affected in CHIP, and the prevalence and severity of periodontitis in a cohort of 4,946 people aged 52 to 74," Hajishengallis says. "What's more, we corroborated these findings with our mouse model, demonstrating a strong causal relationship between DNMT3A mutations and increased susceptibility to inflammatory bone loss disorders. And most excitingly, we were able to show the efficacy of rapamycin in protecting mice from CHIP-exacerbated inflammatory bone loss, which paves the way for eventually treating such diseases in humans." Considering potential therapeutic strategies Hajishengallis says, "Screening for CHIP among the elderly population may identify individuals with increased risk for inflammatory comorbidities." These individuals may benefit from therapeutic interventions aiming to block the aberrant expansion of the CHIP-mutant hematopoietic stem cell clones and their adverse impact on chronic inflammatory comorbidities. Read more on the study >> CONTACT: Beth Adams, [email protected] SOURCE PENN DENTAL MEDICINE

Ansel changed its name from Brella Insurance this year. Its new name translates to “protector” in German, alluding to the company’s commitment of shielding its members from financial implications of medical events. An insurtech has raised $20 million through a funding round led by VC group Portage. Ansel, a company that offers simplified supplemental insurance for members diagnosed with more than 13,000 conditions, has now raised more than $50 million in total, according to a press release. The company's mission is to enhance, but not coordinate with, primary health insurance to help individuals with rising medical bills. Ansel was previously known as Brella Insurance. Members receive varying levels of cash payouts that depend on the condition, which are rated either moderate, severe or catastrophic. Moderate conditions include concussions, cracked teeth, fractures and ACL sprains, while appendicitis, endocarditis and pulmonary embolisms would be classified as severe conditions. Ansel's website lists cancer, cardiac arrest, ALS, heart attacks, Parkinson's and strokes as examples of the more than 1,500 catastrophic conditions covered. Pre-existing conditions are also covered. The company will use the latest investments to scale its insurance offerings to employees across the country, including the 11 states Ansel is not yet available. “Since launching Ansel in 2019, we’ve made significant progress bringing modern supplemental insurance to more Americans by teaming up with leading insurance carriers and benefits brokerage firms across the country,” said founder and CEO Veer Gidwaney in a statement. “This financing is an important step towards making health hardships less of a financial burden for Americans nationwide.” Ansel highlighted its high net promoter score of 90 in 2023 in its latest announcement, attributing the rating to its new claims automation service that allows members to receive benefits without filing a claim. Ricky Lai, a partner at Portage, in a statement said he finds confidence with Ansel's approach because of nationwide growth in high-deductible health plans. Other groups participating in funding included Two Sigma Ventures, Brewer Lane Ventures and Morgan Creek Capital Management.

Image courtesy of Getty Images TenSixteen Bio recently came out of stealth mode with $40 million in funding to target somatic mosaicism – particularly clonal hematopoiesis of indeterminate potential (CHIP). TenSixteen Bio recently came out of stealth mode with $40 million in funding to target somatic mosaicism – particularly clonal hematopoiesis of indeterminate potential (CHIP). Its approach is based upon leveraging the growing body of knowledge of somatic mosaicism variations to develop insights into better-designed therapies or stratify disease risks for a plethora of diseases. Somatic mosaicism occurs from postzygotic mutations and results in two genetically distinct cell populations within an individual. CHIP is a subset of that. It appears in the blood and is caused by mutations in a set of cancer-associated genes. CHIP is an extremely broad, generally unacknowledged disease essential for blood cancers, autoimmune disease, infections and other conditions. It even increases susceptibility to COVID-19. CHIP is thought to affect 10% of the population over age 70. Though most patients don’t know they have CHIP, the risk of having mutations that lead to blood cancer is less than 1%. Despite this seemingly small risk, “CHIP has the potential of affecting all of us,” Mark Chao, M.D., Ph.D., CEO and co-founder of TenSixteen Bio, told BioSpace. “As we age, we develop mutations in the CHIP genes associated with cancer. Some individuals with CHIP have a 10- to 50-fold higher risk of developing cancer or experiencing heart attacks, yet nobody has developed a therapeutic for CHIP. Now, however, we’re seeing increasing momentum and actionable results from studies. Important papers are being published about CHIP nearly weekly.” While Chao joked that he seems to have a penchant for naming companies after numbers – he co-founded Forty Seven , which Gilead Sciences acquired for $4.9 billion – the name is tightly linked to the company’s scientific foundation. “1016 is the estimated number of times a cell divides in a human body’s lifetime,” Chao explained. “That gets to the idea of somatic mosaicism. Each time a cell divides, there’s an opportunity to mutate.” TenSixteen aims to treat diseases arising from CHIP early, when there are few mutations, so disease escalation can be prevented or at least minimized. Ideally, he said, patients could be treated for CHIP to address the underlying cause of disease and then with precision medicine therapies. There’s also a second approach that involves a screening program to detect CHIP mutations. TenSixteen is developing a diagnostic, chip-based sequencing assay for research settings. Chao said this has the potential to be “paradigm-changing, like adjuvant therapy for breast cancer, which revolutionized that field.” With the company just uncloaking in late January, it’s too early to reveal potential targets. Chao said, though, that “Some will be novel, and others will involve drugs we can repurpose for the CHIP population. There’s a lot of variety and flexibility in terms of how we think about drug development.” TenSixteen’s immediate goal is to build out its infrastructure and management and scientific teams, as well as to identify and prosecute new targets. “We’re building an extensive data and multiomics platform that will provide access to several hundreds of thousands of patients. That will enable us to discover new targets for CHIP as well as to identify which patients are at risk of developing further diseases and which will likely respond to treatment,” Chao said. The company was incubated by Foresite Labs , which accelerates company growth by applying significant computational expertise to the challenge. By developing comprehensive databases followed by artificial intelligence and machine learning algorithms, its companies have a track record of achieving meaningful insights quickly, thus noticeably shortening the scaleup and development timelines. “It was really important to find the right partners,” Chao said. “I talked with Foresite for nine months, and they had thought about the concept (of somatic mosaicism and CHIP) for two years. Developing insights in CHIP requires the expertise in large-scale data and analytics that Foresite has. It allows us a fast start and to leverage expertise.” Foresite Labs and GV (formerly known as Google Ventures) provided the initial $40 million funding. “The team, founders and investors are really excited about this space. The potential to treat patients early with novel, impactful biology is truly exciting,” Chao said.