How to Prevent Tooth Loss

Research headed by scientists at the National Institute of Dental and Craniofacial Research (NIDCR) has shown how blocking the function of the blood clotting protein, fibrin, prevents bone loss from periodontal (gum) disease in mice. Drawing on animal and human data, the study—headed by NIDCR investigators Niki Moutsopoulos, DDS, PhD, and Thomas Bugge, PhD, found that build-up of fibrin triggers an overactive immune response that damages the gums and underlying bone. The results suggest that suppressing abnormal fibrin activity could hold promise for preventing or treating periodontal disease, as well as other inflammatory disorders—including arthritis and multiple sclerosis—that are marked by fibrin buildup.

Severe periodontal disease can lead to tooth loss and remains a barrier to productivity and quality of life for far too many Americans, especially those lacking adequate access to dental care,” said NIDCR director Rena D’Souza, DDS, PhD. “By providing the most comprehensive picture yet of the underlying mechanisms of periodontal disease, this study brings us closer to more effective methods for prevention and treatment.”

Periodontal disease is a bacterial infection of the tissues supporting the teeth. The condition affects nearly half of people in the United States who are over the age 30, and 70% of those who are 65 years and older. In its early stages, periodontal disease causes redness and swelling (inflammation) of the gums. In advanced stages, called periodontitis, the underlying bone becomes damaged, leading to tooth loss. While scientists have known that periodontitis is driven in part by an exaggerated immune cell response, until now, it was unclear what triggered the response, and how it caused tissue and bone damage.

Moutsopoulos, Bugge, and colleagues reported their findings in Science, in a paper titled, “Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier.”

 

Source: https://www.genengnews.com/

Two New Trials of Coronavirus Treatment

Drugs used for treating arthritis are being tested as treatments for COVID-19, the disease caused by a new coronavirus, as researchers rush to find ways of helping patients and slowing the number of infectionsSanofi and Regeneron Pharmaceuticals said on Monday they began a clinical trial of their rheumatoid arthritis drug Kevzara as a coronavirus treatment, while in Spain a separate trial is studying if a combination of two drugs can slow down the spread of coronavirus among people. Enrolments for the mid-to-late stage trial of Kevzara, an immune-system modifying drug known as a monoclonal antibody, will begin immediately and test up to 400 patients, Sanofi and Regeneron said in a joint statement. Regeneron in February announced a partnership with the U.S. Department of Health and Human Services to develop a treatment for the new coronavirus, called SARS-CoV2, and said it would focus on monoclonal antibodies.

The virus that emerged in central China in December has now infected more than 179,000 people worldwide, according to the Johns Hopkins University, which is tracking these figures. Doctors have seen that many of those who become critically ill from SARS-CoV2 are experiencing a so-called cytokine storm, which happens when the immune system overreacts and attacks the body’s organs. Some researchers think drugs that can suppress the immune system, including monoclonal antibodies, might be useful for limiting this autoimmune response.

Meanwhile, Barcelona-based researchers said on Monday they would administer a drug used to treat HIV – containing darunavir and cobicistat – to a coronavirusinfected person. The patient’s close contacts would be administered hydroxychloroquine, a drug for malaria and rheumatoid conditions because laboratory experiments suggest it prevents this strain of coronavirus from reproducing. “The goal of our study is to separate the transmission chains,” Oriol Mitja, researcher at Germans Trias i Pujol Research Institute, told a news briefing. Patients with coronavirus can infect between 5% and 15% of the people they come into contact with during the 14 days after starting to show symptoms, he said. The trial’s goal is to reduce that number below 14 days and also to reduce the percentage of contacts infected and researchers plan to analyze the results in 21 days. Around 200 patients with coronavirus and 3,000 of their close contacts will take part in the trial, which has private and public funding.

Source: https://www.reuters.com/

New Cause Of Cell Aging Discovered: Findings Have Huge Implications

New research from the USC Viterbi School of Engineering could be key to our understanding of how the aging process works. The findings potentially pave the way for better cancer treatments and revolutionary new drugs that could vastly improve human health in the twilight years. The work, from Assistant Professor of Chemical Engineering and Materials Science Nick Graham and his team in collaboration with Scott Fraser, Provost Professor of Biological Sciences and Biomedical Engineering, and Pin Wang, Zohrab A. Kaprielian Fellow in Engineering, was recently published in the Journal of Biological Chemistry.

LEFT: NON-SENESCENT CELLS WERE SHOWN WITH DIFFERENT COLORS. RIGHT: SENESCENT CELLS APPEARED OFTEN WITH MULTIPLE BLUE NUCLEI AND DID NOT SYNTHESIZE DNA.

To drink from the fountain of youth, you have to figure out where the fountain of youth is, and understand what the fountain of youth is doing,” Graham said. “We’re doing the opposite; we’re trying to study the reasons cells age, so that we might be able to design treatments for better aging.”

To achieve this, lead author Alireza Delfarah, a graduate student in the Graham lab, focused on senescence, a natural process in which cells permanently stop creating new cells. This process is one of the key causes of age-related decline, manifesting in diseases such as arthritis, osteoporosis and heart disease.

Senescent cells are effectively the opposite of stem cells, which have an unlimited potential for self-renewal or division,” Delfarah said. “Senescent cells can never divide again. It’s an irreversible state of cell cycle arrest.”

The research team discovered that the aging, senescent cells stopped producing a class of chemicals called nucleotides, which are the building blocks of DNA. When they took young cells and forced them to stop producing nucleotides, they became senescent, or aged. “This means that the production of nucleotides is essential to keep cells young,” Delfarah said. “It also means that if we could prevent cells from losing nucleotide synthesis, the cells might age more slowly.”

Graham’s team examined young cells that were proliferating robustly and fed them molecules labeled with stable isotopes of carbon, in order to trace how the nutrients consumed by a cell were processed into different biochemical pathways.

Scott Fraser and his lab worked with the research team to develop 3D imagery of the results. The images unexpectedly revealed that senescent cells often have two nuclei, and that they do not synthesize DNA. Before now, senescence has primarily been studied in cells known as fibroblasts, the most common cells that comprised the connective tissue in animals. Graham’s team is instead focusing on how senescence occurs in epithelial cells, the cells that line the surfaces of the organs and structures in the body and the type of cells in which most cancers arise. Graham said that senescence is most widely known as the body’s protective barrier against cancer: When cells sustain damage that could be at risk of developing into cancer, they enter into senescence and stop proliferating so that the cancer does not develop and spread.

Sometimes people talk about senescence as a double-edged sword, that it protects against cancer, and that’s a good thing,” Graham said. “But then it also promotes aging and diseases like diabetes, cardiac dysfunction or atherosclerosis and general tissue dysfunction,” he said. Graham said the goal was not to completely prevent senescence, because that might unleash cancer cells. “But then on the other hand, we would like to find a way to remove senescent cells to promote healthy aging and better function,” he explained.

Graham underscores that the team’s research has applications in the emerging field of senolytics, the development of drugs that may be able to eliminate aging cells. He said that human clinical trials are still in early stages, but studies with mice have shown that by eliminating senescent cells, mice age better, with a more productive life span. “They can take a mouse that’s aging and diminishing in function, treat it with senolytic drugs to eliminate the senescent cells, and the mouse is rejuvenated. If anything, it’s these senolytic drugs that are the fountain of youth,” Graham said. He added that in order for successful senolytic drugs to be designed, it was important to identify what is unique about senescent cells, so that drugs won’t affect the normal, non-senescent cells.

That’s where we’re coming in–studying senescent cell metabolism and trying to figure out how the senescent cells are unique, so that you could design targeted therapeutics around these metabolic pathways,” Graham added.

Source: https://viterbischool.usc.edu/
AND
https://eurekalert.org/

Remote-Controlled Drug Delivery Implant

People with chronic diseases like arthritis, diabetes and heart disease may one day forego the daily regimen of pills and, instead, receive a scheduled dosage of medication through a grape-sized implant that is remotely controlled.

Researchers from Houston Methodist successfully delivered continuous, predetermined dosages of two chronic disease medications using a nanochannel delivery system (nDS) that they remotely controlled using Bluetooth technology. The nDS device provides controlled release of drugs without the use of pumps, valves or a power supply for possibly up to year without a refill for some patients. This technology will be tested in space next year.

A proof-of-concept paper recently published in Lab on a Chip (online June 25) explains how the Houston Methodist nanomedicine researchers accomplished long-term delivery of drugs for rheumatoid arthritis and high blood pressure, medications that are often administered at specific times of the day or at varying dosages based on patient needs.

Nanomedicine scientists at Houston Methodist Research Institute created a remote-controlled implantable nanochannel drug delivery system (nDS) the size of a grape

We see this universal drug implant as part of the future of health care innovation. Some chronic disease drugs have the greatest benefit of delivery during overnight hours when it’s inconvenient for patients to take oral medication. This device could vastly improve their disease management and prevent them from missing doses, simply with a medical professional overseeing their treatment remotely,” said Alessandro Grattoni, Ph.D., corresponding author and chair of the department of nanomedicine at Houston Methodist Research Institute.

Grattoni and the Houston Methodist researchers have worked on implantable nanochannel delivery systems to regulate the delivery of a variety of therapies for medical issues ranging from HIV-prevention to cancer. As basic research progresses with the remote-controlled device, the Houston Methodist technology is planned for extreme remote communication testing on the International Space Station in 2020. The team hopes that one day the system will be widely available to clinicians to treat patients remotely via telemedicine. This could provide both an improvement in the patients’ quality of life and a reduction of cost to the health care system.

Source: https://www.houstonmethodist.org/

How To Heal Arthritis

Osteoarthritis, a disease that causes severe joint pain, affects more than 20 million people in the United States. Some drug treatments can help alleviate the pain, but there are no treatments that can reverse or slow the cartilage breakdown associated with the disease.

In an advance that could improve the treatment options available for osteoarthritis, MIT engineers have designed a new material that can administer drugs directly to the cartilage. The material can penetrate deep into the cartilage, delivering drugs that could potentially heal damaged tissue.

Six days after treatment with IGF-1 carried by dendrimer nanoparticles (blue), the particles have penetrated through the cartilage of the knee joint.

This is a way to get directly to the cells that are experiencing the damage, and introduce different kinds of therapeutics that might change their behavior,” says Paula Hammond, head of MIT’s Department of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the study. Treating  rats, the researchers showed that delivering an experimental drug called insulin-like growth factor 1 (IGF-1) with this new material prevented cartilage breakdown much more effectively than injecting the drug into the joint on its own.

Brett Geiger, an MIT graduate student, is the lead author of the paper, which appears in Science Translational Medicine.

Source: http://news.mit.edu/

CRISPR-SKIP, New Gene Editing Technique

What if doctors could treat previously incurable genetic diseases caused by errors or mutations in genes? Thanks to new research by American scientists at the University of Illinois, we are one step closer to making that a reality. Published in Genome Biology, their work is based on CRISPR-Cas9, a groundbreaking genome editing system.

Typically, cells in the body “readDNA to produce the proteins needed for different biological functions. . Scientists can change how the DNA is read using CRISPR gene-editing technology. CRISPR-Cas9 is often used to cut out specific areas of DNA and repair faulty genes. In the current study, the researchers modified existing technology to create CRISPR-SKIP. Instead of breaking DNA to cut faulty genes out, CRISPR-SKIP changes a single base of the targeted DNA sequence, causing the cell to skip reading that section of DNA.

According to the study authors, CRISPR-SKIP can eliminate faulty sections of DNA permanently, allowing for long-lasting treatment of some genetic diseases with one treatment. They successfully tested their technique in cell lines from both mice and humans. The scientists aim to test the method in live organisms in the future.

CRISPR-SKIP has the potential to help treat many diseases such as cancer, rheumatoid arthritis, Huntington’s disease, and Duchenne muscular dystrophy to name a few. Because the method only requires editing of a single base, it is simple, precise, and adaptable to a variety of cell types and applications.

Source: https://news.illinois.edu/
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https://www.medicalnewsbulletin.com/