For the first time, scientists at the University of North Carolina at Chapel Hill (UNC-Chapel Hill) have packaged the cancer drug paclitaxel into exosomes — membrane-bounded vesicles derived from a patient’s own immune system — and thus made the drug 50 times more potent against mulit-drug-resistant (MDR) lung-cancer tumors. Elena Batrakova (photo) (https://pharmacy.unc.edu/directory/batrakov/), Ph.D., and her colleagues at the UNC Eshelman School of Pharmacy’s Center for Nanotechnology in Drug Delivery (CNDD) harvested exosomes from macrophages, phagocytic white blood cells that help protect the body against infection. Exosomes frequently carry chemical messages and are bound by the same material found in cell membranes. It is now believed that diseases like cancer and AIDS may propagate throughout the body, in part, by hijacking exosomes, but Dr. Batrakova is using these vesicles as a natural drug-delivery system. The exosomes can also deliver a dye that stains tumor cells and makes it easy to see how widespread a particular cancer is. Like the synthetic nanoparticles currently being used to deliver many chemotherapeutic agents, exosomes have a natural ability to home in on tumors. Unlike those man-made particles, however, which are often seen as foreign objects and swept up by the immune system, exosomes derived from white blood cells are ignored by the patient’s natural defenses because they are part of that defense system and they are allowed to deliver their payload unimpeded. The UNC team’s findings were published online on November 13, 2015 in Nanomedicine: Nanotechnology, Biology and Medicine. The article is titled “Development of Exosome-Encapsulated Paclitaxel to Overcome MDR in Cancer Cells.” “Exosomes are engineered by nature to be the perfect delivery vehicles,” said Dr.
Data measured using the NanoSight NS300 (http://www.malvern.com/en/products/product-range/nanosight-range/nanosig...) from Malvern Instruments is providing new insights into the role of exosomes in diseases such as cancer, arthritis, Alzheimer’s disease, and cystic fibrosis, in pioneering research being carried out at the University of Alabama--Birmingham (UAB). On January 27, 2016, Malvern published a press release describing the experiences that those using the NanoSight NS300 at UAB are having. “Early research on exosomes, or extracellular vesicles (ECVs), focused on their role in excreting unwanted waste from cells,” said Shawn Williams, facility manager and imaging specialist at UAB “However, we’re now starting to understand their wider functionality in intercellular communication and the transmission of disease. The NanoSight system is playing a central role in helping us advance in this new and exciting area of research, by enabling us to size, count and track the movement of these crucial molecules in their native state.” The NanoSight NS300 system is sited within an analytical service facility for the university, which also extends support to external customers on a contract basis. Approximately 85% of the analysis being carried out in the lab at UAB is associated with disease-related research. The NanoSight system is used by several hundred different researchers, so rapid training and robust measurement protocols are essential. Mr. Williams and his team have developed a series of simple procedures to support new researchers in their use of the instrument, to enable the efficient generation of accurate particle size and count data, and video footage of the exosomes within a sample.
Researchers in China have shown that immunizing heart-allograft-recipient mice with donor-derived peripheral exosomes, inhibits the donor antigen-specific T helper 2 (Th2)-pattern inflammation normally observed in the allograft hearts and prolongs allograft survival. In the study, peripheral exosomes were purified from the mouse serum. A heart transplantation mouse model was developed. The immune inflammation of the allograft heart was assessed by histology and flow cytometry. The results showed that donor-antigen-specific Th2-pattern inflammation was observed in the allograft hearts; the inflammation was inhibited by immunizing the recipient mice with the donor-derived exosomes. Purified peripheral exosomes contained integrin MMP1; the latter induced CD4+ T cells to express Forkhead protein-3 and transforming growth factor (TGF)-β via inhibiting the Th2 transcription factor, GATA binding protein 3, in CD4+ T cells. Administration of the donor-derived exosomes significantly prolonged the allograft heart survival. The authors concluded that the donor-derived peripheral exosomes have the capacity to inhibit the immune inflammation in the allograft heart via inducing specific Treg cells, implying that administration with the donor-derived exosomes may be beneficial to cardiac transplantation. This work is described in an open-access article published online on January 29, 2016 in Scientific Reports. The article is titled “Donor-Derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart. The work was carried out by researchers at the State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College.
On January 11, 2016, the ReNeuron Group plc (AIM: RENE), a leading UK-based stem cell therapy development company, announced that it has been awarded a £2.1 million (just over $3 million) grant from Innovate UK to further advance the company’s emerging exosome nanomedicine platform (http://www.reneuron.com/products/ctx-derived-exosomes/). The grant, entitled “Stem Cell-Derived Exosomes for Regenerative Medicine,” has been awarded under Innovate UK’s Developing Regenerative Medicine & Cell Therapies” grant scheme and will fund a collaborative program of work to be undertaken by ReNeuron, as lead participant, and its collaborators on the grant, namely, the Cell Therapy Catapult and the Department of Biochemical Engineering at University College London. The grant will fund key pre-clinical development work packages relating to ReNeuron’s exosome nanomedicine platform. These include the development of robust manufacturing systems utilizing scalable bioreactors and purification technologies that will enable the production of ReNeuron’s exosomes at a commercial scale. The work program also includes product characterization and potency assay development, as well as pre-clinical efficacy and toxicity testing of the selected exosome nanomedicine candidate. ReNeuron is exploiting the therapeutic potential of exosomes derived from its proprietary stem cell lines. The company is also exploring the potential of its exosomes as a delivery system for gene therapy treatments. Exosomes are lipid-based nanoparticles secreted from all cells and which are believed to play a key role in the transfer of beneficial proteins and particularly non-coding RNAs from one cell to another.
Fetal development has been known to play an important role in social interaction, a fundamental behavior found in nearly all organisms, and later adult social behaviors. Autism, a highly heritable neurodevelopment disorder that causes difficulties with social interactions, has been postulated to be caused by neuron overgrowth in the prenatal period, although the precise timing and cause of this overgrowth has been unknown. Recently, researchers at the Case Western Reserve University School of Medicine, the University of California at San Francisco (UCSF) School of Medicine, and other institutions have uncovered abnormalities in embryonic brain development in mice, including transient embryonic brain enlargement during neuron formation, that are responsible for abnormal adult brain structures and behavioral abnormalities in adult mice. These findings demonstrate a fetal origin for social and repetitive behavior deficits, as seen in disorders such as autism. Using engineered mice, the researchers identified a critical period during embryonic brain development for the establishment of normal social behavior and they were able to link this critical period with abnormalities in specific adult brain structures. After identifying these abnormalities, the researchers were then able to intervene and treat mice during fetal development. The embryonically treated mice progressed without adult behavioral deficits. Further studies will be required to determine the consequences of abnormal development of cortical neurons on adult brain circuitry and function, as well as possible therapeutic interventions. The results of the study were published online on February 2, 2014 in Molecular Psychiatry. The article is titled “Prenatal β-catenin/Brn2/Tbr2 Transcriptional Cascade Regulates Adult Social and Stereotypic Behaviors.”
In a report to be presented on Thursday, February 4, 2016, at 1:15 p.m. EST, at the Society for Maternal-Fetal Medicine's (SMFM’s) annual meeting, The Pregnancy Meeting™, in Atlanta, Georgia, researchers from Canada will present findings from a study titled, “High-Flavanol Chocolate to Improve Placental Function and to Decrease the Risk of Preeclampsia: A Double-Blind Randomized Clinical Trial.” In light of previous studies showing conflicting results regarding the role of chocolate consumption during pregnancy and the risk of preeclampsia, this study set out to evaluate the impact of high-flavanol chocolate. Researchers conducted a single-center randomized controlled trial of 129 women with singleton pregnancy between 11 and 14 weeks gestation who had double-notching on uterine artery Doppler. The pregnant women selected were randomized to either high-flavanol or low-flavanol chocolate. A total of 30 grams of chocolate was consumed daily for 12 weeks and women were followed until delivery. Uterine artery Doppler pulsatility index was at baseline and 12 weeks after randomization. Preeclampsia, gestational hypertension, placenta weight, and birthweight were also evaluated. The result was that there was no difference in preeclampsia, gestational hypertension, placental weight, or birthweight in the two groups; however, the uterine artery Doppler pulsatility index (a surrogate marker of blood velocity in the uterine, placental and fetal circulations) in both groups showed marked improvement that was much greater than expected in the general population.
Researchers from the Mayo Clinic in Arizona and from the Banner Sun Health Research Institute, also in Arizona, have determined that testing a portion of a person's submandibular gland, which is a gland that makes saliva, may be a way to diagnose early Parkinson's disease. The new study was published online on January 22, 2016 in Movement Disorders, the official journal of the International Parkinson and Movement Disorders Society. The article is titled “Peripheral Synucleinopathy in Early Parkinson's Disease: Submandibular Gland Needle Biopsy Findings.” Currently, there is no accurate diagnostic test for Parkinson's disease. The researchers believe that a procedure termed transcutaneous submandibular gland biopsy may provide the needed accuracy. The test involves inserting a needle into the submandibular gland under the jaw and withdrawing the needle to obtain the core of gland tissue within. The researchers looked for a protein in the cells from patients who have early Parkinson's disease and compared this to subjects without the disease. "This is the first study demonstrating the value of testing a portion of the submandibular gland to diagnose a living person with early Parkinson's disease. Making a better diagnosis in living patients is a big step forward in our effort to understand and better treat patients," says study author Charles Adler, M.D., Ph.D., neurologist, Professor of Neurology, at the Mayo Clinic in Arizona. The study involved 25 patients with Parkinson's disease for less than five years and 10 control subjects without Parkinson's disease. Biopsies were taken from one submandibular gland. The biopsies were done as an office procedure by Michael Hinni, M.D., and David Lott, M.D., at the Mayo Clinic in Arizona.
Exosome Sciences, Inc., in collaboration with majority shareholder Aethlon Medical, Inc. (Nasdaq: AEMD), announced, on January 12, 2016, that it has agreed to participate in a clinical research study to establish methods for detecting and diagnosing chronic traumatic encephalopathy (CTE) during life, as well as examining risk factors for CTE. CTE is a disease of the brain often found in athletes, military veterans, and others with a history of repetitive head impacts. At present, CTE can only be definitively diagnosed through post-mortem examination of brain tissue. The research study will be conducted under a $16 million grant that the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) has awarded to researchers from Boston University, the Cleveland Clinic, Banner Alzheimer's Institute, and Brigham and Women's Hospital in Boston. Overall, the project will involve a group of approximately 50 investigators, representing 17 research institutions. Exosome Sciences has agreed to test an exosomal tau biomarker (TauSome™) that it has been advancing as a blood-based candidate to diagnose CTE. "We are truly grateful that our colleagues at the Boston University CTE Center have expanded our opportunity to validate our Tausome™ biomarker as a candidate to detect and monitor CTE in living individuals," stated Jim Joyce, Executive Chairman at Exosome Sciences and Chairman and CEO of Aethlon Medical. Mr. Joyce played college football for the University of Maryland, and later played briefly in the NFL for the now-Super-Bowl-bound Denver Broncos, before turning to business and biotech.
While world health leaders race to contain the spread of the mosquito-borne Zika virus in the Americas, researchers at the University of Iowa are reminding doctors in the United States to be on the lookout for two other vector-borne and potentially life-threatening diseases that can be passed from mother to child through the placenta. Chagas disease and leishmaniasis are parasitic diseases found in Mexico, Central America, and South America. In addition, leishmaniasis is also found in some parts of Asia, the Middle East, Africa, and southern Europe. Blood-sucking insects are blamed for transmitting both diseases. Now that scientists know the pathogens can also be passed congenitally, global travel and migration have made people in the U.S. vulnerable. The problem is that most American doctors don't think of parasites from far away places when a sick baby arrives in their office. That needs to change, says Christine Petersen, M.D., Associate Professor of Epidemiology at the University of Iowa (UI) College of Public Health and corresponding author of the paper "A Mother's Gift: Congenital Transmission of Trypanosoma and Leishmania Species," which appeared online on January 28, 2016 in in the open-access journal PLOS Pathogens. "Congenital transmission will be the predominant way that kids in the United States get these diseases because we don't have the bug problem," Dr. Petersen says. "So, you might have a child going into heart failure or with an enlarged liver and spleen, and the doctors can't figure out what's going on, and the child is on death's doorstep." Dr.
Olfactory receptors exist not only in the nose, but also in many other parts of the body, including the liver, the prostate, and the intestines. A research group headed by Professor Hanns Hatt from the Ruhr-Universität Bochum in Germany has now demonstrated the presence of olfactory receptors in white blood cells in humans. Together with colleagues from the Essen University Hospital, the Bochum-based group identified the olfactory receptor 2AT4 (OR2AT4) in a cultivated cell line, taken from patients suffering from chronic myelogenous leukemia (CML). The researchers identified the same receptor in white blood cells isolated from blood freshly obtained from patients suffering from acute myeloid leukemia (AML). OR2AT4 is activated by Sandalore, a synthetic odorant with a sandalwood aroma. In leukemia patients, too many immature blood cells form in the spinal marrow. In myeloid leukemia patients, the uncontrolled proliferation is triggered by a certain type of progenitor cells, namely the myeloblasts. The researchers analyzed OR2AT4 in more detail, both in the cultivated cells and in the cells isolated from the blood of patients suffering from AML. If the Sandalore odorant was used to activate the receptor, this effected an inhibition of leukemia cell growth and caused greater numbers of the leukemia cells to die. The researchers, moreover, observed that more red blood cells formed as a result. “This could be a new starting point for the development of leukemia treatment,” says Professor Hatt. “Acute myeloid leukemia in particular is a disease for which specific medication is not, as yet, available.” With his colleagues, Professor Hatt describes the results in the journal Cell Death Discovery.