Profusa, Inc. announced that it received the CE Mark to market its Lumee Oxygen Platform™ for continuous, real-time monitoring of tissue oxygen. The company will initially market the system for monitoring tissue oxygen in the treatment of peripheral artery disease (PAD). With an annual economic burden of more than $74 billion dollars in the United States alone, PAD affects 202 million people worldwide. PAD leads to narrowing of blood vessels and reduced oxygenated blood flow that can result in amputation of an extremity.
Diabetics often have to contend with wounds that heal poorly. Researchers at the Max Planck Institute for Biology of Ageing, the CMMC, the CECAD Excellence Cluster and the Institute of Genetics of the University of Cologne have now gained new insights into the underlying cellular mechanisms. Their findings could lead to the development of new treatment methods.
According to estimates by the International Diabetes Federation (IDF), some six million people in Germany suffer from diabetes mellitus, around 90 percent of whom have the type 2 form. The disease, which is triggered by a disturbance of insulin metabolism, has serious effects on the entire body. One problem these patients face is poor wound healing.
It had previously been assumed that high levels of glucose in the blood damages vessels and neurons and impairs the immune system, thereby accounting for the wound-healing problems. A Cologne-based research group headed by Linda Partridge, Director of the Max Planck Institute for Biology of Ageing, and Maria Leptin, professor at the Institute of Genetics of the University of Cologne, has now presented in a study that slowed insulin metabolism at the wound site directly affects neighbouring cells involved in wound healing.
Investigations of fly skin Parisa Kakanj, the author of the study, examined the skin of larvae of the fruit fly Drosophila melanogaster. These flies serve as models for diabetes, because insulin metabolism has been strongly conserved over the course of evolution, meaning that flies and mammals are very similar in this respect. Using a precision laser, Kakanj removed a cell from the outermost skin layer of fruit fly larvae and then observed what happens in the neighbouring cells live under the microscope.
“Immediately after a skin injury, the neighbouring cells respond by forming an actomyosin cable,” Kakanj explains. The cable consists of proteins that otherwise occur in muscle fibres, where they are responsible for muscular contraction. After an injury, the cable forms a contractile ring around the wound. It then contracts, sealing off the gap caused by the wound. “However, if insulin metabolism is impaired, as in our genetically modified flies, the cable is weaker and forms much later. This results in incomplete or slow wound healing,” as Kakanj relates.
New treatments for impaired wound healing could precisely target this mechanism. “Our findings raise hope of a potential treatment for diabetics. In future, it may be possible to treat wound sites with drugs that locally activate insulin metabolism,” Kakanj explains. The research team is now working closely with Sabine Eming, a senior dermatologist at the clinic and polyclinic for dermatology and venereology at the University Hospital Cologne, the CMMC and the Excellence Cluster for Ageing Research at the University of Cologne in order to investigate ways to implement this approach.
A surgical team at UC San Diego Health has completed the first series of operations with a novel surgical system that can remove a diseased gallbladder through a single incision hidden in the belly button.
Santiago Horgan, MD, chief of minimally invasive surgery, was able to successfully remove the gallbladder through a 15-millimeter incision – roughly half an inch. This is believed to be the smallest reported successful incision for this procedure.
“What we are seeing is the rapid evolution of traditional laparoscopy toward less and smaller incisions — just one tiny incision, in fact,” said Horgan, professor of surgery and director of the Center for the Future of Surgery, UC San Diego School of Medicine. “Normally, a gallbladder removal would be performed with four incisions across the abdomen. We achieved the surgery with one small cut hidden in the umbilicus. So not only are there fewer incisions, the one that remains is incredibly small.”
Horgan said the new approach is dramatically better for patients in terms of healing and appearance. He cited fewer incision site complications, less post-operative pain, reduced chance of hernia, faster recovery and exceptional cosmetic outcomes as potential benefits. The 30-minute procedure was performed under general anesthesia. Patients returned home the same day with no complications. Approximately 600,000 people per year have their gallbladder surgically removed in the United States.
UT Southwestern Medical Center researchers successfully boosted the regeneration of mature nerve cells in the spinal cords of adult mammals – an achievement that could one day translate into improved therapies for patients with spinal cord injuries.
“This research lays the groundwork for regenerative medicine for spinal cord injuries. We have uncovered critical molecular and cellular checkpoints in a pathway involved in the regeneration process that may be manipulated to boost nerve cell regeneration after a spinal injury,” said senior author Dr. Chun-Li Zhang, Associate Professor of Molecular Biology at UT Southwestern.
Dr. Zhang cautioned that this research in mice, published today by Cell Reports, is still in the early experimental stage and is not ready for clinical translation.
“Spinal cord injuries can be fatal or cause severe disability. Many survivors experience paralysis, reduced quality of life, and enormous financial and emotional burdens,” said lead author Dr. Lei-Lei Wang, a postdoctoral researcher in Dr. Zhang’s lab whose series of in vivo (in a living animal) screens led to the findings.
Spinal cord injuries can lead to irreversible neural network damage that, combined with scarring, can ultimately impair motor and sensory functions. These outcomes arise because adult spinal cords have very limited ability to regenerate damaged neurons to aid in healing, said Dr. Zhang, a W.W. Caruth, Jr. Scholar in Biomedical Research and member of the Hamon Center for Regenerative Science and Medicine.
Dr. Zhang’s lab focuses on glial cells, the most abundant non-neuronal type of cells in the central nervous system. Glial cells support nerve cells in the spinal cord and form scar tissue in response to injury. In 2013 and 2014, the Zhang laboratory created new nerve cells in the brains and spinal cords of mice by introducing transcription factors that promoted the transition of adult glial cells into more primitive, stem cell-like states, and then coaxed them to mature into adult nerve cells.
The number of new spinal nerve cells generated by this process was low, however, leading researchers to focus on ways to amplify adult neuron production.
In a two-step process, researchers first silenced parts of the p53-p21 protein pathway that acts as a roadblock to the reprogramming of glial cells into the more primitive, stem-like types of cells with potential to become nerve cells. Although the blockade was successfully lifted, many cells failed to advance past the stem cell-like stage. In the second step, mice were screened for factors that could boost the number of stem-like cells that matured into adult neurons. They identified two growth factors – BDNF and Noggin – that accomplished this goal, Dr. Zhang said. Using this approach, researchers increased the number of newly matured neurons by tenfold.
“Silencing the p53-p21 pathway gave rise to progenitor (stem-like) cells, but only a few matured. When the two growth factors were added, the progenitors matured by the tens of thousands,” Dr. Zhang said.
Further experiments that looked for biomarkers commonly found in nerve cell communication indicated that the new neurons may form networks, he added.
“Because p53 activation is thought to safeguard cells from undergoing uncontrolled proliferation, as in cancer, we followed mice that had temporary inactivation of the p53 pathway for 15 months without observing any increased cancer risk in the spinal cord,” he said.
“Our ability to successfully produce a large population of long-lived and diverse subtypes of new neurons in the adult spinal cord provides a cellular basis for regeneration-based therapy for spinal cord injuries. If borne out by future studies, this strategy would pave the way for using a patient’s own glial cells, thereby avoiding transplants and the need for immunosuppressive therapy,” Dr. Zhang said.
A study by a multidisciplinary team of researchers from The Saban Research Institute of Children’s Hospital Los Angeles sheds further light on the role of the cytokine TGFβ1 in the growth of neuroblastoma, and suggests the possibility for a small molecule drug/antibody combinatorial therapy to treat this cancer. Their data has been published online by the journal Clinical Cancer Research.
Neuroblastoma (NB) is a type of solid cancer that arises from nerve tissues. It is the most common type of childhood cancer with nearly half of its incidence in children under two years of age and accounts for 15 percent of all childhood cancer deaths. Currently available therapy involves the use of an antibody called dinutuximab which targets a type of modified carbohydrate sugar (GD2) found to be expressed at high levels in NB tumors. However, this antibody-based treatment is often not sufficient to prevent cancer relapse.
In addition to directly targeting molecules involved in disease, in many cases antibody-based therapy is thought to also involve the activation of natural killer (NK) cells. NK cells are a subset of immune cells that have a proven capacity to kill tumor cells upon activation by antibodies. Proteins such as TGFβ1 (transforming growth factor beta 1) have recently been shown to suppress the anti-cancer functions of NK cells in the tumor microenvironment.
TGFβ1, part of the superfamily of cytokines, is a secreted protein that performs many cellular functions including control of cell growth, proliferation, and cell death. The CHLA researchers demonstrate a unique mechanism for tackling NB by employing a combinatorial therapy involving dinutuximab and a small molecule drug, galunisertib, which inhibits TGFβ1. Grafting NB cell lines or tissue from a patient with neuroblastoma into immunodeficient mice, the authors demonstrate that galunisertib-mediated inhibition of TGFb1 allows dinutuximab and NK cells to effectively kill the NB tumors.
“The addition of galunisertib to adoptive cell therapy using natural killer cells in addition to the drug dinutuximab reduced tumor growth and increased the survival of mice injected with either neuroblastoma cell lines or patient-derived tumor tissue,” said principal investigator Robert Seeger, MD, of CHLA’s Center for Childhood Cancer and Blood Disease. Seeger is also a professor of pediatrics with the Keck School of Medicine of the University of Southern California (USC). He added that galunisertib reverses the TGFβ-1-induced suppression of cytotoxicity and may improve antibody-based immunotherapy for neuroblastoma.
The Journal of Headache and Pain published an open label study – Non-invasive Vagus Nerve Stimulation (nVNS) as mini-prophylaxis for menstrual/menstrually related migraine.
Menstrual migraine and menstrually related migraine attacks are typically longer, more disabling, and less responsive to medications than non-menstrual attacks. The aim of this study was to evaluate the efficacy, safety, and tolerability of non-invasive vagus nerve stimulation for the prophylactic treatment of menstrual migraine/menstrually related migraine.
Fifty-six enrolled subjects (menstrual migraine, 9 %; menstrually related migraine, 91 %), 33 (59 %) of whom were receiving other prophylactic therapies, entered a 12-week baseline period. Fifty-one subjects subsequently entered a 12-week treatment period to receive open-label prophylactic non-invasive vagus nerve stimulation adjunctively (31/51; 61 %) or as monotherapy (20/51; 39 %) on day −3 before estimated onset of menses through day +3 after the end of menses.
The number of menstrual migraine/menstrually related migraine days per month was significantly reduced from baseline (mean ± standard error, 7.2 ± 0.7 days) to the end of treatment (mean ± standard error, 4.7 ± 0.5 days; P < 0.001) (primary end point). Of all subjects, 39 % (95 % confidence interval: 26 %, 54 %) (20/51) had a ≥ 50 % reduction (secondary end point). For the other secondary end points, clinically meaningful reductions in analgesic use (mean change ± standard error, −3.3 ± 0.6 times per month; P < 0.001), 6-item Headache Impact Test score (mean change ± standard error, −3.1 ± 0.7; P < 0.001), and Migraine Disability Assessment score (mean change ± standard error, −11.9 ± 3.4; P < 0.001) were observed, along with a modest reduction in pain intensity (mean change ± standard error, −0.5 ± 0.2; P = 0.002). There were no safety/tolerability concerns.
These findings suggest that non-invasive vagus nerve stimulation is an effective treatment that reduces the number of menstrual migraine/menstrually related migraine days and analgesic use without safety/tolerability concerns in subjects with menstrual migraine/menstrually related migraine. Randomised controlled studies are warranted.