Syndicate content

Archive

March 11th, 2019

tACS (Transcranial Alternating Current Stimulation) of Brain Improves Symptoms of Major Depression, Restores Brain Waves in Clinical Study; New Approach Might Significantly Help Depressed Patients in Inexpensive, Non-Invasive Way, Lead Researcher Says

University of North Carolina (UNC) School of Medicine researchers, led by Flavio Frohlich, Ph.D., are the first to use transcranial alternating current brain stimulation (tACS) to significantly reduce symptoms in people diagnosed with major depression. With a weak alternating electrical current sent through electrodes attached to the scalp, University of North Carolina (UNC) School of Medicine researchers successfully targeted a naturally occurring electrical pattern in a specific part of the brain and markedly improved depression symptoms in about 70 percent of participants in a clinical study. The research, published online on March 5, 2019 in Translational Psychiatry, lays the groundwork for larger research studies to use a specific kind of electrical brain stimulation called transcranial alternating current stimulation (tACS) to treat people diagnosed with major depression. The open-access article is titled “Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD).” "We conducted a small study of 32 people because this sort of approach had never been done before," said senior author Flavio Frohlich, PhD, Associate Professor of Psychiatry and Director of the Carolina Center for Neurostimulation. "Now that we've documented how this kind of tACS can reduce depression symptoms, we can fine-tune our approach to help many people in a relatively inexpensive, noninvasive way." Dr. Frohlich, who joined the UNC School of Medicine in 2011, is a leading pioneer in this field who also published the first clinical trials of tACS in schizophrenia and chronic pain. Dr.

Roche's VENTANA PD-L1 (SP142) Assay Approved As First Companion Diagnostic to Identify Triple-Negative Breast Cancer Patients Eligible for Treatment with Tecentriq in Combination with Abraxane

On March 11, 2019, Roche (SIX: RO, ROG; OTCQX: RHHBY) announced the the US Food and Drug Administration had approved the VENTANA PD-L1 (SP142) Assay as the first companion diagnostic to aid in identifying triple-negative breast cancer (TNBC) patients eligible for treatment with the Roche cancer immunotherapy Tecentriq® (atezolizumab) plus chemotherapy (Abraxane® [paclitaxel protein-bound particles for injectable suspension (albumin-bound); nab-paclitaxel]). Assessment of PD-L1 biomarker status on tumor-infiltrating immune cells with the assay is essential for identifying those patients most likely to benefit from the treatment. A diagnosis of triple-negative breast cancer means that the three most common proteins associated with breast cancer growth (estrogen receptor, progesterone receptor, and HER2/neu) are not expressed on the tumor. "Triple-negative breast cancer is an aggressive disease that, until now, has had limited treatment options," said Michael Heuer, CEO of Roche Diagnostics. "This assay plays a pivotal role in helping physicians identify patients who can benefit from Tecentriq therapy, providing better patient care. At Roche, we build on our capacity to research both targeted medicines and companion diagnostics under one roof, so we can provide the right treatment to the right patient at the right time." Each year about 300,000 women are diagnosed globally with triple-negative breast cancer, an aggressive disease with limited treatment options that represents 15 percent of all breast cancer cases. The VENTANA PD-L1 (SP142) Assay was developed to enhance visual contrast of tumor-infiltrating immune cell staining. In triple-negative breast cancer, PD-L1 is primarily expressed on tumor-infiltrating immune cells rather than on tumor cells themselves.

FDA Grants Roche’s Tecentriq, in Combination with Abraxane, Accelerated Approval for People With PD-L1-Positive, Metastatic Triple-Negative Breast Cancer; First Cancer Immunotherapy Regimen Approved for Breast Cancer

On March 11, Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the US Food and Drug Administration (FDA) has granted accelerated approval to Tecentriq® (atezolizumab) (an anti-PD-L1 monoclonal antibody), plus chemotherapy (Abraxane® [paclitaxel protein-bound particles for injectable suspension (albumin-bound); nab-paclitaxel]), for the treatment of adults with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC) in people whose tumors express PD-L1, as determined by an FDA-approved test. “The FDA approval of this Tecentriq combination is an important treatment advance for people with PD-L1-positive, metastatic triple-negative breast cancer, a disease with high unmet medical need,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “This Tecentriq combination is the first cancer immunotherapy regimen to be approved in breast cancer, representing a meaningful step forward in the understanding of this disease.” This indication is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious or life-threatening disease or condition. This accelerated approval is based on data from the Phase III IMpassion130 study, which demonstrated that Tecentriq, plus nab-paclitaxel, significantly reduced the risk of disease worsening or death (PFS) by 40% compared with nab-paclitaxel alone (median PFS=7.4 vs.

March 9th

Minnesota Scientists Develop Small Peptide to Block Checkpoint Inhibition System in Brain, Possibly Enabling Immunotherapy Treatment of Glioblastoma; Success Seen in Dog Models; Stage 1 Human Clinical Trial Anticipated for Mid-Summer 2019

As sometimes happens in science, a seeming failure can occasionally lead to great success. That is the hope of University of Minnesota scientists Michael Olin (left in photo), PhD, and his colleague Chris Moertel (right in photo), MD, who have co-founded a new company, OX2 Therapeutics, together with Californian biotech entrepreneur Sumant Dhawan, in order to advance a promising peptide molecule into phase 1 human clinical trials for the treatment of glioblastoma, one of the deadliest brain tumors in humans. The peptide interferes with the dual paired receptor (CD200R1/CD200AR) immune checkpoint system to counter glioblastoma’s overproduction of soluble CD200 (originally named OX2) that acts to suppress the body’s immune response against the cancer. Drs. Olin and Moertel say that their team has developed a small peptide inhibitor (15 amino acids) to interfere specifically with this CD200 checkpoint inhibition system to empower the body’s own immune system to attack and defeat glioblastoma multiforme (GBM). In fact, based in part on the success of the addition of this peptide to tumor lysate vaccines in extending the lifespan of brachycephalic (short-nosed) dogs that naturally develop glioblastoma, CMO Dr. Moertel said that he “anticipates” that a phase 1 clinical trial of this peptide will begin in mid-summer 2019. This trial will be led by neuro-oncologist Elizabeth Neil, MD, Assistant Professor of Neurology at the University of Minnesota, and will include 14-18 adult glioblastoma patients who have experienced recurrent glioblastoma. Following successful treatment of 3 adult patients, the researchers plan to enroll 14-18 pediatric patients with recurrent glioblastoma, medulloblastoma, and/or ependymoma in a second arm of the trial, to be led by Assistant Professor Emily Greengard, MD, Department of Pediatrics at the University of Minnesota. Dr.

March 9th

Newly ID’d Pathway & Aging--NORAD (Non-Coding RNA Activated by DNA Damage) & PUMILIO Protein Play Key Roles in Maintenance of Genome Stability & Mitochondrial Function—Defects May Be Significant in Premature Aging Diseases Such As Progerias

Building upon their earlier discoveries, researchers at the University of Texas (UT) Southwestern have identified a new genetic pathway that prevents premature aging. Published online on February 8, 2019 in eLife, the study investigated the activity of the gene NORAD, which codes for a long noncoding RNA. The title of the article is “PUMILIO Hyperactivity Drives Premature Aging of Norad-Deficient Mice.” NORAD, which stands for “noncoding RNA activated by DNA damage,” is present in many mammals and helps maintain the appropriate number of chromosomes as cells divide. Many RNAs in the cell serve as the instructions, or code, for building proteins, whereas noncoding RNAs do not encode proteins. “There are many questions in the scientific community regarding the importance of noncoding RNAs in mammalian physiology and development,” said Dr. Joshua T. Mendell, Professor of Molecular Biology at UT Southwestern and senior author of the study. “Our cells produce thousands of these RNAs, but only a few have been connected to important functions in animals.” In 2015, the researchers reported their discovery of NORAD and demonstrated the importance of this noncoding RNA in maintaining the correct number of chromosomes in human cells. With their previous work limited to cells grown in the laboratory, the researchers next examined the role of NORAD in a living animal, in order to better understand the gene’s function in mammalian physiology. To accomplish this, Dr. Florian Kopp, a postdoctoral researcher in the Mendell lab and lead author of the eLife study, genetically engineered mice by deleting NORAD from the mouse genome. As has previously been found in human cells, the loss of NORAD caused chromosomal defects in mice. But there were also some unexpected changes to mitochondria, the energy powerhouses of the cell.

Exosomes Derived from PMSCs and Expressing Galectin 1 on Surface May Protect Neurons & Reduce Spinal Cord Injury, Offering Promising Prospect of Cell-Free Treatment, Spina Bifida Researchers at UC Davis Conclude

Researchers on the path to finding a cure for spina bifida have identified specific elements in stem cell secretions as key to protecting neurons and ultimately reducing the lower-limb paralysis associated with the birth defect. Those elements are exosomes (sub-cellular, membrane-bound vesicles that can transfer molecules from cell to cell) and a small carbohydrate-binding protein known as galectin 1. The research team will use the results to optimize the neuroprotective qualities of a stem cell treatment they have developed to improve the mobility issues associated with spina bifida. The new results were published online on February 12, 2019 in The FASEB Journal. The study was led by Aijun Wang (photo), PhD, Co-Director of the UC Davis Health Surgical Bioengineering Laboratory, and the article is titled “Neuroprotective Effect of Placenta-Derived Mesenchymal Stromal Cells: Role of Exosomes.” UC Davis Health fetal surgeon, and study co-author Diana Farmer, MD, Chair of the UC Davis Department of Surgery, first showed that prenatal surgery reduces neurological defects in children with spina bifida, which occurs when the spinal cord does not properly close before birth. Children with the condition experience a range of lifelong cognitive, urological, musculoskeletal and motor disabilities. Dr. Farmer, and Dr. Wang, her chief collaborator, later showed that prenatal surgery combined with human placenta-derived mesenchymal stromal cells (PMSCs) improved hind limb control in lab animals and dogs with spina bifida. Dr. Farmer is a Diana Farmer is a leader in research and surgical approaches to reduce the effects of spina bifida on children. “We wanted to know the specific mechanisms of action of the PMSC treatment that protect neurons,” Dr. Wang said.

Two Life-Saving Discoveries Help Four Generations of Women in One Family Deal with Familial Hypercholesterolemia; World-Leading Cholesterol Research at UT Southwestern Medical Center Led to Development of Game-Changing Statins, Then PCSK9 Inhibitors

Her great-grandmother volunteered in ground-breaking cholesterol research at the University of Texas (UT) Southwestern Medical Center. Now, 9-year-old Zoe Allen is benefiting from that decision. Four generations of women, who all have the same hereditary condition – familial hypercholesterolemia – form a story interwoven with the discovery of new treatments that have benefited millions of people. In 1987, Kathryn Geddie was a 33-year-old mother of two. At her annual physical, she told her doctor that her mother had extremely high cholesterol levels at a young age. After testing, Kathryn learned she had the same condition and began taking statins. “My mother is the reason that I was tested. My physician began treating me in 1987 because my cholesterol was in the upper 300s,” remembered Kathryn, now 64. Kathryn’s immediate concern drove her to have her then 11-year-old daughter, Shanon, tested. Despite her young age, Shanon’s cholesterol was soaring at 400 mg/dL. The normal range is less than 200. Little did the family know then that their shared struggle with high cholesterol would lead them on a road to reverse the disease – one paved by the generation that came before them. (Photo here shows Kathryn, Shannon, & Zoe--See additional, larger pics at end of this article). In the early 1980s, Kathryn’s mother, Estelle, took part in leading-edge research at UT Southwestern Medical Center where molecular genetics professors Drs. Michael Brown and Joseph Goldstein were seeking answers to how people develop high cholesterol. These scientists identified the basic mechanism of cholesterol metabolism, which led to their being awarded the 1985 Nobel Prize in Physiology or Medicine. Soon after this discovery, statins were developed to lower cholesterol and help prevent heart disease. Thousands of adult patients benefited. However, there were unknown risks for children.

March 7th

Cancer Commons & xCures, AI-Based Virtual Trial Companies, Invite Participation from Patients Who Try New Combination Therapy for Pancreatic Cancer; Highly Promising Results Just Published in Nature Medicine; Relevance to TV Game Show Host Alex Trebek

Treatment for metastatic pancreatic cancer (pancreatic ductal adnocarcionoma or PDA) has seen progress in recent years, but outcomes remain poor and treatment advances that can prolong patients’ lives, even for a few months, are eagerly awaited. Two papers, just published online on March 4, 2019 in Nature Medicine (https://www.nature.com/articles/s41591-019-0368-8) (https://www.nature.com/articles/s41591-019-0367-9), suggest that a new combination of two existing drugs (an autophagy inhibitor and an inhibitor of the downstream metabolic pathway activated by mutated KRAS), which are both already FDA-approved for other conditions, may significantly delay progression of pancreatic cancer in human PDA cells in vitro and in PDA-derived tumors in mice. Furthermore, the first patient treated with this combination experienced a prolonged response that lasted almost six months. In light of these promising results, Cancer Commons (https://www.cancercommons.org/) is partnering with xCures (https://www.xcures.com/) to track the experiences of patients who choose to try this new combination therapy. This effort is particularly relevant given the March 6 announcement by TV Jeopardy game show host Alex Trebek that he has been diagnosed with stage 4 pancreatic cancer. The two Nature Medicine studies came from The Huntsman Cancer Institute at the University of Utah and from the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill.

March 5th

First Novel Drug Mechanism Approved for Major Depression in Decades; FDA Approves Fast-Acting SPRAVATO™ (Esketamine, Derivative of Ketamine) Nasal Spray for Adults with Treatment-Resistant Depression

On March 5, 2019, Janssen Pharmaceutical Companies of Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved SPRAVATO™ (esketamine, a derivative of ketamine) CIII nasal spray for use, in conjunction with one of a number of existing oral antidepressant, in adults with treatment-resistant depression (TRD). People who are currently struggling with major depressive disorder (MDD) are considered to have TRD if they have not responded adequately to at least two different antidepressants of adequate dose and duration in the current depressive episode. It is estimated that approximately one-third of U.S. adults with MDD have TRD. "It was hard to have any emotions, because I was just numb," said Robin P., an esketamine clinical trial patient. "When I began treatment with esketamine and my symptoms started to lift, I could see very clearly just how depressed I had been. I'm now able to appreciate a wider range of emotions than when I was depressed. My long-term goals have taken shape and actually seem attainable." Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two enantiomers (mirror-image molecules). This is the first FDA approval of esketamine for any use. The FDA approved ketamine (Ketalar) in 1970. "SPRAVATO™ has the potential to change the treatment paradigm and offer new hope to the estimated one-third of people with major depressive disorder who have not responded to existing therapies," said Mathai Mammen, MD, PhD, Global Head, Janssen Research & Development, LLC. "This unique and innovative medicine is a testament to Janssen's heritage of advancing solutions in neuroscience to heal minds and improve health outcomes."

March 5th

NIH Hosts Rare Disease Day; Countries Around World Stage Similar Events Marking Significance of 7,000 Individually Rare Diseases That, When Taken Together, Afflict Over 400 Million People; Many Are Grievously Affected Children with Genetic Diseases

On Thursday, February 28, 2019, the US National Institutes of Health (NIH) hosted its ninth annual Rare Disease Day (RDD) event, which included a feature address b NIH Director Francis Collins, MD, PhD, and is held to raise awareness, report progress, and speed advances for patients afflicted by the estimated 7,000 “rare diseases” that exist throughout the world. Approximately 80 percent of these rare diseases are genetic in origin, with more than half affecting children, and many being life-threatening. Although rare when viewed individually, these diseases--such as giant axonal neuropathy (GAN) (50 affected families in world) which the little girl Amber (https://www.friendsatnih.org/hope-for-amber/) (https://childrensinn.org/amber/) in the photo has (see much larger version of this photo at end of story), Fabry disease (8,000 in US), Niemann-Pick Type C (2,200 in US), hemophilia (18,000 in US), ALS (Lou Gehrig’s disease) (20,000 in US), cystic fibrosis (30,000 in US), and sickle cell anemia (100,000 in US)-- affect an estimated 400 million people around the world. These numbers can be contrasted with those for some common diseases such as type 2 diabetes (21 million in US), Alzheimer’s (5.7 million in US), invasive breast cancer in women (predicted 270,000 new cases expected to be diagnosed in 2019 in US), malaria (212 million cases worldwide in 2015), and tuberculosis (2 billion infected worldwide). (Editor's Note: In the US, rare diseases are defined as those affecting 200,000 or fewer people in the country of over 325 million.)