MedicalResearch.com Interview with:
Dr Dilan Athauda MRCP
Sobell Department of Motor Neuroscience and Movement Disorders
UCL Institute of Neurology & The National Hospital for Neurology and Neurosurgery
London
MedicalResearch.com: What is the background for this study?
Response: Exenatide is a synthetic version of a naturally occurring protein - exendin-4 - that was originally discovered by Dr John Eng in the early 1990’s in the saliva of the Gila Monster, a venomous lizard native to the Southwestern United states. He and his team were looking for bio-active peptides in insect and lizard venom that could be useful for people with Type 2 diabetes. They discovered that exendin-4 was extremely similar to a human hormone called Glucagon-like peptide-1 (GLP-1). In humans, GLP-1 is secreted after you eat a meal to stimulate insulin secretion (and inhibit glucagon production) of which the end result is a lowering of blood sugar. Unfortunately human GLP-1 is rapidly broken down by a circulating enzyme called dipeptidyl peptidase IV (DPP-IV) and its effects only last minutes.
Importantly, it was discovered that exendin-4 is naturally resistant to the actions of this enzyme, meaning it’s effects on blood sugar control lasts much longer in the body. These properties made it very attractive to people trying to treat people with Type 2 diabetes and following many successful randomised controlled trials of patients with Type 2 diabetes in 2005, exenatide was approved for use as a treatment. During this time, work led by Nigel Greig’s group at the NIA showed that first evidence that exendin-4 had neuroprotective properties, and could protect neurons from a variety of stresses and could also improve growth and rescue degenerating cells. Over the next few years, various groups used exendin-4 in a variety of animal toxin models of
Parkinson’s disease and showed that exendin-4 could halt the progression of Parkinsonism and prevent cell death in these models through beneficial effects on inflammation, mitochondrial function and cell survival.
Based on this encouraging pre-clinical data, Professor Foltynie supervised the first small, “open-label”, human trial of exenatide in patients with Parkinson’s disease. The team found that patients treated with exenatide for 1 year (in addition to their usual medication) had less decline in their motor symptoms when assessed without their medication compared to the control group (just on their usual medication) and this advantage over the control group was still present 1 year after stopping the exenatide injections. However, this trial was open-label – patients knew they were getting a (potentially beneficial) experimental therapy and so we couldn’t exclude the fact that placebo effects were explaining some of the results we saw.
As a result of the potentially beneficial results seen in this small open label trial we carried out a double-blind, placebo controlled trial.
Prof. Harding[/caption]
Jane E. Harding, DPhil
Liggins Institute
The University of Auckland
Auckland, New Zealand
MedicalResearch.com: What is the background for this study?
Response: Neonatal hypoglycaemia – low blood sugars in newborns – affects up to one in six babies born. It involves a sustained dip in blood sugar levels following birth. Blood glucose is the only fuel for babies’ brains (adults have alternative, back-up sources). So, if left untreated, this condition can cause developmental brain damage and lowered education outcomes later in life.
In developed economies, as many as a third of babies born are at risk. Risk factors include being born smaller or larger than usual, preterm babies and babies whose mothers have any form of diabetes – this last a growing group, with the rising incidence of gestational (pregnancy-related) diabetes.
We wanted to systematically track a cohort of babies to see if hypoglycaemia in babies affects their long-term health and development. So we designed the CHYLD study – Children with Hypoglycaemia and their Later Development. We are following 614 New Zealand babies born at risk of low blood sugar levels (neonatal hypoglycemia) into childhood to see if the condition affects their later growth and development. Our team includes researchers from the Liggins Institute, the University of Auckland, Waikato Hospital, the University of Canterbury and the University of Waterloo.
Half of the babies in the study were diagnosed with, and treated for low blood sugars. Seventy percent received extra, continuous monitoring of their blood sugar levels, which detected in some babies low levels that were not diagnosed by the heel-prick tests.
Dr. Ash[/caption]
Arlene S. Ash, PhD
Department of Quantitative Health Sciences
University of Massachusetts Medical School
Worcester
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: State Medicaid programs (and other health care purchasers) often contract with several managed care organizations, each of which agrees to address all health care needs for some of their beneficiaries. Suppose a Medicaid program has $5000 to spend, on average, for each of its 1 million beneficiaries. How much should they pay health plan “A” for the particular 100,000 beneficiaries it enrolls? If some group, such as those who are homeless, is much more expensive to care for than the payment, plans that try to provide good care for many such people will go broke. We describe the model now used by MassHealth to ensure that plans get more money for enrolling patients with greater medical and social needs. In this medical-social model, about 10% of total dollars is allocated by factors other than the medical-morbidity risk score.
Dr. Hernandez[/caption]
Inmaculada Hernandez, PharmD, PhD
Assistant Professor of Pharmacy and Therapeutics
University of Pittsburgh School of Pharmacy
Pittsburgh, PA 1526
MedicalResearch.com: What is the background for this study?
Response: A few months ago, the results of the FOURIER trial were published. This trial was the first one to evaluate the efficacy of PCSK9 inhibitors in the prevention of cardiovascular events, since the approval of these agents was based on trials that evaluated their efficacy in reducing levels of LDL-C. The results of the FOURIER trial did not meet the expectations generated by prior studies that had simulated how much the risk of cardiovascular events should decrease based on the observed reduction in LDL-C levels. A few hours after the publication of the results of the FOURIER trial, Amgen (evolocumab´s manufacturer) announced that it would be willing to engage in contracts where the cost of evolocumab would be refunded for those patients who suffer a heart attack or a stroke while using the drug.
Dr. Jordan[/caption]
Stanley C. Jordan, M.D
Director, Division of Nephrology
Medical Director, Kidney Transplant Program
Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory
Cedars-Sinai, Los Angeles, CA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The background for this study is as follows: Patients who are highly HLA sensitized have antibodies to transplant targets create an immunologic barrier to transplant. Currently, there are no approved therapies for elimination of these antibodies. Desensitization is available but is not always successful and most desensitized patients are still transplanted with a positive crossmatch. Thus, many patients are not able to receive life-saving kidney transplants unless newer therapies to remove antibodies are found.
The findings of our study published in the New England Journal of Medicine revealed that the use of the enzyme from streptococcal pyogenes called IdeS® (IgG endopeptidase) is very effective in eliminating donor specific antibodies and allowing transplantation to occur. Antibodies were eliminated from one week up to two months after one treatment with Ides® allowing a safe environment for the transplant to occur. Rejections episodes did occur in some of the patients but were generally mild and easily treatable. Only one patient of 25 lost his allograft during the study. Thus, the study shows promising results for a new approach for elimination of pathogenic antibodies that did not exist before.
Dr.Enderling[/caption]
Heiko Enderling, Ph.D.
Associate Member & Director for Education and Outreach
Dept. of Integrated Mathematical Oncology
Dept. of Radiation Oncology
H. Lee Moffitt Cancer Center & Research Institute
Tampa, FL 33612
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Although radiation therapy after breast-conserving surgery for early-stage breast cancer has significantly improved patient prognosis, many patients will face a second cancer diagnosis within 20 years of primary treatment. Experimental and clinical studies have shown that local radiation therapy can activate an immune response that can propagate systemically to attack distant untreated metastases. However, current radiotherapy practice has not specifically focused on enhancing immune responses.
We asked the question if pre-operative irradiation, when applied to the bulk of disease, could have potentially higher immune stimulatory effects. To study this, we analyzed historic outcomes of breast cancer patients treated with either adjuvant (radiation after surgery) or neoadjuvant (radiation before surgery) radiotherapies.
Our analysis showed that the risk of developing a second tumor after neoadjuvant compared with adjuvant RT was significantly lower, especially for estrogen receptor-positive women who underwent
Dr. Kochunov[/caption]
Peter Kochunov PhD
Professor
Maryland Psychiatric Research Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Schizophrenia is a debilitating disorder that strikes young people at the point of entering adulthood. In the past, we and others demonstrated that patients with schizophrenia are characterized by deficits in the white matter of the brain. White matter is the part of the brain that serves the backbone of cerebral networks transmitting information and interconnecting brain regions.
In this report, we link the impaired white matter of the brain in schizophrenia patients with the disorder-related deficits in the processing speed. We also showed that mental processing speed is a fundamental cognitive construct that partially supports other functions like working memory in patients, where processing speed acting as the intermediate between white matter deficits and reduced working memory. This interesting relationship between processing speed, working memory, and white matter is most obvious in white matter regions most vulnerable to schizophrenia. That was the main finding of the study.
Dr. Jacobs[/caption]
Dr. Lisa K. Jacobs MD
Johns Hopkins School of Medicine
Baltimore, Maryland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Breast preservation is the preferred treatment for many women diagnosed with breast cancer. The most common question that a patient will ask after the surgery is, “Did you get it all?” In the ideal case, this is accomplished in a single outpatient surgery with very good cosmetic results. In our study, Beyond the Margins-Economic Costs and Complications Associated with Repeated Breast-Conserving Surgeries we evaluated the detrimental effects of an unsuccessful initial surgery due to positive surgical margins. Using private insurance claims data, we found that 16% of patients planning breast preservation required a second breast-conserving surgery and an additional 7% converted to mastectomy. Of those patients that required additional surgery there was a 56% ($16,072) increase in cost and a 48% increase in complications. Those complications include infection, hematoma, seroma, and fat necrosis. This study demonstrates that repeated surgery has not only cosmetic consequences, but also has financial implications and increased risk.
Dr. Adrian Harel[/caption]
Dr. Adrian Harel, PhD
Chief Executive Officer
Medicortex Finland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Every 15 seconds, someone in the United States suffers a new head injury. Of the 2.5M people treated in hospital emergency rooms each year, 80,000 become permanently disabled because of TBI. Currently, there are no reliable diagnostic tests to assess the presence or severity of an injury on-site, nor are there any pharmaceutical therapies that could stop the secondary injury from spreading. Accurate diagnostics would benefit especially mild cases of TBI (concussions), which, if occurring repeatedly, may cause neurodegenerative conditions such as Chronic Traumatic Encephalopathy (which is typical for athletes in NFL and Ice-hockey).
We have performed extensive preclinical research comparing fluid biopsies from normal and injured lab animals. The results showed some unique biomarkers released as a biodegradation products after head injury. The data served as the basis and confirmation for our patent applications to protect the biomarker concept.
Medicortex has completed a clinical proof-of-concept trial in collaboration with Turku University Hospital (Tyks). Samples from 12 TBI patients and 12 healthy volunteers were collected and analyzed for the presence and for the level of the biomarker in state-of-the-art laboratories. The study demonstrated the diagnostic potential of the new biomarker in humans and it confirmed the prior preclinical findings. This was a significant milestone for Medicortex.
