Diabetes Medication Exenatide Shows Promise In Treating Parkinson’s Disease

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.

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Skin-Grafted Stem Cells May Treat Obesity and Diabetes

MedicalResearch.com Interview with:

Dr. Xiaoyang Wu PhD Ben May Department for Cancer Research The University of Chicago, Chicago, IL

Dr. Xiaoyang Wu

Dr. Xiaoyang Wu PhD
Ben May Department for Cancer Research
The University of Chicago, Chicago, IL

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have been working on skin somatic stem cells for many years. As one of the most studies adult stem cell systems, skin stem cells have several unique advantages as the novel vehicle for somatic gene therapy (summarized also in the paper). The system is well established. Human skin transplantation using CEA device developed from skin stem cells have been clinically used for decades for burn wound treatment, and been proven to be safe the effective.

In this study, we developed a skin 3D organoid culture model to induce stratification and maturation of mouse epidermal stem cells in vitro, which allows us to efficiently transfer engineered mouse skin to isogenic host animals. In the proof of concept study, we showed that we can achieve systematic release of GLP1 at therapeutic concentration by engineered skin grafts.

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Diabetic Retinopathy May Impact Daily Work and Activities

MedicalResearch.com Interview with:

Jeffrey R. Willis MD, PhD 

Dr. Willis

Jeffrey R. Willis MD, PhD
UC Davis Eye Center
University of California, Davis
Sacramento California

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Diabetic retinopathy is one of the leading causes of blindness in the United States.  Yet there is limited national level data on the impact of worsening DR on quality of life and visual function.

Our study aimed to address this knowledge gap by evaluating the functional burden of DR across severity levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES).

We found that one-half of US adults with severe non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) had difficulty with ≥ 1 visual function task, possibly impacting their daily work/activities.  These patients reported a significantly greater vision-related functional burden relative to those with less severe forms of DR.

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Erectile Dysfunction Should Be a Marker For Diabetes

MedicalResearch.com Interview with:

Damiano Pizzol  Operational Research Unit, Doctors with Africa Cuamm Beira, Mozambique

Damiano Pizzol 

Damiano Pizzol 
Operational Research Unit, Doctors with Africa Cuamm
Beira, Mozambique

MedicalResearch.com: What is the background for this study?

Response: Since the 1970s the association between diabetes and the development of erectile dysfunction has been documented both in animal models and humans Several studies have considered the prevalence of erectile dysfunction in diabetes and the majority agree that the incidence of erectile dysfunction in men with diabetes is two- to three-fold higher than in the general population. It is estimated that erectile dysfunction affects up to 75% of all men with diabetes, it is age correlated and occurs at a younger age in men with diabetes.
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Women With Early Menopause At Higher Risk of Diabetes

MedicalResearch.com Interview with:

Eralda Asllanaj Department of Epidemiology Erasmus University Medical Center Rotterdamthe Netherlands

Eralda Asllanaj

Eralda Asllanaj
Department of Epidemiology
Erasmus University Medical Center
Rotterdamthe Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It is known that women with early onset of menopause (age below 45 years) have an increased risk of cardiovascular disease and overall mortality. This increased risk is thought to be due to the adverse effects of menopause on cardiovascular risk factors.

Type 2 diabetes is a major risk factor for cardiovascular disease, but it remains unclear whether age at menopause affects the risk of developing type 2 diabetes. Our study shows that women who experience menopause before the age of 40 were almost 4 times more likely to develop type 2 diabetes than those experiencing menopause after 55 years old. Moreover, those who had menopause between 40 to 44 years were 2.4 times more likely to have diabetes later in life. The risk of having diabetes reduced by 4 % per year older the women experienced menopause. Adjustment for the various confounding factors and differences in genetic predisposition to early menopause did not affect the results.

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Novo Nordisk and Glooko Launch Cornerstones4Care® App To Help Manage Diabetes

MedicalResearch.com Interview with:

David Moore MBA Senior Vice President of Marketing Novo Nordisk 

David Moore

David Moore MBA
Senior Vice President of Marketing
Novo Nordisk 

MedicalResearch.com: What is the Cornerstones4Care Powered by Glooko (C4C) App?

Response: The Cornerstones4Care® Powered by Glooko® App marries Novo Nordisk’s extensive knowledge of diabetes and personalized patient support with Glooko’s digital platform and data analytics expertise. The App is comprehensive tool that helps patients track meals, activity, medicine and blood sugar – in one convenient place – and is intended to help people learn how to better manage diabetes through their mobile devices.

MedicalResearch.com: What functions will people with diabetes have access to? How can the app help people living with diabetes control their disease?   

Response: The Cornerstones4Care® Powered by Glooko® App marries Novo Nordisk’s extensive knowledge of diabetes and personalized patient support with Glooko’s digital platform and data analytics expertise. The App is comprehensive tool that helps patients track meals, activity, medicine and blood sugar – in one convenient place – and is intended to help people learn how to better manage diabetes through their mobile devices.

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Supply and Demand for Diabetes Prevention Programs

MedicalResearch.com Interview with:

Maria L. Alva, DPhil Economist RTI International -  Research Triangle Institute

Dr. Alva

Maria L. Alva, DPhil
Economist
RTI International –  Research Triangle Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have strong evidence from trials of structured lifestyle intervention programs (e.g. the Diabetes Prevention Program (DPP)) showing that half of new diabetes cases could be avoided if persons with prediabetes changed their lifestyle habits to lose a modest amount of body weight. Moreover, the DPP has been successfully translated into cost-effective community-based prevention interventions, but nationally, these evidence-based interventions (EBIs) are not being used sufficiently. To scale up the implementation of diabetes prevention EBIs, we need to address the challenges of getting organizations to adopt EBIs, and community members to enroll.

Because cost is a primary barrier we wanted to understand what was the perceived value and demand for diabetes prevention programs in NC. And in particular, the role that community health workers and technology could play in program delivery, from the perspectives of both potential recipients (adults at high risk or diagnosed with prediabetes) and decision-makers in healthcare/public health delivery.

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Eyedrop Kallikrein Inhibitor Shows Promise for Diabetic Macular Edema

MedicalResearch.com Interview with:
Dr. David Kita, PhD Founder and Head of R&D Verseon CorporationDr. David Kita, PhD
Founder and Head of R&D
Verseon Corporation

MedicalResearch.com: What is the background for this study?

Dr. Kita: The preclinical data presented at the 2017 BIO International Conference provided details about Verseon’s plasma kallikrein inhibitors for the treatment of diabetic macular edema (DME).

DME affects millions of people worldwide and is a major cause of vision loss in patients with diabetes mellitus. Upregulation of the kallikrein-kinin system in response to diabetes can result in retinal vascular permeability, which can damage the retina and eventually lead to the central vision loss associated with DME.

The current treatment options for DME include intravitreal injections of anti-VEGF agents or corticosteroids into the eye and surgical laser treatments. Long-term use of intravitreal injections is associated with side effects such as inflammation, infections, and cataracts. For anti-VEGF drugs in particular, there is also a growing concern about geographic atrophy. In addition, about 50% of patients reported at most moderate vision improvements following anti-VEGF therapy in clinical trials. This highlights the need for a new treatment that can serve as a monotherapy or as an adjuvant to current therapies.

At Verseon, we are working on inhibitors of the serine protease plasma kallikrein (KLKB1) that can be administered either topically or orally. Verseon’s unique computer-driven drug discovery platform allows us to design potent, selective drug candidates that are unlikely to be found using traditional approaches. We have generated a number of chemically distinct series of KLKB1 inhibitors and optimized multiple lead candidates, which show good activity, permeability, and solubility.

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Newer Insulin Formulation Reduces Risk of Hypoglycemia

MedicalResearch.com Interview with:

Wendy Lane MD Director of Clinical Research Mountain Diabetes and Endocrine Center Asheville, NC 

Dr. Lane

Wendy Lane MD
Director of Clinical Research
Mountain Diabetes and Endocrine Center
Asheville, NC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The SWITCH1 trial was the first double blinded insulin trial to compare the rate of severe, nocturnal severe and symptomatic blood glucose-confirmed hypoglycemia between two basal insulins, insulin glargine U100 and insulin degludec U100, in patients with type 1 diabetes.

The trial design (double blinded crossover treat-to-target) eliminated any bias in the results, which showed clear-cut reductions in all categories of hypoglycemia with insulin degludec compared to insulin glargine.

Severe hypoglycemia has dangerous and greatly feared consequences including cognitive impairment, seizures, coma and death, and it is the main barrier to effective use of insulin in the treatment of type 1 diabetes. Insulin degludec, which was shown to reduce the risk of hypoglycemia compared to insulin glargine in the SWITCH1 trial, should be viewed by clinicians as an advancement in insulin therapy which will increase its safety and improve the quality of life of our patients with type 1 diabetes.

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Vitamin A Derivative May Have Anti-Diabetic Capabilities

MedicalResearch.com Interview with:

Stefan Amisten, PhD The Oxford Centre for Diabetes, Endocrinology & Metabolism University of Oxford, Oxford Diabetes Research Group, Division of Diabetes & Nutritional Sciences King’s College London, Faculty of Life Sciences & Medicine, London UK

Dr. Armisten

Stefan Amisten, PhD
The Oxford Centre for Diabetes, Endocrinology & Metabolism
University of Oxford, Oxford
Diabetes Research Group, Division of Diabetes & Nutritional Sciences
King’s College London, Faculty of Life Sciences & Medicine, London
UK

MedicalResearch.com: What is the background for this study?

Response: Type 2 diabetes is a global epidemic that is causing an increasing medical and financial burden on both individuals and society in general. Type 2 diabetes is characterized by insulin resistance, poor insulin response to blood glucose which leads to chronically elevated blood glucose and damage to the cardiovascular system and other organs, which may ultimately lead to blindness, kidney failure, blindness, toe amputations, cardiovascular disease and premature death. Although a number of drugs are available for the treatment of Type 2 diabetes, no drug is currently able to cure diabetes, as they are only able to slow down the disease progression. There is therefore a need to develop novel therapies to treat Type 2 diabetes.

G-protein coupled receptors (GPCRs) constitute a family of almost 400 cell surface receptors that is the target of a large number of modern medicines. Interestingly, only a small subset of all GPCRs are currently targeted by modern medicines, which means that a large number of GPCRs still have untapped therapeutic potential, largely because they have not been studied in-depth, or because their ligands (i.e. binding partners) have not been identified.

This study is a result of a thorough cataloguing of all G-protein coupled receptors (GPCRs) in human pancreatic islets (Amisten et al. Pharmacol Ther. 2013 Sep;139(3):359-91.), where the receptor GPRC5C was identified as one of the most abundant orphan GPCRs in human islets.

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