Scientists in the Program for Neurology Research & Discovery published 22 articles in peer-reviewed scientific journals in 2015, and are starting 2016 with three more articles accepted for publication. Read the publications here:
Here is a summary of the PNR&D’s ongoing work:
The role of inflammation in ALS pathogenesis
The goal of this project is to identify biomarkers that will allow us to diagnose ALS, better assess progression of the disease, and ultimately expand our understanding of how inflammation and the immune system contribute to ALS pathogenesis.
The role of epigenetic modifications in ALS pathogenesis
Our epigenetic research could enable insight into the mechanisms underlying sporadic ALS onset to facilitate the identification of effective therapies, early diagnosis, and potentially early-stage therapeutic interventions to increase survival outcomes in ALS patients.
Stem cell therapy for ALS
Dr. Eva L. Feldman is the PI of the first-in-human clinical trial investigating the use of intraspinal stem cell transplantation for the treatment of ALS. After Phase 1 results established safety of the stem cell transplantation surgeries, a Phase 2 trial investigated stem cell dosing and efficacy. In this trial, which began in September 2013 and was completed July 2014, 18 patients received increasing doses of cells ranging from 2 million to 16 million cells. Intraspinal transplantation of up to 16 million stem cells in patients with amyotrophic lateral sclerosis (ALS) was safe and well-tolerated, and caused no acceleration in disease progression. Due to these promising results we are currently planning the next Phase 2/3 trial.
Stem cell therapy for Alzheimer’s disease
Our long-term objective is to develop a breakthrough treatment for AD patients. Our approach combines the benefits of generating healthy new cells while protecting functional circuitry, thanks to a unique line of human stem cells we have developed in collaboration with Neuralstem, Inc. In preliminary experiments in animal models of early-onset AD, stem cells improved memory and cognitive deficits, of which even a modest improvement could significantly impact quality of life for a patient. Parallel studies are ongoing to determine exactly how these stem cells impact behavior, cognition and disease pathology in rodent models and to confirm safety in large animals, and will follow a similar preclinical pipeline to that used to bring our ALS stem cell therapy to trial. Within the next 18 months we aim to complete the necessary experiments to progress to an FDA-approved clinical trial in AD patients.
Alzheimer’s disease and diabetes
PNR&D investigators are studying the mechanisms underlying the interaction of these two pandemic diseases. Successful completion of these studies will give a fundamental basis for drug development and lifestyle modifications aimed at treating and/or preventing diabetes and Alzheimer’s disease. In a second project, scientists in the PNR&D are working to understand how obesity-related insulin resistance in neurons impacts cognitive impairment and Alzheimer’s disease pathology. A better understanding of this relationship will aid in the development of much-needed therapies to treat and prevent Alzheimer’s disease onset and progression in obese or diabetic individuals.
Diabetic neuropathy: basic science research
These studies are improving our understanding of how multiple complications develop and progress, determining biomarkers that reflect disease states and responsiveness to treatments, and enabling development of new comprehensive treatment strategies that target common pathways in diabetic complication-prone tissues that can be translated to patients. As part of an additional multi-investigator project, the PNR&D is examining energetic pathways involved in the onset of complications in nerve, kidney, and eye, in an effort to define changes in cellular metabolism that drive the development of diabetic complications. By studying neuronal changes in patients with diabetic neuropathy, we have discovered some of the key mechanistic pathways involved in neuronal injury during diabetes. These pathways have become the subjects for development of new, groundbreaking therapies.
Diabetic neuropathy: clinical research
We recently reported that diabetic neuropathy in type 1 and type 2 diabetes may result from differing pathogenic insults, as determined by reviewing results from a number of clinical trials evaluating glucose control. Additional clinical advances are being pursued through an interdisciplinary and collaborative translational project. Participation of the PNR&D in the International Diabetic Neuropathy Consortium (IDNC) is addressing the goals of 1) increasing the understanding of basic mechanisms and risk factors in diabetic neuropathy, 2) improving the detection and understanding of the clinical course of nerve damage in diabetes, and 3) eventually contributing to the prevention and treatment of diabetic neuropathy. The IDNC will ensure an in-depth analysis of basic, epidemiological, and clinical findings of diabetic neuropathy, and in addition provide a unique platform for educating future scientists/clinicians within the field.
In addition, Dr. Eva L. Feldman serves as a Co-Investigator on multiple type 1 diabetes trials, in addition to an ongoing clinical trial assessing an FDA-approved drug commonly used to treat osteoarthritis, to address inflammation – a critical mediator in the development and progression of peripheral nerve damage and pain in diabetes, which has recently been shown to have potential clinical benefit in diabetic neuropathy.