Art+Science participants to talk March 23

Celebrating its third annual “Art+Science” project, the University of Michigan’s A. Alfred Taubman Medical Research Institute will also host two talks featuring the eminent artists and physician-researchers collaborating on the innovative fundraiser.

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Artist Beverly Fishman, left, and Dr. Eva Feldman discuss their work as part of a collaboration for the 2016 Evening of Art+Science.

The Art+Science project connects the institute’s Taubman Scholars – members of the U-M Medical School faculty – with leading contemporary artists, to explore the commonalities in their respective arenas of creativity and discovery. The artists then go on to produce works of art inspired by the lifesaving medical research of their Taubman Scholar partner, and the works are auctioned to fund more medical research grants through the institute.

On March 23 in Bloomfield Hills, Cranbrook Artist-in-Residence Beverly Fishman will take the stage along with PNR&D Director Eva L. Feldman, MD, PhD, at the Cranbrook Art Museum. The duo will discuss their work and the insights they have gained through meetings at one another’s laboratory and studio.

The evening begins at 6 p.m. and the informal talk by Fishman and Feldman will segue into a cocktail reception and possible “sneak peek” of items that will be up for bidding at the gala “Evening of Art+Science” which will take place April 21 at MOCAD in Detroit. Marsha Miro, president of MOCAD, will moderate the discussion.

Another artist-scientist pair will share their art+science experience on March 31 at the U-M Museum of Art (UMMA) in Ann Arbor. The 6 p.m. event will feature a talk with artist Allie McGhee and Taubman Scholar Valerie Opipari, MD, chair of pediatrics and communicable diseases at the U-M Health System. Joe Rosa, director of the UMMA, will chair the discussion.

No registration is required to attend the March 23 and March 31 lecture-receptions.   If you plan to attend, however, kindly e-mail Jason Keech at jkeech@med.umich.edu to facilitate a catering headcount.

For more information about tickets to the April 21 gala and auction, please visit www.TaubmanArtAndScience.org

Dr. Feldman to speak at Lawrence Tech March 29

PNR&D Director Eva Feldman, M.D., Ph.D., has been invited to present her research at 7:30 p.m. on Tuesday, March 29 at Lawrence Technological University in Southfield. The event is part of Lawrence Tech’s Walker L. Cisler Memorial Lecture Series.

Dr. Feldman lecture is titled “Stem Cells in the Treatment of ALS: A New Way Forward,” and will be presented in the Mary E. Marburger Science and Engineering Auditorium (S100) Science Building, Lawrence Technological University. Lawrence Tech is located at 21000 West 10 Mile Road in Southfield.

Dr. Feldman’s lecture will focus on the status of her ground-breaking clinical trial, in which more than 30 ALS patients received injections of stem cells in their spinal cords. Phases 1 and 2 of the trial showed that the procedure is safe and well-tolerated by patients, and 70 percent of those who received the stem cells recovered to levels higher than historic controls. A third phase of the trial is currently being designed.

PNR&D team publishes key Alzheimer’s findings

Scientists in the Program for Neurology Research & Discovery drew one step closer to understanding the benefits stem cells provide in the fight against Alzheimer’s disease, with publication last month of an article in the scientific journal Stem Cells Translational Medicine.

The article was one of five published by PNR&D scientists in January alone.

The Alzheimer’s article, “Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-I: A Novel Cellular Therapy for Alzheimer’s Disease,” e-published January 7, 2016, demonstrated in cell culture models that stem cells expressing a neuroprotective growth factor promote the development of new cells and synapses, enrich the environment for neurons to thrive, and offer improved protection against Alzheimer’s disease insults. The paper also demonstrates that the cells can survive in the brain of a mouse model of Alzheimer’s disease following transplantation, supporting continued testing for effects on learning and memory. The stem-cell line used in the experiment was developed by PNR&D scientists in conjunction with Neuralstem, Inc.

“We believe that injecting stem cells into the brains of diseased mice will have astonishing effects on memory and cognition,” said Eva Feldman, M.D., Ph.D., the study’s principle investigator and Director of the PNR&D. “By digging deeper into properties of these cells, we are now beginning to understand how that will happen and gaining knowledge which will ultimately allow us to apply those lessons to the human brain.”

PNR&D scientists have already advanced stem cell therapies to larger mammals and hope to conduct a human clinical trial on stem cell therapies for Alzheimer’s disease by 2018.

Alzheimer’s disease affects 5.2 million people in the United States, a number that is expected to double by 2050. Alzheimer’s disease is characterized by an accumulation of abnormal proteins in the brain which, over time, injure and kill brain nerve cells.  As the nerve cells are lost, so is a person’s ability to think, reason and function normally.

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PNR&D scientists had a prolific month of publishing, including a review published in the Journal of the American Medical Association, the largest medical journal in the United States:

Electrodiagnostic Tests in Polyneuropathy and Radiculopathy. Callaghan BC, Burke JF, Feldman EL. JAMA. 2016 Jan 19;315(3):297-8. doi: 10.1001/jama.2015.16832.

Program scientists also published these articles in January:

The role of endoplasmic reticulum stress in hippocampal insulin resistance. Sims-Robinson C, Bakeman A, Glasser R, Boggs J, Pacut C, Feldman EL. Experimental Neurology. 2016 Jan 13;277:261-267. doi: 10.1016/j.expneurol.2016.01.007.

Antisense Oligonucleotides for Duchenne Muscular Dystrophy: Why No Neurologist Should Skip This. Jacobson RD, Feldman EL. JAMA Neurology. 2016 Jan 4:1-2. doi: 10.1001/jamaneurol.2015.4011. [Epub ahead of print] No abstract available.

Differential impact of type-1 and type-2 diabetes on control of heart rate in mice. Stables CL, Auerbach DS, Whitesall SE, D’Alecy LG, Feldman EL. Autonomic Neuroscience. 2016 Jan;194:17-25. doi: 10.1016/j.autneu.2015.12.006. Epub 2015 Dec 17.

PNR&D scientists close 2015 on a high note

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:

2015 Feldman Laboratory Publications2

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.

Dr. Hinder highlighted in ‘Neurology Today’

In late September, Lucy M. Hinder, PhD, a postdoctoral fellow in the University of Michigan’s Program for Neurology Research and Discovery, was awarded the 2015 Wolfe Neuropathy Research prize at the American Neurological Association annual meeting. The award is named for a Tennessee businessman, Winston Wolfe, who made his fortune selling safety eyewear and started a foundation to support research on peripheral neuropathy. Dr. Hinder is the first woman and the first scientist without a medical degree to be given this award. In an interview before the meeting, she discussed the events and mentors that helped shape her career.

[Read full story here]

Dr. Feldman presents ALS trial data at conference

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, according to data presented by Dr. Eva Feldman at the American Neurological Association’s 2015 Annual Meeting in Chicago.

Additionally, 70 percent of patients recovered to higher levels than those of the historic control.

“The results of Phase I and Phase II are very encouraging, and we plan to move forward and expand this trial in 2016,” said Dr. Feldman, the Russell N. DeJong Professor of Neurology at the University of Michigan, as well as Director of the Program for Neurology Research & Discovery, Director of the A. Alfred Taubman Medical Research Institute, and Research Director of the University of Michigan Comprehensive ALS Clinic.

The data was collected through Phase I and Phase II of a trial that began in 2010. Phase II included 15 ambulatory patients with ALS. Participants were divided into five dosing cohorts with three patients in each, who received increasing quantities of cells in the cervical (upper) region of the spinal cord, ranging from two million to eight million cells. The fifth cohort received an additional eight million cells in the lumbar (lower) region.

The most common adverse effect of the stem-cell procedure was post-operative pain due to the surgery. One serious adverse event due to the surgical procedure was observed, but was not attributed to the cells themselves. The patient’s motor function was initially weakened, but then recovered to the patient’s ALS baseline.

Dr. Feldman to join prestigious NAM Oct. 18

Eva L. Feldman, M.D., Ph.D., the Russell N. DeJong Professor of Neurology at the Medical School and director of the Program for Neurology Research and Discovery, will be inducted into the National Academy of Medicine during the organization’s Annual Meeting October 17-19 in Washington, D.C.

Dr. Feldman, who is also director of the A. Alfred Taubman Medical Research Institute, is an internationally renowned expert in amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease.  She has devoted her career to finding new therapies and treatments for neurodegenerative diseases, and is at the forefront of applying stem cell research to human disease.

The National Academy of Medicine, founded as the Institute of Medicine, joined the National Academy of Sciences and the National Academy of Engineering in July 2015 as the third academy overseeing the program units of the newly formed National Academies of Sciences, Engineering, and Medicine.

Dr. Feldman earns award for Michigan-Israel bond

PNR&D Director Eva L. Feldman, M.D., Ph.D. will receive the 2015 Chuck Newman Impact Award from the Michigan Israel Business Bridge at the MIBB’s Ambassador Awards dinner on Oct. 14 at The Reserve in Birmingham.

Ticket and sponsorship information for the Ambassador Awards event are available at www.michiganisrael.com.

The award, named for the MIBB’s co-founder, is annually presented to individuals who personify MIBB’s goal of linking Michigan and Israel.

Dr. Feldman has been instrumental in several collaborations among scientists in both countries. In addition, Dr. Feldman serves as an advisor to the United States-Israel Binational Science Foundation, which funds such scientific partnerships.

PNR&D Scientist Honored by American Neurological Association

Group shots and head shots of Dr. Eva Feldman and her lab staff in the BSRB on 10/2/09.

Dr. Hinder

Lucy Hinder, Ph.D., a researcher in the Program for Neurology Research & Discovery, has been awarded the Wolfe Neuropathy Research Prize by the American Neurological Association for her work on the impact of diet on diabetic neuropathy.

Dr. Hinder joined the PNR&D team in 2009. That’s the same year the Wolfe Prize was established by Winston Wolfe and the ANA, to honor outstanding investigators who identify a new cause or treatment of axonal peripheral neuropathy.

The prize is $2,000, and includes complimentary registration at the ANA Annual Meeting, a plaque, and up to $2,000 in travel expenses to present at the event. This year’s ANA meeting will be held Sept. 27-29 in Chicago.

The American Neurological Association is a professional society of academic neurologists and neuroscientists devoted to advancing the goals of academic neurology; to training and educating neurologists and other physicians in the neurologic sciences; and to expanding both our understanding of diseases of the nervous system and our ability to treat them.

Recent PNR&D publications

Scientists at the Program for Neurology Research & Discovery have had four scientific articles accepted by peer-reviewed journals since the beginning of May 2015, including:

Insulin resistance prevents AMPK-induced tau dephosphorylation through Akt-mediated increase in AMPKSer485 phosphorylation, in The Journal of Biological Chemistry. Authors Bhumsoo Kim, Claudia Figueroa-Romero, Crystal Pacut and Eva L. Feldman’s study linked obesity and diabetes with a greater risk of Alzheimer’s disease.

The Metabolic Syndrome and Microvascular Complications in a Murine Model of Type 2 Diabetes, in Diabetes. Authors Junguk Hur, Jacqueline R. Dauch, Lucy M. Hinder, John M. Hayes, Carrie Backus, S Pennathur, Matthias Kretzler MD and Frank C. Brosius, MD. This study demonstrated that small and large nerve fibers are affected by diabetes in different ways and may therefore require different potential therapies for diabetic nerve damage.

The Role of Oxidized Cholesterol in Diabetes-Induced Lysosomal Dysfunction in the Brain, in Molecular Neurobiology. Researchers Catrina Sims-Robinson, Anna Bakeman, Andrew Rosko, Rebecca Glasser, and Eva L. Feldman, MD. Since lysosome dysfunction precedes neurodegeneration, cognitive deficits, and Alzheimer’s disease neuropathology, our results may provide a potential mechanism that links diabetes with complications of the central nervous system.

Amyotrophic lateral sclerosis: mechanisms and therapeutics in the epigenomic era, in Nature Reviews Neurology. Researchers Ximena Paez-Colasante, Ph.D.; Claudia Figueroa-Romero, Stacey A. Sakowski, Stephen A. Goutman, MD; and Eva L. Feldman, MD, PhD, reviewed the latest findings regarding the role of miRNA modifications and other epigenetic mechanisms in ALS, and discussed their potential as therapeutic targets.