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.
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.
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.
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.
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.
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.
Eight researchers from the Program for Neurology Research & Discovery attended the Peripheral Nerve Society’s 2015 meeting, held June 28-July 2 in Quebec.
Postdoctoral Fellows Philippe O’Brian, Lucy Hinder and Amy Rumora presented posters. Also in attendance from PNRD&D were director Eva L. Feldman, M.D., Ph.D.; Brian C. Callaghan, M.D.; Samy Kashlan, John Hayes and Jacque Dauch.
Posters presented included:
‘Effect of Dietary Reversal on Peripheral Nerve Function in a Mouse Model of Pre-Diabetes’
Presentation I: ‘High-fat Diet-induced Metabolic Neuropathy: Effect of Mouse Strain’
Presentation II: ‘Shared Transcriptional Networks Between Diabetic Peripheral Neuropathy in Murine Models of Diabetes’
Presentation I: ‘Hyperlipidemia Alters Mitochondrial Trafficking in Dorsal Root Ganglion Sensory Neurons’
Presentation II: ‘Identification of a Tissue-Specific Effect of Pioglitazone Treatment on Gene Expression Profiles in a Murine Model of Type 2 Diabetes’
Brian C. Callaghan, M.D.:
‘The Association of Metabolic Syndrome Components with Polyneuropathy in an Obese Population’
Four scientists from the Program for Neurology Research & Discovery presented their work at the 2015 American Diabetes Association’s Scientific Sessions, held June 5-9 in Boston.
In addition, two former PNR&D researchers presented at the meeting.
“The ADA is an excellent opportunity for our researchers to present their remarkable work,” said PNR&D Director Eva Feldman, M.D., Ph.D. “In one session we had three of the six speakers. It was good day for the program and our science.”
The papers presented by PNR&D scientists at the ADA meeting included:
- Rodica Pop-Busui: “Cardiovascular Autonomic Neuropathy in Pima Indians with Diabetic Kidney Disease (DKD)
- Rodica Pop-Busui: “Cardiovascular Autonomic Neuropathy and Coronary Artery Calcium in Type 1 Diabetes: The CACTI Study”
- Meeyoung Park: “Identification of a Tissue-specific Effect of Pioglitazone Treatment on Gene Expression Profiles in a Murine Model of Type 2 Diabetes”
- Phillipe O’Brien: “Effect of Dietary Reversal on Peripheral Nerve Function in Prediabetic C57BL6 Mice”
- Mamta Jaiswal: “Burden of Diabetic Peripheral Neuropathy among Pima Indians”
Scientists presenting who previously worked at PNR&D included:
- Junguk Hur, Ph.D.: “Shared Transcriptional Networks between Diabetic Peripheral Neuropathy and Nephropathy in Murine Models of Diabetes”
- Tatsu Himeno – “Decrease of Neuronal Progenitor/Stem Cells in Dorsal Root Ganglia of Diabetic Mice”
The scientists of the Program for Neurology Research and Discovery pay tribute to our generous benefactor, A. Alfred Taubman, whose vision and generosity have paved the way for new discoveries aimed at alleviating the suffering of millions.
Mr. Taubman has long supported the research mission of the Program, which is focused on translating laboratory discoveries into new patient therapies for such devastating diseases as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and the nerve complications of diabetes.
Thank you, Mr. Taubman. You will be missed, but your vision lives on.
The Program for Neurology Research & Discovery will receive $1.2 million over six years from the Norvo Nordisk Foundation, as part of a larger study to understand diabetic neuropathy in American and European populations.
The funds are part of an overall grant of 60 million Danish Kroner ($9 million) that will establish the International Diabetic Neuropathy Consortium (IDNC) of researchers in the U.S., Denmark and England. Diabetic neuropathy afflicts about half of diabetes patients. It is characterized by extreme pain in the feet, and is one of the leading causes of diabetes-related hospital admissions and amputations.
Researchers from the University of Michigan, the Odense University Hospital in Denmark, and Oxford University in the United Kingdom will work together on the study, the largest ever to investigate the mechanisms of diabetic neuropathy, or nerve pain. The grant’s lead investigator is Troels Jensen, a Clinical Professor in the Department of Clinical Medicine at Aarhus University.
“We are so fortunate to receive funding for this important work,” said PNR&D Director Eva L. Feldman, M.D., Ph.D. “Diabetes has reached epidemic levels in the United States and Europe, and by combining the brainpower and resources of these three major research institutions, we have a real chance of getting to the bottom of this excruciating condition that affects so many diabetes patients. We’re thankful to Novo Nordisk and Dr. Jensen for this opportunity.”
Dr. Feldman will travel to Denmark in May 2015 to help launch the IDNC initiative.
It is estimated that 26 million Americans and 60 million Europeans suffer from diabetes, and both numbers are expected to climb in the coming years.
Researchers hope to combine data from clinical studies, basic research and registry studies, so they can eventually assess an individual patient’s risk of developing diabetic neuropathy. Such early detection will allow physicians to treat the affliction more effectively.
Researchers in Dr. Feldman’s lab are focused on the following:
· Understanding how changes in blood glucose and lipids (blood fats) that result during diabetes damage nerves.
· Using nerve cells grown in a petri dish and treated with high glucose and lipids to discover new drugs to treat nerve damage.
· Determining the changes in DNA, RNA and protein from nerves in animals and patients affected with diabetes to uncover the cause of nerve damage. This will point the way to new treatments to protect and nourish the nerves under attack.
· PNR&D researchers are also studying the relationship of obesity, insulin resistance and Alzheimer’s disease, and links between diabetes and dementia.
The Novo Nordisk Foundation gave DKK240 in 2014 for four separate studies on the prevention of diabetes and obesity, and the complications of diabetes.