Success of ALS clinical trial builds promise for neural stem cell therapies

Ann Arbor, Mich. — Patients with amyotrophic lateral sclerosis (ALS) who received cervical intraspinal injections of neural stem cells tolerated the procedure well and showed no signs of accelerated disease progression, a finding that lays critical groundwork for the use of neural stem cells in treating degenerative neurological disorders like ALS, or Lou Gehrig’s disease, and other neurodegenerative disorders.

Results of the first-of-its kind clinical trial led by researchers at the University of Michigan, “Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: Phase 1 trial outcomes,” will be published in the March 2014 edition of Annals of Neurology.

The research team led by Eva Feldman, M.D., Ph.D., used a novel spinal-mounted stabilization and injection device to deliver up to 1.5 million neural stem cells to the cervical, or upper, spinal cord of six ALS patients in the study’s second cohort. The first cohort included 12 patients who received stem-cell injections in the lumbar, or lower, spinal cord. Three patients were in both cohorts and received both treatments.

The Phase 1 trial is the first ever to use human subjects to test the safety of intraspinal stem cell injections. A Phase 2 trial is under way at the University of Michigan, Emory University and Massachusetts General Hospital to determine how patients do with larger doses. In Phase 2, subjects will receive as many as 16 million stem cells in the 9-hour procedure.

“We are extremely excited by the findings of this clinical trial,” said Dr. Feldman, Director of the A. Alfred Taubman Medical Research Institute, Director of Research for the ALS Clinic at the University of Michigan Health System, principle investigator for the trial and lead author. “If we can show that injecting these stem cells can slow or even halt the progress of this devastating disease, we can begin to pursue further therapies and trials in the promising area of regenerative medicine.”

Researchers are hopeful that the lessons learned from the ALS stem-cell trial will help inform efforts to treat other serious neurological disorders, including Alzheimer’s disease and multiple sclerosis.

That concept is echoed in a commentary piece also to be published in the March 2014 edition of the Annals of Neurology titled “Cell therapy in amyotrophic lateral sclerosis: A significant step forward,” by Tamir Ben-Hur, M.D., Ph.D., of Hadassah University Hospital in Israel. In the article, Dr. Ben-Hur noted that the ALS study not only established a technical benchmark for stem-cell injections, but also breaks a critical psychological barrier to stem-cell therapies.

“The importance of this report … lies far beyond its immediate conclusions,” Dr. Ben-Hur wrote. “The special design of the present study sets new standards for further clinical translation in regenerative medicine for neurological diseases.”

The stem cells for Phase 1 and Phase 2 clinical trials were developed by Neuralstem, Inc., a company whose patented technology enables the production of neural stem cells of the brain and spinal cord in commercial quantities, and the ability to control the differentiation of these cells constitutively into mature, physiologically relevant human neurons and glial cells. Neuralstem, Inc. is a publicly traded company based in Rockville, Md. Dr. Feldman is an unpaid consultant to Neuralstem, Inc.

11 Taubman Scholars named among America’s best doctors

The following Taubman Scholars and Emerging Scholars are among the University of Michigan Medical School physicians recently named to the 2013-2014 “Best Doctors In America” list.

Frank (Chip) Brosius III, M.D.

Valerie P. Castle, M.D.

Sung Won Choi, M.D.

Eva L. Feldman, M.D., Ph.D.

Thomas W. Gardner, M.D., M.S.

Johann Gudjonsson, M.D., Ph.D.

Alon Kahana, M.D., Ph.D.

Theodore S. Lawrence, M.D., Ph.D.

Parag Patil, M.D., Ph.D.

Henry L. Paulson, M.D.

Max S. Wicha, M.D.

The new national list includes 493 U-M physicians — and places them among the best 5 percent of doctors in their specialties. UMHS has more physicians recognized than any other health system in Michigan.

The list is compiled every year by Boston-based Best Doctors, Inc., and based on an in-depth survey, the List contains more than 53,000 U.S. physicians in 40 specialties and more than 400 subspecialties of medicine. In a confidential review, current physician listees answer the question, “If you or a loved one needed a doctor in your specialty, to whom would you refer?”

This yields a preliminary set of doctors who meet the initial criteria for inclusion. These physicians are then checked for credentials, disciplinary actions and clinical activity. Only doctors who meet all evaluation criteria are selected for the list.

A full list of the UMHS doctors on this year’s list is available at http://umhealth.me/bestdoc14.

Dr. Feldman paired with artist in ‘Art and Science’ fundraiser

 

Detroit artist John Corbin (left) visited the lab of Eva Feldman, M.D., Ph.D., on March 20, 2014.

Detroit artist John Corbin (left) visited the lab of Eva Feldman, M.D., Ph.D., on March 20, 2014.

Detroit — Dr. Eva Feldman, Director of the Program for Neurology Research & Discovery, will be paired with multimedia artist John Corbin of Detroit in a unique fundraising event, An Evening of Art and Science, on May 22 at the Museum of Contemporary Art Detroit.

The event will unveil the works inspired by the pairing of 11 physician-researchers of the A. Alfred Taubman Medical Research Institute with noted artists from the Detroit area and beyond. For months, the artists have been meeting with their medical counterparts to discuss the creativity that abounds in their respective disciplines, and to gain ideas and inspiration from the medical research being conducted by these dedicated clinician-scientists from the University of Michigan.

The art pieces generated from those collaborations will be sold at auction and the proceeds used to fund the Taubman Emerging Scholars program, which helps early-career clinician-scientists establish their laboratories.

For more information on the event, click here.

Taubman, Feldman receive ALSA Michigan Legacy of Hope Award

The ALS Association Michigan Chapter has named Mr. A. Alfred Taubman, founder and chair of the A. Alfred Taubman Medical Research Institute, and Eva L. Feldman, M.D., Ph.D., the institute’s director, as the 2014 recipients of the association’s Legacy of Hope Award.

The award honors individuals who effect positive changes within the ALS community and demonstrate a remarkable commitment to the betterment of treatment for ALS patients, and the research necessary to find the cure for ALS.

“We are delighted to create this event to celebrate extraordinary individuals. Dr. Eva Feldman and Mr. A. Alfred Taubman have been selected to receive the Legacy of Hope award because of their dedication and commitment to the ALS community,” said Paula Morning, executive director of the association.

Through his establishment of the Taubman Institute at the University of Michigan, as well as for his philanthropic support of Dr. Feldman’s laboratory, the Program for Neurology Research & Discovery, Mr. Taubman has created an environment where scientists are working on ALS-related research ranging from imaging techniques to provide early diagnosis, to Dr. Feldman’s landmark trial of a first-ever stem cell treatment for ALS.  To date, 22 patients have received injections of specially engineered stem cells directly to their spinal cords in the FDA-approved trial, which is testing the ability of the stem cells to replace dying motor neurons.

“Mr. Taubman and I are deeply grateful to be selected as the inaugural recipients of this honor,” said Dr. Feldman.  “We greatly appreciate the recognition of our work at the Taubman Institute to create hope for ALS patients and their families, and are proud to accept it as representatives of the many other researchers, philanthropists and caregivers striving every day in the quest for new cures and treatments.”

Dr. Feldman and Mr. Taubman will be honored at the Legacy of Hope evening sponsored by the ALS Association Michigan Chapter on April 3.  The black-tie gala featuring a reception, dinner, auction and awards program will be held at the Townsend Hotel in Birmingham beginning at 6 p.m.   For information about tickets and sponsorship opportunities, visit www.alsa-michigan.org or call (248) 680-6540.

Journal recognizes Hinder paper as one of 2013′s best

A paper by PNR&D postdoctoral fellow Lucy Hinder, Ph.D., was recently named one of 2013’s best by editors of Journal of Endocrinology.

The paper, ‘Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes,’ was published in Journal of Endocrinology January 2013.

The journal’s best papers were assessed using a number of factors, including the opinion of the Editorial Board and usage.

Click here to read the abstract.

Dual MRI technique leads to more accurate ALS diagnosis

A technique that uses two different types of magnetic resonance imaging (MRI) on the brain can more accurately diagnose amyotrophic lateral sclerosis  (ALS) than using a single type of MRI alone, a finding that could lead to earlier diagnoses of the deadly disease and ultimately to more effective treatments for patients. (Watch video here)

The study, “Multi-modal MRI as a Diagnostic Biomarker for Amyotrophic Lateral Sclerosis,” was performed by a research team from the University of Michigan’s Program for Neurology Research & Discovery, led by University of Michigan neuro-radiologist Bradley R. Foerster, M.D., Ph.D., an Emerging Scholar in the A. Alfred Taubman Medical research Institute.

Dr. FoersterThe article was published in the open-access Annals of Clinical and Translational Neurology, an official journal of the American Neurological Association.

The diagnosis of ALS, also known as Lou Gehrig’s Disease, is challenging to physicians because different patients show a wide range of symptoms. By adding proton magnetic resonance spectroscopy to diffusion tensor imaging, researchers found that diagnostic accuracy was significantly improved over that of DTI alone. Researchers hope that multi-modal MRI can help them identify biomarkers specific to ALS, and in earlier stages of the disease.

“We’re going to enroll patients with earlier-onset disease,” Dr. Foerster said. “And then we’re also going to include patients with other types of disease to make sure we have a signature that’s specific. What we’re trying to do is create an imaging fingerprint of this disease, just like you have a fingerprint that’s unique to you.”

In the study, Foerster and his team compared 29 ALS patients with 30 age- and gender-matched healthy controls. The subjects underwent brain MRI that collected thousands of data points, which Foerster and his colleagues will use to identify imaging characteristics of patients with early ALS.

“Analyzing this data is quite challenging,” Dr. Foerster said. “We’re trying to hone down the statistical models to say ‘what are the definitive characteristics of this imaging set for these disease patients?’”

ALS is a debilitating motor neuron disease that causes the loss of nerve cells in the brainstem and spinal cord that control movement. Also known as Lou Gehrig’s disease, it usually strikes people in midlife and is relentlessly progressive, typically resulting in death within five years of the first sign of symptoms. Patients lose the ability to control their limbs, facial muscles, swallowing, and eventually, the ability to breathe. While the causes of ALS are largely unknown, most cases likely arise through a combination of genetic factors and environmental stress.

Cross-discipline research can help researchers expand their understanding of disease mechanisms and treatment, according to Eva Feldman, M.D., Ph.D., Director of the Program for Neurology Research & Discovery and the A. Alfred Taubman Medical Research Institute, both at the University of Michigan.

“These types of collaborations are extremely important to the work we’re doing in our lab and in the Taubman Institute,” Dr. Feldman said. “By working with researchers in other areas, like Dr. Foerster, we can really expand the scope of our discovery. And that ultimately leads us more quickly to more effective treatments for patients of neurologic diseases like ALS.”

The Program for Neurology Research & Discovery (PNR&D) is the laboratory of Dr. Eva Feldman, M.D., Ph.D., the Russell N. DeJong Professor of Neurology at the University of Michigan Medical School and the director of the A. Alfred Taubman Medical Research Institute. Under Dr. Feldman’s direction, the PNR&D’s 30-plus scientists, clinicians, and students are working toward the common aim of understanding and curing neurological diseases.

Dr. Feldman is the principal investigator for a national phase 2 clinical trial that has injected millions of stem cells into the spinal cords of seven ALS patients in an effort to slow or stop the progression of ALS.

Foerster’s research is in part supported by an Emerging Scholar Grant from the A. Alfred Taubman Medical Research Institute.  Emerging Scholar grants are intended to help  junior clinician-scientists at the University of Michigan make progress in their medical research while establishing the credentials required to obtain funding from more traditional sources.

Feb. 5 Health Science Lecture Postponed

The Feb. 5 Health Science Lecture that was scheduled to be delivered by Steven L. Kunkel, Ph.D., the senior associate dean for research at the University of Michigan Medical School, was postponed due to inclement weather. The new date for Dr. Kunkel’s lecture will be posted here as soon as it is scheduled.

About the lecture series: The Health Science Lecture Series is sponsored by the A. Alfred Taubman Medical Research Institute, the Program in Biology and a number of student organizations. The lectures are held quarterly on the U-M campus and focus on a wide variety of topics including medical research, public health, bioethics, evolutionary biology, epidemiology and many others.

The next event is scheduled for March 22, with Parag Patil, M.D., Ph.D., the U-M Medical School neurosurgeon who is performing the intraspinal stem cell injections for ALS patients participating in Dr. Eva Feldman’s landmark trial of a stem cell therapy for that disease.

ALS stem cell trial reaches milestone: 25th stem cell injection

ANN ARBOR, Mich. — A patient with amyotrophic lateral sclerosis (ALS) received six million stem cells injected to the spinal cord in a procedure Jan. 8 at the University of Michigan Health System – the 25th time an ALS patient has undergone the experimental injections as part of a national clinical trial.

The 66-year-old man has returned home and will receive follow-up monitoring and testing to help U-M neurologists assess the safety and any potential effect of the injections. He is the 7th patient to undergo the surgery in Phase 2 of the trial, which began in September and follows a 15-patient Phase 1 trial that produced no adverse side effects in patients undergoing the surgery.

Eva L. Feldman, M.D., Ph.D., the Russell N. DeJong Professor of Neurology at the U-M Medical School and director of the A. Alfred Taubman Medical Research Institute, is the principal investigator for the trial. Feldman has led the analysis of results from the Phase 1 trial which concluded in 2012.

In Phase 1, three of the 15 patients received a second injection of stem cells, for a total of 18 surgeries in that segment of the trial.  The seven surgeries so far in Phase 2 bring the total number to 25.

“We’re pleased that as we reach this important milestone, none of our patients in either phase of the trial have experienced any adverse side effects as a result of the stem cell implantation,” said Feldman.  “We are very excited to note that escalating the number of stem cells per patient does not appear to increase that risk.”

In data presented in 2013, spinal cord injections of between 500,000 to 1.5 million cells were delivered safely and tolerated well in a Phase 1 trial conducted at Emory. The researchers reported possible signs that in one subgroup of participants who received the highest dose of stem cells, ALS progression may have been interrupted.

Additional patients with the condition, also known as Lou Gehrig’s disease, are being evaluated for possible participation in the trial at U-M and Emory University. Patients in the Phase 2 trial will receive up to 16 million of the specially engineered stem cells.

The Phase II trial is approved by the U.S. Food and Drug Administration and funded by Neuralstem, Inc., the Maryland-based company whose stem-cell product the trial is testing. It seeks to study any effect that injected stem cells might have on motor neurons – muscle-controlling nerve cells that die in ALS patients, eventually robbing them of the ability to walk, speak and breathe.

Parag Patil, M.D., Ph.D., a U-M neurosurgeon and biomedical engineer, performed the four operations that have been completed at U-M. In each case, the patient’s spinal column was unroofed and the spinal cord exposed to receive the cells. The cells are introduced via a custom-designed delivery device that is affixed to the subject’s spinal bones so that it moves with the patient’s breathing throughout the process.

Patil, an assistant professor in U-M’s departments of Neurosurgery, Neurology, Biomedical Engineering and Anesthesiology, and a Young Friends of the Taubman Institute Emerging Scholar, also serves as a paid engineering consultant to Neuralstem to further develop the cell-delivery device.

This Phase 2 dose escalation trial is designed to treat up to 15 ambulatory patients in five different dosing cohorts, under an accelerated dosing and treatment schedule.

The first 12 patients, divided into four cohorts, will receive injections only in the cervical region of the spinal cord, where breathing function is controlled. The first cohort of three patients received 10 cervical region injections of 200,000 cells per injection. The second cohort of three patients received 20 cervical region injections of 200,000 cells per injection. The trial has now progressed to the third cohort of three patients receiving 20 cervical injections of 300,000 cells per injection.  If this proves safe, the fourth cohort will receive 400,000 stem cells per injection with  20 cervical injections.

The last three Phase 2 patients will receive injections in both the cervical and the lumbar spinal regions.  These patients will receive 20 injections of 400,000 cells each in the lumbar region in addition to the 20 injections they will already have received in their cervical region.

The trial also accelerates the treatment schedule, and is designed to progress at the rate of one cohort per month with one month observation periods between cohorts. Researchers expect all of the patients could be treated by the end of the second quarter in 2014.

Patients seeking information on the trial should contact the relevant center. For the University of Michigan Health System, please visit: http://www.umclinicalstudies.org/HUM00072488. For Emory Healthcare, please call (404) 778-7777.

For more information on ALS treatment and research at the U-M Health System, visit http://umhealth.me/UM-ALS .

Generous donors fund institute’s summer interns

TaubmanSummerInternsPhilanthropy fuels the Taubman Institute’s mission of funding talented, proven clinician-scientists at U-M, and their promising junior counterparts, through grant programs that support these physicians’ laboratory research.

And now, generous donors have made it possible to teach and encourage the medical science leaders of tomorrow.  Michigan philanthropists Joel and Shelley Tauber, longtime U-M supporters and members of the Taubman Institute’s Leadership Advisory Board, are the benefactors of the institute’s newest initiative, the Tauber Family Student Internship Program.

This five-year financial commitment will finance three student internships each year, allowing undergraduate students to work within the laboratories of Taubman Scholars or Emerging Scholars.  It’s hoped that the exposure to cutting-edge translational medical research will encourage these budding scientists to choose a lifetime of striving to bring new cures and treatments to patients with difficult diseases.

“When young, imagining a future for oneself can be overwhelming,” the Taubers said.  “We want to be part of inspiring young people to pursue a future in medical research by exposing them to Michigan’s scientific environment.

“Our goal is to enable interested and qualified young students to be part of teams that are focused on understanding and advancing medicine and its ability to treat disease.”

For 2013, three students will assist in the Program for Neurology Research & Discovery, the laboratory of Taubman Institute Director Dr. Eva Feldman.  They are:

  • Anna Bakeman, a student at the Medical College of Wisconsin
  • Rebecca Glasser, a student at Harvard University
  • Sangri Kim, a student at Johns Hopkins University

All of the interns will have an opportunity to work on projects ranging from stem cell derivation to the analysis of skin samples taken from neurology patients.

Rebecca Glasser, a West Bloomfield, Mich. native and a sophomore studying molecular and cellular biology at Harvard, says the internship meshes with her career aspiration to work as a clinician-scientist.

Working in the lab is a manifestation of everything I’ve learned in school,” she said.  “It’s great to actually see how everything comes together in the lab, rather than just in a textbook.  It’s really given me perspective on what I want to do.

Crain’s: Man who received ALS stem cell transplant still doing well

TedHaradaTed Harada, a 40-year-old man diagnosed with ALS, who received stem cell implantations to his spinal cord in two separate surgeries as part of the first-ever FDA-approved trial of a stem cell therapy for ALS, talked last week with Crain’s Detroit business reporter Tom Henderson.  Harada said he’s still feeling the positive effects he attributes to his second surgery, which took place last August.

“I’ve been doing great and feeling great.” Harada told Henderson. “Just now, the left leg showed a little bit of weakness returning, but I’m still so much better than I was before the surgeries. It’s the first time, since August, they’ve noticed any slight weakness.

“It’s clear from the data that the injections reversed my symptoms and slowed down the progression of the disease. I’ve received a blessing. I almost forget I have ALS. I don’t have the constant reminder of having to use the canes. Now, I don’t think about ALS every day. Every couple of days something happens and I think, `Oh, yeah, I have ALS.’ ”

Taubman Institute Director Dr. Eva Feldman received FDA approval in April to move the trial to Phase II, which will study efficacy as well as safety.  Patient recruitment has not yet started for that phase of the trial.

Click here to read the entire Crain’s blog post.