Phase I Trial Results of Neural Stem Cell Transplantation Encouraging Those Suffering from Pelizaeus-Merzbacher Disease

Could Also Have Application for Wide Range of Neurological-related Conditions

Newswise — NEW ORLEANS (May 1, 2013) — Research findings offered today during the 81st American Association of Neurological Surgeons (AANS) Annual Scientific Meeting show human central nervous system stem cells (HuCNS-SC) foster myelin formation following HuCNS-SC transplantation.

Pelizaeus-Merzbacher Disease (PMD) is a rare leukodystrophy caused by mutation of the Proteolipid Protein 1 gene, and defective oligodendrocytes in PMD fail to myelinate axons, causing global neurological dysfunction. Researchers undertook this one-year open-label Phase I study to evaluate safety and to detect possible evidence of myelin formation after HuCNS-SC transplantation. Allogeneic HuCNS-SCs were surgically implanted into the frontal lobe white matter in four male subjects with an early-onset severe form of PMD. Immunosuppresion was administered for nine months. Serial neurological evaluations, developmental assessments and cranial MRI and MR spectroscopy (MRS), including high angular resolution diffusion tensor imaging (DTI), were performed at baseline and and following transplantation. The results of this study, Neural Stem Cell Transplantation and Myelination: Results of a Phase I Trial in Pelizaeus-Merzbacher Disease, will be presented by Nalin Gupta, MD, PhD, FAANS, from 11:34-11:45 a.m. on Wednesday, May 1. Co-authors are Roland Henry, PhD; Jonathan Strober, MD; Sang-Mo Kang, MD; Daniel Lim, MD, PhD; Monica Bucci, MD; Eduardo Caverzasi, MD; Laura Gaetano, PhD; Maria Mandelli, PhD; Tamara Ryan, RN; Rachel Perry, RN; Jody Farrell, RN; Rita Jeremy, PhD; Mary Ulman, RN; Stephen Huhn, MD; A. James Barkovich, MD; and David Rowitch, MD, PhD.

The researchers found that the neurosurgical procedure, immunosuppression regimen and HuCNS-SC transplantation were well tolerated. Modest gains in neurological function were observed in three of the four subjects, and no clinical or radiological adverse affects were directly attributed to the donor cells. Reduced T1 and T2 relaxation times were observed in the regions of transplantation nine months post-procedure in three subjects. Normalized DTI showed increasing fractional anisotropy and reduced radial diffusivity, indicating microstructural changes that are consistent with myelination, in the region of transplantation compared to control white matter regions remote to the transplant sites. As a result, the researchers concluded that the Phase I findings indicate a favorable safety profile for HuCNS-SC in subjects with PMD.

“Observing that the transplanted stem cells not only were surviving, but that in three of the four children, the results were consistent with myelination, was extremely encouraging,” said Nalin Gupta, MD, PhD, FAANS. “It gives us a starting point to look at how this knowledge could be applied in other ways. This was the first time, to my knowledge, that we could see evidence of successful cell engraftment. So while we were excited about the prospects of what this could do for someone suffering from PMD, there are large opportunities for this to impact individuals who have suffered from a stroke or traumatic brain injury. The next step would be a Phase II trial, with more patients, the use of more cells and insertion points.”

Disclosure: Nalin Gupta, MD, PhD, FAANS, disclosed that StemCells Inc. provided grant and research support.

Media Representatives: The 2013 AANS Annual Meeting Press Kit includes releases on highlighted scientific research, AANS officer and award winners, National Neurosurgery Awareness Week, and other relevant information about this year’s program. Those releases also will be posted under the Media area on the 2013 AANS Annual Scientific Meeting website (http://www.aans.org/Annual Meeting/2013/Main/Media.aspx). If you have interest in a topic related to neurosurgery or would like to interview a neurosurgeon — either on-site or via telephone — during this year’s event, please contact John Iwanski, AANS Director of Member and Public Outreach, via the onsite press room at (504) 670-4910 or e-mail him at [email protected].

About the 2013 AANS Annual Scientific Meeting: Attended by neurosurgeons, neurosurgical residents, medical students, neuroscience nurses, clinical specialists, physician assistants, allied health professionals and other medical professionals, the AANS Annual Scientific Meeting is the largest gathering of neurosurgeons in the nation, with an emphasis on the field’s latest research and technological advances. A record-breaking 1,003 scientific abstracts were presented for review at the 2013 AANS Annual Scientific Meeting, and the scientific presentations given at this year’s event represent cutting-edge examples of the incredible developments taking place within the field of neurosurgery. Additional information about the AANS Annual Scientific Meeting and the Meeting Program can be found at http://www.aans.org/Annual Meeting/2013/Main/Home.aspx.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with nearly 8,300 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system including the spinal column, spinal cord, brain and peripheral nerves. For more information, visit www.AANS.org.