New Study Finds Blood-Spinal Cord Barrier Compromised In Mice With ALS
Main Category: Neurology / Neuroscience News
Article Date: 20 Nov 2007 - 17:00 PST



The blood-spinal cord barrier is functionally impaired in areas of motor neuron damage in mice modeling amyotrophic lateral sclerosis (ALS), report researchers at the University of South Florida Center for Aging and Brain Repair. The barrier disruption was found in mice at both early and late stages of ALS, a progressive neurodegenerative disease affecting nerve cells in the brain and the spinal cord.

The study, "Evidence of Compromised Blood-Spinal Cord Barrier in Early and Late Symptomatic SOD1 Mice Modeling ALS," appears online in PLoS ONE, an international, peer-reviewed journal published by the Public Library of Science.

The blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) control the exchange of substances between the blood and the central nervous system. These barriers, formed by cells lining the blood vessels in the brain and the spinal cord, protect nerve cells by restricting entry of potentially harmful substances and cells of the immune system. Impairment in cellular machinery of the BBB and BSCB may lead to a barrier breakdown in many brain and spinal cord diseases or injuries.

"We detected vascular leakage in the cervical and lumbar spinal cord microvessels of ALS mice not only at the end-stage of disease but also in those with early disease symptoms," said lead author Svitlana Garbuzova-Davis, PhD, DSc, assistant professor in the USF Center for Aging and Brain Repair. "This may suggest that large molecules such as the antibody IgG and other blood proteins appear in the spinal cord due to vascular leakage, one possible mechanism accelerating motor neuron damage."

However, Dr. Garbuzova-Davis said, questions remain: "Is the BCSB altered before disease symptoms and other pathological processes begin in ALS, and does the protective barrier's breakdown play a primary role in the development of ALS?"

"If this finding translates to ALS patients, then it should yield important ways of developing new treatments that focus on drugs or cell therapies designed to repair the BSCB," said Paul R. Sanberg, PhD, DSc, co-author and director of the USF Center for Aging and Brain Repair.

The research builds upon another USF study published earlier this year in the journal Brain Research. Using electron microscopy to examine the capillary structure of the BBB and BSCB, the researchers demonstrated extracellular edema and physical damage to capillary endothelial cells, motor neurons, and astrocytes surrounding vessels in mice with early and late ALS symptoms.

In the most recent study, the researchers examined the functional competence of the BSCB in ALS mice. They intravenously injected a blue dye tracer into mice in different stages of ALS. Vascular leakage of the dye was found in mice with initial signs of ALS such a tremor, weight loss and reduced hindlimb extension and in mice with complete hindlimb paralysis at the terminal stage of ALS. Furthermore, the study found decreased expression of the glucose transporter Glut-1 and immunological markers CD146 for endothelial cells and GFAP for astrocytes, which may relate to vascular leakage.

The USF researchers plan to investigate whether the BSCB and BBB are altered in patients suffering from ALS. Other USF authors of the PLoS ONE study were Samuel Saporta, PhD, Edward Haller, Irina Kolomey, MD, Steven Bennett, and Huntington Potter, PhD, CEO of the Byrd Alzheimer's Research Center.

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida's colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With $308 million in research funding last year, USF is one of the nation's top 63 public research universities and one of Florida's top three research universities.

Citation: Garbuzova-Davis S, Saporta S, Haller E, Kolomey I, Bennett SP, et al (2007) Evidence of Compromised Blood-Spinal Cord Barrier in Early and Late Symptomatic SOD1 Mice Modeling ALS. PLoS ONE 2(11): e1205.
doi:10.1371/journal.pone.0001205
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Neuralstem Obtains UCSD Stem Cell Delivery System for Use in Spinal Cord Trials

November 20, 2007: 08:00 AM EST


ROCKVILLE, Md., Nov. 20 /PRNewswire-FirstCall/ -- Stem cell company, Neuralstem, Inc. , today announced that it has exclusively licensed the "Spinal Multisegmental Cell and Drug Delivery System," invented by Dr. Martin Marsala at the University of California, San Diego (UCSD). The exclusive, worldwide license to Neuralstem covers all fields of use and includes the right to grant sublicenses. Under the terms of the agreement, UCSD will be eligible for milestone payments and royalties and Neuralstem will assume the cost of development, manufacture and approval of the product.

(Logo: http://www.newscom.com/cgi-bin/prnh/...21/DCTH007LOGO )

"Neuralstem is actively pursuing human clinical trials for its human spinal cord stem cells to treat Ischemic Paraplegia, ALS and Traumatic Spinal Cord Injury," said Neuralstem CEO Richard Garr. "All three indications require delivering our cells directly into the spinal cord. We believe that Dr. Marsala's injection device will allow for a minimally invasive injection of the cells into the spinal cord, thus significantly reducing the risk of the surgery to any patients receiving cell or drug therapy administered directly into the spinal cord."

"The device provides a unique method for delivering cells horizontally along the length of the spinal cord," said Dr. Marsala, "which will reduce the number of entry sites needed for therapeutic intervention. We believe that this will greatly enhance the likelihood of success for treating many indications." Dr. Marsala went on to say, "Neuralstem has not only shown a strong commitment to moving their spinal cord stem cells into the clinic, but to creating a therapy that can be broadly and safely delivered. We are excited to have them as our exclusive licensee for this important technology."

About Neuralstem

Neuralstem's patent-protected technology enables, for the first time, the ability to produce neural stem cells of the human brain and spinal cord in commercial quantities, and the ability to control the differentiation of these cells into mature, physiologically relevant human neurons and glia. The Company expects that its first Investigational New Drug (IND) application will be for the treatment of Ischemic Paraplegia, a form of paraplegia that sometimes results from the surgery to repair aortic aneurysms and for which there is no effective treatment. The Company anticipates it will submit its initial IND application to the FDA during calendar year 2007.

Major Central Nervous System diseases targeted by the Company with research programs currently underway include: Ischemic Paraplegia, Traumatic Spinal Cord Injury, ALS, and Parkinson's disease. The company's cells recently extended the life of rats with ALS (Lou Gehrig's disease) in a paper published in the journal TRANSPLANTATION, and were deemed viable for continued work in neurodegenerative spinal conditions. Neuralstem cells also reversed paralysis in rats with Ischemic Spastic Paraplegia, a form of paralysis that can result from the surgery to repair aortic aneurysms, as reported in NEUROSCIENCE (http://www.neuroscienceibro.com/). The company has also developed immortalized human neural stem cells for in-vitro use in drug development for the academic and pharmaceutical markets. For further information, please visit http://www.neuralstem.com.

Cautionary Statement Regarding Forward Looking Information

This press release may contain forward-looking information about Neuralstem, Inc., which are intended to be covered by the safe harbor for forward-looking statements provided by the Private Securities Litigation Reform Act of 1995. Forward- looking statements are statements that are not historical facts. These statements can be identified by the use of forward- looking terminology such as "believe," "expect," "may," "will," "should," "project," "plan," "seek," "intend," or "anticipate" or the negative thereof or comparable terminology, and include discussions of strategy, and statements about industry trends and Neuralstem's future performance, operations and products. This and other "Risk Factors" contained in Neuralstem's public filings with the SEC should be read in connection with this release. For further information on Neuralstem, please review the company's filings with the SEC including periodic reports, including the quarterly report on Form 10- Q for the quarter ended September 30, 2007.

http://money.cnn.com/news/newsfeeds/...20112007-1.htm