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New Discovery

Brain and central nervous system (Shutterstock)

Brain and central nervous system (Shutterstock)
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Researchers have discovered tiny vessels connecting the brain to the immune system – which could profoundly alter the treatment of autism, Alzheimer’s disease, and multiple sclerosis.
The team at the University of Virginia School of Medicine found the brain – like every other tissue – is connected to the immune system through lymphatic vessels, although these had never been detected despite a thorough mapping of the body.
“I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped,” said Jonathan Kipnis, a neuroscience professor and director of the university’s Center for Brain Immunology and Glia. “I thought that these discoveries ended somewhere around the middle of the last century — but apparently they have not.”
The vessels are “well hidden” along a major blood vessel that travels down into the sinuses, the researchers said, and were discovered only after devising a new way to examine the membrane covering the brain on a single microscope slide.
Antoine Louveau, one of the researchers, noticed vessel-like patterns in the immune cells on his slides, and tests revealed they were lymphatic vessels.
“The first time these guys showed me the basic result, I just said one sentence: ‘They’ll have to change the textbooks,’” said Kevin Lee, chair of the university’s neuroscience department.
The discovery could radically alter the study and treatment of neurological diseases because brain diseases can now be understood mechanically instead of abstractly, researchers said.
“It changes entirely the way we perceive the neuro-immune interaction,” Kipnis said. “We always perceived it before as something esoteric that can’t be studied – but now we can ask mechanistic questions.”
For example, Kipnis said scientists already understand that Alzheimer’s disease is the result of protein accumulations in the brain, but the discovery suggests the lymphatic vessels – which change with age – simply don’t remove them efficiently enough.
The findings have been published in the journal Nature, and the researchers said they could radically alter the way scientists understand the central nervous system’s relationship with the immune system.

Interim Results Reported from Clinical Trial of Stem Cell Transplantation in People with Relapsing-Remitting MS

A nationwide team of researchers report on interim results from a small, five-year study of transplantation of the individuals’ own hematopoietic (blood cell-producing) stem cells combined with high-dose immunotherapy in 24 people with relapsing-remitting MS. This procedure aims at “rebooting” the immune system to prevent MS immune attacks against the brain and spinal cord. At three years, 78.4% of participants experienced no new disease activity. When this trial has completed its five-year duration, it will be an important addition to research needed to determine whether this approach to stem cell transplantation is safe and effective in people with MS. Richard A. Nash, MD (Colorado Blood Center Institute) and colleagues report in JAMA Neurology (Published online December 29, 2014). This study was sponsored by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Background: One type of procedure that has been explored for many years in MS is called “autologous hematopoietic (blood cell-producing) stem cell transplantation” – or HSCT. This procedure has been used in attempts to “reboot” the immune system, which launches attacks on the brain and spinal cord in people with MS.
In HSCT, these stem cells (derived from a person’s own bone marrow or blood) are stored, and the rest of the individual’s immune cells are depleted usually by chemotherapy. Then the stored stem cells are reintroduced back to the individual’s bloodstream. The new stem cells migrate to the bone marrow and over time produce new cells. Eventually they repopulate the body with immune cells. The goal of this currently experimental procedure is that the new immune cells will no longer attack myelin or other brain tissue, providing the person, what is hoped to be, a completely new immune system.
The Study: Investigators enrolled 25 people who had experienced an MS relapse involving loss of neurologic function while taking disease-modifying therapies during the previous 18 months. Participants received HSCT along with high-dose immunosuppressive therapy (a regimen of treatments that profoundly suppress the immune system), and followed for five years. The primary endpoint of this study is whether participants experience “event-free survival,” meaning that they did not die or have an increase in disease activity. Disease activity is defined as any one of the following outcomes occurring: confirmed loss of neurologic function, clinical relapse, or new lesions observed on MRI scans. The current publication presents a planned analysis after three years of follow up.
Results: One individual experienced a pulmonary embolism induced by heparin (administered as part of stem cell collection), and withdrew from the study. Event-free survival at three years was 78.4%, down from 95.8% after one year. Treatment failed in five individuals. Scores on clinical scales measuring disease activity and quality of life, including the EDSS, improved significantly at three years after HSCT. Immune system analysis showed prolonged depletion of the immune cells that drive the immune attack, indicating that the immune system was indeed “rebooted.”
Two deaths occurred, one from complications due to MS progression and another due to asthma. One person experienced an MS attack, an individual who had not complied with a prednisone regimen designed to reduce this risk during collection of stem cells. There were 130 adverse events that were severe or life-threatening, mostly cytopenias (blood cell reductions) and infections.
Comment: Rigorous clinical trials of stem cell therapies are crucial to determining their safety and effectiveness in people with MS. “We look forward to seeing the completed results of this important study,” says Bruce Bebo, PhD, Executive Vice President of Research at the National MS Society. “There are significant risks involved in hematopoietic stem cell transplantation, and it’s important to ensure that this will be a safe solution for people with MS, with significant clinical benefit.”
With the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, the National MS Society believes that the potential of all types of cell therapies must be explored. The Society is currently supporting 15 research projects exploring various types of stem cells, including cells derived from bone marrow, fat and skin, and has supported 70 stem cell studies over the past 10 years.

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