The Myelin Project Articles RSS Feed

[firstname] [lastname], The Myelin Project Newsletter 18-Dec-09

Candace Root — Fri, 18 Dec 2009 17:50:47 GMT

[menu]

Hello [firstname],

HAPPY HOLIDAYS

It is that time again, time to look back over 2009 and see where we have been and where we are going. Happy 20th Anniversary to the Myelin Project. It was twenty years ago that Augusto and Michaela Odone created The Myelin Project. When their son, Lorenzo, was diagnosed with adrenoleukodystrophy, they were told that nothing could be done. They were told to take him home and wait for him to die. They would not accept that prognosis and so their journey began and they created The Myelin Project.

We are still racing the clock . The single biggest barrier to progress is our scientific research is lack of funding. Won’t you
please help us today with your generous and immediate support. All donations are fully tax deductible.

You may donate online at http://www.myelin.org/en/donations/add.asp

RESEARCH PROGRESS

In the past twenty years, thanks in part to those who have made generous donations to The Myelin Project, we have learned quite a lot about X-linked ALD (X-ALD). While there are still no therapies available to treat the full-blown symptoms of childhood X-ALD, we have found that, if begun before symptoms develop, treatment with Lorenzo’s oil may be able to prevent the onset of symptoms (Arch Neurol. 2005 62:1073-80). Lorenzo’s oil is not always effective. However, if symptoms are detected very early it is possible to perform a bone marrow or cord blood transplant. When successful, this therapy appears to arrest the development of further symptoms. The first successful transplant recipients are just now entering their 20’s, so that it will still be a few years before we know whether they will also escape AMN.

Last month, a great advance in X-ALD treatment was announced. A team headed by Dr. Patrick Aubourg, University Paris-Descartes, have developed a way to transplant the X-ALD gene (Science. 2009 326:818-23). The team was able to remove most of the genes from a virus, and then replace the viral genes with a normal X-ALD gene. The virus retained its ability to get into cells, but lost its ability to cause any disease. The team then took bone marrow cells from an X-ALD patient, and infected them with the modified virus. The virus carried the normal X-ALD gene into the cell, where it began to function. The modified bone marrow cells were given back to the patient. Because they function normally, the modified bone marrow cells were able to restore gene function in the X-ALD patients. This technique will permit treatment of patients for whom a bone marrow donor is unavailable. Even better, because the patient’s own cells are used, the danger of transplant failure is greatly reduced.

Each of these effective treatments relies on identifying carriers of the X-ALD gene very early. Usually, that does not happen unless another family member has been identified. We are working to help change that. Researchers at The Kennedy Krieger Institute of Johns Hopkins University in Baltimore are developing a newborn screening test for the X-ALD gene. When finished, it is anticipated that the test will be widely adopted. Developing this test is important not only because successful treatment relies on early identification, but also because a significant number (perhaps as high as 5%) of X-ALD cases arise from new gene mutations. In those cases, family history is not helpful in identifying at-risk children.

FUND RAISING

The 2009 Got The Nerve? Triathlon held in Mount Gretna, Pennsylvania was a huge success this year with over 675 participants. The Myelin Project would like to thank Chris Kaag, his immediate and extended family, and the over 100 volunteers for all their hard work and efforts put into this well-organized event. Each year this triathlon gets bigger and better. The Myelin Project would also like to thank Got The Nerve? corporate sponsors: Clover Farms, Yuengling Brewery, PRL. Inc, Reading Orthodontic Group, Power Bar, and All Risks. The 2009 Got The Nerve? Triathlon raised over $20,000 for The Myelin Project. The funds raised at this year’s event have been designated to help fund The Augusto Odone New Investigator Award for AMN research.

The Myelin Project would like to express its sincere and deep gratitude to the people of Branford, Connecticut and the surrounding communities who made the 2009 Hammerfest Triathlon a huge success. The 2009 Hammerfest and Brian’s Beachside Boogie raised over $60,000 for The Myelin Project. These funds have been designated to help fund newborn screening for x-linked ALD.

Thank you to the staff of The Owenego Inn, and Jane Rosenthal, John and Pat Bloomquist for hosting the event each year. We also want to thank Race Productions and Race Director, Ron Meneo, together with Michael, Scott and Margit of Race Productions who produce and direct the Hammerfest Triathlon and Brian’s Beachside Boogie each year. In addition to their services, Race Productions also makes a generous financial donation to The Myelin Project each year. Thank you, Race Productions. A special thank you to Molly Phalen, who donated her 16^th birthday to raise money for The Myelin Project and raised over $3,000. The Myelin Project would also like to take this opportunity to thank John, Jean and Brian Kelley, their immediate and extended family for their generous and continued support.

We also want to acknowledge the fabulous Lemonade Gang of Branford, CT. This group of young people have raised money and donated selflessly to The Myelin Project. The Lemonade Gang was founded by Greg Nobile and Ryan Bloomquist. The Lemonade Gang began approximately eight years ago. The then very young children wanted to do something to help their dear friend, Brian Kelley, in his heroic fight against adrenoleukodystrophy. The gang has evolved but the core group has stayed intact. While their passion has grown, so too has their committment to the Myelin Project. The Lemonade Gang donated over $6,000 to The Myelin Project this year.

THE AUGUSTO ODONE NEW INVESTIGATOR AWARD

This year The Myelin Project created The Augusto Odone New Investigator Award for AMN (adrenomyeloneuropathy) research. This research award is a collaborative effort with Oliver’s Army and is also co-funded by Oliver’s Army. This research award was created to discover ways to treat adrenomyeloneuropathy (AMN), the forgotten side of X-ALD and also to encourage and keep brilliant, promising young scientists interested in leukodsytrophy research and more specifically AMN research.

Approximately one-third of the males who carry the X-ALD gene develop an inflammatory brain disease in childhood, as was depicted in the movie “Lorenzo’s Oil”. But the men who escape this childhood catastrophe almost invariably develop a different disease in their 20’s or 30’s, adrenomyeloneuropathy (AMN). Even fewer know that about half of women who carry the X-ALD gene also develop AMN, but later in life. The symptoms of AMN may be quite similar to those of multiple sclerosis, although they are quite separate diseases.

We are pleased to announce that the winner of this award is Celia Kassmann of the Max Planck Institute of Experimental Medicine in Goettingen, Germany. Through the generosity of Mark Liley and Oliver’s Army, a second award was made to Dr Aurora Pujole of Institut d'Investigació Biomédica de Bellvitge of Barcelona, Spain, to study AMN. Dr. Pujole intends to study ways to develop rational therapies for AMN, concentrating on some drugs that are already on the market for other purposes.

Drs. Kassmann and Pujole will each receive $150,000 per year for two years to complete their projects.

THANK YOU FOR VISITING OUR WEB SITE

In 2009 our web site had over 176,000 visitors from 185 countries and in 101 languages. In 2009 we opened a branch in Istanbul, Turkey. Turker Aydin is the President and was instrumental in creation of this new Branch and also created the web site which is http://www.myelinturk.org/ Thank you Mr. Aydin and welcome to the Myelin Project family.

WE NEED YOUR HELP

We are still racing the clock . The single biggest barrier to progress is our scientific research is lack of funding. Won’t you please help us today with your generous and immediate support. All gifts to the Myelin project are fully tax deductible.

You may donate online at http://www.myelin.org/en/donations/add.asp

If you are interested in helping The Myelin Project by hosting a fund raising event in your community Jean Kelley, ALD mother and Myelin Project Board member will help you get started and guide you through the process. She has been fantastic fund raiser for the Myelin Project and has offered to share her expertise and work with you to develop a successful event. There is no event or donation too small. Every little bit helps. If you are interested you may email Jean Kelley at jeanakelley@gmail.com

HAPPY NEW YEAR

Stay up to date with our RSS feeds.

18-Dec-09 11:50 AM

[firstname] [lastname], The Myelin Project Newsletter 5-Nov-09

Candace Root — Thu, 05 Nov 2009 20:38:36 GMT

Hello [firstname],

Welcome to the The Myelin Project newsletter here is some very exciting new research news.

Releases

Releases for 6-Oct-09 to 5-Nov-09

Gene therapy technique slows brain disease

Author: Natasha Pinol

Release Date: Thursday 5-Nov-09 2:00 PM

A strategy that combines gene therapy with blood stem cell therapy may be a useful tool for treating a fatal brain disease, French... [More Info]
Posted by: Candace Root

Gene Therapy Advance Saves Two Boys From Rare Brain Disease

Author: Rob Waters

Release Date: Thursday 5-Nov-09 1:00 PM

Nov. 5 (Bloomberg) -- Two seven-year-old boys with a fatal brain disease who couldn’t get bone marrow transplants were saved by... [More Info]
Posted by: Candace Root

Brain Disease Treated by Gene Therapy

Author: Lizzie Buchen

Release Date: Thursday 5-Nov-09 1:00 PM

A treatment based on HIV finds first success in humans. The successful treatment of a brain disease marks a big step forward for gene... [More Info]
Posted by: Candace Root

Scientists Halt Brain Disease with New Gene Therapy

Author: Elizabeth Fullerton

Release Date: Thursday 5-Nov-09 1:00 PM

LONDON (Reuters) - Scientists have managed to halt a rare and fatal brain disease with an experimental gene therapy technique using a... [More Info]
Posted by: Candace Root

Duke Studies New Approach in Fetal Transplants for Metabolic Disorders

Author: Joanne Kurtzburg

Release Date: Thursday 15-Oct-09 2:00 PM

October 13th, 2009 --> (PhysOrg.com) -- Researchers say a new development in cord blood transplants for inherited metabolic disorders... [More Info]
Posted by: Candace Root

Stay up to date with our RSS feeds.

5-Nov-09 2:38 PM

Help Someone with a Demyelinating Disease

Kim Hodgson — Wed, 09 Sep 2009 17:00:00 GMT

Untitled Document

Another Wayne Osteen Home Raffle Benefiting The Myelin Project.

Wayne Osteen a local home builder in Amarillo, Texas and is building a new home that will be raffled off as a fund raiser to benefit The Myelin Project.The home is under construction in the new City View addition of Amarillo, Texas. The home will be raffled off in a reverse raffle on Sunday October 18, 2009. Only 4900 tickets will be sold, 100 finalists will be selected and will participate in the reverse raffle.

Win a house in City View and at the same time help someone with a demyelinating disease. Funds raised will be used to fund future research of The Myelin Project.

Raffle tickets are only $50.00!

Acutal image of the house

9-Sep-09 12:00 PM

The Myelin Project Home Giveaway Raffle

Kim Hodgson — Wed, 01 Jul 2009 14:00:00 GMT

Another Wayne Osteen Home Giveaway Benefiting The Myelin Project. Wayne Osteen a local home builder in Amarillo, Texas and is building a new home that will be raffled off as a fund raiser to benefit The Myelin Project. The home is under construction in the new City View addition of Amarillo, Texas. The home will be raffled off in a reverse raffle on Sunday October 18, 2009. Only 4900 tickets will be sold, 100 finalists will be selected and will participate in the reverse raffle for the home giveaway.

Actual image of the house

Make your dreams come true, win a house in City View and at the same time help someone with a demyelinating disease. Funds raised will be used to fund future research of The Myelin Project.

Raffle tickets are only $50.00! Purchase yours online today!

1-Jul-09 9:00 AM

[firstname] [lastname], The Myelin Project Newsletter 19-May-09

Candace Root — Tue, 19 May 2009 15:56:40 GMT

Untitled Document

Hello [firstname],

Welcome to the The Myelin Project newsletter of upcoming events, articles, jobs and more from our membership.

Calendar Events
Articles
Releases

Calendar Events for 19-May-09 to 1-Jul-09

6th Annual Got the Nerve Triathlon
Speaker's Name:
Day: Saturday 23-May-09 8:00 AM
Location: Mt. Gretna Mt. Gretna, PA 17064
Summary: 6TH ANNUAL GOT THE NERVE TRIATHLON Saturday May 23, 2009...
Add to Calendar
Posted by: Candace Root

Lorenzo Odone Memorial
Speaker's Name:
Day: Saturday 30-May-09 9:00 AM
Location:
Summary: May 30, 2009 will be the one year anniversary of Lorenzo Odone's death. Please join us and Augusto in remembering Lorenzo in a moment of silence to honor the memory of Lorenzo and his brave fight with ALD. ...
Add to Calendar
Posted by: Candace Root

Articles for 5-May-09 to 19-May-09

Treating The Other Face of X-ALD -- Adrenomyelineuropahty

Author: Margaret Weis

Release Date: Tuesday 19-May-09 10:30 AM

Treating the Other Face of X-ALD - Adrenomyeloneuropathy It is a great pleasure to announce the launch of the Augusto Odone New Investigator Award, a project co-funded by The Myelin Project and Oliver’s Army http://www.oliversarmy.org/ Young scientists embarking on their research career are invited to submit their plans for a project aimed at finding treatments for adrenomyeloneuropathy (AMN). This debilitating disorder and X-linked adrenoleukodystrophy (X-ALD) are caused by a mutation in... [More Info]
Posted by: Candace Root

Releases for 19-Apr-09 to 19-May-09

NORTHWOOD SCHOOL STUDENTS RAISE MONEY FOR MYELIN DISEASE RESEARCH

Author: Candace Root

Release Date: Thursday 14-May-09 10:00 AM

The Myelin Project Each year the student body raises money for The Myelin Project which was established in 1989 with the aim of... [More Info]
Posted by: Candace Root

MS NEWS - Ex-Salesman Uses Net to Inform, Persuade

Author: Stuart Schlossman

Release Date: Thursday 7-May-09 11:00 AM

You may read the article in its entirety here ... [More Info]
Posted by: Candace Root

Stay up to date with our RSS feeds.

19-May-09 10:56 AM

Treating The Other Face of X-ALD -- Adrenomyeloneuropathy

Margaret Weis — Tue, 19 May 2009 15:30:00 GMT

Treating the Other Face of X-ALD - Adrenomyeloneuropathy

It is a great pleasure to announce the launch of the Augusto Odone New Investigator Award, a project co-funded by The Myelin Project and Oliver’s Army http://www.oliversarmy.org/ Young scientists embarking on their research career are invited to submit their plans for a project aimed at finding treatments for adrenomyeloneuropathy (AMN). This debilitating disorder and X-linked adrenoleukodystrophy (X-ALD) are caused by a mutation in the same gene (known as the ALD gene). While X-ALD has been the focus of much research, very little is known about AMN. This new award is intended to help bridge the gap.

Most of the visitors to this website know something about X-ALD. This genetic disease affects about one-third of boys who carry the X-ALD gene, causing loss of most normal neurologic functions within one or two years. Fewer than 20 years ago, X-ALD was invariably fatal. Thanks, in part, to The Myelin Project, substantial progress has been made in treating X-ALD. The day is near when the final work on a newborn screening test will be complete. The test will enable doctors to identify all boys who carry the X-ALD gene. Treating pre-symptomatic boys with Lorenzo’s Oil significantly reduces the chances that X-ALD will develop. For those boys who develop symptoms despite Lorenzo’s Oil therapy, there remains the option of a bone marrow or cord blood transplant. While still risky, the success rates of bone marrow transplantation have improved significantly in recent years.

Many visitors to this website have not even heard of AMN. This disorder affects the other two-thirds of the males and about one-half of the females who carry the X-ALD gene. AMN is part of the complex of diseases caused by mutations in the ALD gene. In an affected family in which two boys have the same mutation, one may develop ALD and die early, while the other may remain asymptomatic until his 20’s when he develops AMN. X-ALD and AMN have quite different symptoms. AMN is characterized by loss of spinal cord and peripheral nerve function resulting in stiffness, ataxia, weakness to paralysis and sometimes cognitive defects showing that in some men with AMN, the brain is also involved.

In men, symptoms of AMN most often develop between 20 and 30 years of age, when they are just beginning to build a career and start a family. Women become symptomatic later in life, in their 40’s or 50’s, and while the symptoms are usually less severe than men with AMN, they can be serious and debilitating.

If you would like to make a contribution to the Augusto Odone New Investigator Award for AMN Research you may donate online http://www.myelin.org

19-May-09 10:30 AM

The Myelin Project Needs Your Support!

Kim Hodgson — Thu, 16 Apr 2009 16:00:00 GMT

Untitled Document

The Myelin Project needs your support in continuing our mission to end human suffering by those inflicted with demyelinating diseases.

You can show your support by donating to the causes below.

Support research for Leukodystrophies and acquired diseases such as multiple sclerosis Donate online through Facebook. Learn more.

Mission: To raise money to fund accelerated research for myelin disease.

Support Development of a Newborn Screening Test for the Adrenoleukodystrophy (ALD) gene Donate online through Facebook. Learn more.

Mission: To detect ALD gene in newborns so life saving interventions such as Lorenzo’s Oil therapy can be started before clinical symptoms occur.

The Myelin Project is now on Facebook. Become a Fan and stay up to date with the latest Myelin Project news and research updates.

16-Apr-09 11:00 AM

2008 Myelin Project Newsletter

Candace Root — Mon, 29 Dec 2008 18:00:00 GMT

/attachments/wysiwyg/1/2008Newsletter.pdf

29-Dec-08 12:00 PM

How Schwann Cells Might Be Altered So That They Might Be Better Candidates For Myelin Transplantation

Anne Baron-Evercooren, PhD — Wed, 10 Dec 2008 20:00:00 GMT

Dr. Anne Baron-Evercooren, Centre Hospitalier Universitaire, Pitié-Salpêtrière, Paris, presented her investigation of how Schwann cells might be altered so that they might be better candidates for myelin transplantation. By forcing the cells to express an enzyme, sialyltransferase, their ability to migrate was greatly improved.

Schwann cells (SC) form myelin in the peripheral nerves and are easy to get. Despite their obvious repair potential in the central nervous system (CNS), several studies indicated that SC aren’t effective in repairing CNS myelin. Other cell types (olfactory ensheathing cells, neural stem cells and oligodendrocytes) can repair CNS myelin, but are not very easy to get. Dr. Baron-Van Evercooren’s laboratory has explored some of the differences between SC and these other cell types. All of the myelin forming cells, including the SC, express NCAM, a specific protein, on their surface. However, the NCAM of the CNS myelin forming cells is “decorated” with a specific carbohydrate, while the NCAM of the SCs is “plain”.

To solve this problem, Dr. Baron-Evercooren and her associates have developed a method of getting SCs to produce “decorated” NCAM. After characterizing the modified SC cells in culture, they were transplanted to mice that had spinal cord demyelination. The modified SC were much more efficient at repairing the demyelination than the control SC. These results underline the potential therapeutic benefit of genetically modifying SC to overcome their poor migratory property and promote their repair potential in demyelinating disorders of the CNS. Dr. Baron-Evercoorn’s work has been supported by WFL and INSERM

10-Dec-08 2:00 PM

Identifying Cell Types That Might Be Useful In Re-myelination

Violetta Zujovic, PhD — Wed, 10 Dec 2008 20:00:00 GMT

Violetta Zujovic, Ph.D., Centre Hospitalier Universitaire, Pitié-Salpêtrière, Paris, reported on her work to identify cell types that might be useful in re-myelination.

During development, the entire nervous system begins as a mass of cells called the neural crest. Boundary cap cells (BC) are descended from neural crest cells. The BCs migrate to the boundary between the central (brain and spinal cord) and peripheral (sensory and motor nerves) divisions of the nervous system. BCs are important because they are the ancestors of Schwann cells (the myelin forming cells of the peripheral nerves). In addition, BCs are also the ancestors of some of the nocioceptive (pain-sensing) nerve cells of the dorsal root ganglia (part of the spinal cord).

To gain insights in BC’s behaviour in the demyelinated central nervous system, BCs were isolated from developing mouse brain. When BCs were transplanted to a demyelinated region of a mouse spinal cord, they were able to multiply, thus efficiently repairing the lesion. When grafted at a distance (one vertebra away) from the lesion, the BCs were not only able to multiply, but they and their descendents migrated toward the lesion. The migrating cells colonized and repaired the demyelinated lesion. Interestingly, the BCs were even more efficient at colonizing the demyelinated region than Schwann cells transplanted directly to the lesion.

Thus, there is evidence that boundary cap cells are able to remyelinate central nervous system axons. This evidence strongly indicates that boundary cap cells are of interest as a potential method of central nervous system myelin repair.

10-Dec-08 2:00 PM

Advances In Hematopoietic Stem Cell Based Gene Therapy For The Treatment of Metachromatic Leukodystrophy

Alesssandra Biffi, MD — Wed, 10 Dec 2008 20:00:00 GMT

Dr. Alessandra Biffi, of the San Raffaele Scientific Institute, Milan, Italy, reported on her group’s advances in hematopoietic stem cell based gene therapy for the treatment of metachromatic leukodystrophy.

Metachromatic Leukodystrophy (MLD) is a demyelinating disease due to inherited deficiency of arylsulfatase A (ARSA). In the absence of effective therapies, MLD is a disease with an urgent medical need. This is particularly important, since donor hematopoetic stem cell (HSC) transplant in MLD has met with mixed results. In a mouse model, ARSA can be transplanted to the central nervous system. Specifically, the ARSA gene was transplanted to HSC of MLD mice. Then the modified HSCs were transplanted back to the MLD mice. After this treatment, the manifestations of MLD were corrected. Bboth the feasibility and safety of this therapeutic strategy were tested in a pre-clinical model. Using HSCs from human MLD patients, a similar strategy has successfully corrected the ARSA deficiency. These data have provided the basis for the next step, giving the treated HSCs back to an MLD patient. This clinical trial of HSC gene therapy for the treatment of MLD patients is expected to start by the second quarter of 2009. As in the mouse model, the protocol is based on isolating HSCs from the MLD patients, transplanting the normal ARSA gene into the HSCs, then giving the cells back to the patient. This strategy is expected to avoid the potential complications of graft vs. host disease and to achieve sustained long term ARSA expression in MLD patients.

10-Dec-08 2:00 PM

Long-term Outcome of Bone Marrow Transplantation in a Mouse Model of Krabbe’s Disease

Yiochi Kondo, PhD — Wed, 10 Dec 2008 20:00:00 GMT

Dr. Yoichi Kondo, University of Wisconsin, discussed the long-term outcome of bone marrow transplantation in a mouse model of Krabbe’s disease

Bone marrow transplantation (BMT) or umbilical cord blood transplantation are the only therapies available to date for globoid cell Leukodystrophy (GLD, Krabbe disease). However, they do not cure the disease. To discover why, Dr. Kondo investigated twitcher (twi) mice, a model of GLD. If BMT was performed on these mice 10 days after birth, the twi mice lived for an average of 168 days. Those animals that did not receive BMT lived for only about 51 days. When compared to control twi mice, animals that received BMT had better myelin formation at 45 days of age. However, at 200 days, the mice receiving BMT had extensive loss of myelin and displayed evidence of progressive neuronal damage. This study demonstrates that enzyme replacement by simple BMT is not sufficient for the long-term treatment of GLD.

10-Dec-08 2:00 PM

Novel Strategy for Gene Therapy of Globoid Cell Leukodystrophy.

Alessandra Biffi, MD — Wed, 10 Dec 2008 20:00:00 GMT

Dr. Alessandra Biffi also reported on a novel strategy for gene therapy of globoid cell leukodystrophy.

Globoid leukodystrophy (GLD), also known as Krabbe Disease, is a genetic disease whose victims are unable to make galactocerebrosidase (GALC). The GALC enzyme helps to metabolize some of the lipid components of myelin. A gene therapy strategy for GLD based on hematopoietic stem cells (HSC) is under development. The gene transfer can be made by using a virus, called the lentivirus (LV). This has proved to be an efficient method to transfer the GALC gene to HSCs The treated cells are able to express GALC at levels that are very high. However, this high level of GALC expression may also cause functional impairment, or even death, of the HSCs. It could be that the unnaturally high levels of GALC expressed by the treated HSCs are damaging to them. However, GALC doesn’t damage the descendents of HSCs. This suggests a new therapeutic strategy that is now being tested. The LV vector has been modified, so that when the GALC gene is transplanted to the HSCs, the GALC gene lies dormant until the HCS divides and differentiates. That is, the GALC gene is not expressed until it is safe to do so. This novel strategy avoids GALC damage in HSCs, while allowing sustained GALC expression in the progeny of the HSCs. Evaluation of this strategy is in progress.

10-Dec-08 2:00 PM

Inflammatory Neurodegeneration Caused by Inactivation of Peroxisome Function in Oligodendrocytes

Celia Kassman, PhD — Wed, 10 Dec 2008 20:00:00 GMT

Dr. Celia Kassmann of the Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine discussed her recent studies on inflammatory neurodegeneration caused by inactivation of peroxisome function in oligodendrocytes.

X-linked adrenoleukodystrophy (X-ALD) is the most frequent juvenile leukodystrophy. It is caused by mutations of the adrenoleukodystrophy protein (ALDP), a peroxisomal membrane protein of unknown function. Attempts to create a mouse model for X-ALD by inactivating the ALDP gene have failed. Although ALDP deficient mice accumulate very long chain fatty acids (VLCFA) inflammatory brain demyelination does not occur. Dr. Kassmann investigated how peroxisomes in oligodendrocytes (the cells that form myelin in the brain) help maintain CNS myelin. Her laboratory generated mutant mouse that lacked functional peroxisomes only in oligodendrocytes. She found that peroxisomes in these cells are essetial for maintaining white matter (myelin) tracts. The mutant mice developed normally, but within several months exhibited ataxia, tremor, and premature death. They also showed widespread axonal degeneration, progressive subcortical demyelination, and a strong brain inflammation. The exact function of oligodendroglial peroxisomes is still unknown. But, Dr. Kassmann's studies suggest that functional peroxisomes are required for axonal support.

10-Dec-08 2:00 PM

Newborn Screening in X-linked Adrenoleukodystrophy and Other Peroxisomal Disorders

Gerald Raymond, PhD — Wed, 10 Dec 2008 20:00:00 GMT

Dr. Gerald Raymond, of The Kennedy Krieger Institute, Johns Hopkins University, presented a summary of current progress in the development of newborn screening in adrenoleukodystrophy

Adrenoleukodystrophy (ALD) is an X-linked disorder that has variable manifestations. In young boys, these may include adrenal insufficiency and loss of myelin in the brain. In adults, both men and women, there may be a progressive spastic paraparesis. Boys who inherit the ALD gene require careful monitoring for adrenal and cerebral disease. There are life-saving interventions for this disorder. Experimental therapy with diet and Lorenzo’s oil may reduce the incidence of childhood cerebral disease. If these fail, early, appropriate use of hematopoietic stem cell therapy appears to arrest disease progression. However, these therapies are successful only if begun before clinical symptoms develop.

Virtually all persons with the ALD gene have high levels of very long chain fatty acids (VLCFA) in their plasma. Using this biochemical abnormality, a method has been developed that can detect elevated VLCFA in very small volumes of blood. This method is adaptable to regional newborn screening offering early diagnosis and intervention in adrenoleukodystrophy and other peroxisomal disorders. The sensitivity of the assay was tested in over 500 newborn blood samples, some of which were from children known to have the ALD gene. The assay was able to identify all of the affected samples. Work is now underway to test 5000 samples to confirm the sensitivity and specificity. Successful completion of this phase will establish the assay as a good way to screen all newborn children for the ALD gene. Appropriate monitoring can be initiated immediately. It is anticipated that this would greatly improve the clinical outcome for these children.

10-Dec-08 2:00 PM

Treatment for Pelizaeus-Merzbacher Disease

Drs. Klaus Armin Nave & Celia Kassman — Wed, 10 Dec 2008 20:00:00 GMT

Although Dr. Klaus-Armin Nave, Department of Neurogentics, Max-Planck-Institute of Experimental Medicine, was unable to attend the meeting in Ft. Worth, his pre-clinical work on a treatment for Pelizaeus-Merzbacher disease was presented by his colleague, Dr. Celia Kassmann.

Investigators in Dr. Nave’s lab are using a mutant mouse model to test a new drug therapy for Pelizaeus-Merzbacher disease (PMD). This severe leukodystrophy characterized by ataxia, mental retardation, epilepsy and premature death. No therapy is currently available. Like most humans with PMD, Dr. Nave’s mutant mice over-express the Plp1 gene. So, the mice were used to test the effect of a new drug (ZK230211) on Plp1 gene expression. Motor function ws measured during the 10 week trial. At the end of the trial, Plp1 gene expression was measured in the brains of the mice. The treated animals expressed 15% less Plp1 than the control mutant mice. Importantly, ZK230211-treated mutants had significantly better motor control. Most relevant, there were about 30% more myelinated axons in the corticospinal tract of treated mutants, as compared to the controls. This "proof of principle" trial suggests that it is possible to develop a ‘rational drug therapy’ for PMD patients having Plp1 gene duplications.

10-Dec-08 2:00 PM

Introducing Stem Cell Based Myelin Repair Therapies in Patients with Multiple Sclerosis

Neil Scolding, FRCP, PhD — Wed, 10 Dec 2008 19:15:00 GMT

Professor Neil J. Scolding, FRCP PhD, University of Bristol Institute of Clinical Neurosciences, U.K., provided a report of his studies of bone-marrow derived cells for the treatment of multiple sclerosis.

About 30 years ago, investigators began to think that cell therapies might be useful to treat loss of myelin caused by multiple sclerosis (MS). The disease has proved more complex, and tissue repair in the brain and spinal cord more challenging than we first thought. Many factors contribute to myelin and nervous tissue damage in MS. Cells capable of myelin repair are present in damaged areas but nonetheless do not seem to repair myelin. This might mean that simply adding more myelin-making cells to lesions won’t be enough to help in this disease. Professor Scolding is studying bone marrow derived stem cells. These have a very limited capacity for turning into myelin forming cells. But they seem to stimulate repair processes that are key to tissue regeneration in MS. A small safety study of these cells in six patients with chronic MS is nearing completion. The final report will be made when the data analysis is finished. Dr. Scolding has said, “We are grateful indeed to the Myelin Project for our funding, without which this trial would have proved very difficult to complete.”

10-Dec-08 1:15 PM

Therapeutic Plasticity of Neural Stem Cells

Gianvito Martino, MD — Wed, 10 Dec 2008 19:00:00 GMT

Dr. Gianvito Martino of the Institute of Experimental Neurology at the San Raffaele Institute in Milan, Italy reported on the therapeutic plasticity of neural stem cells.

Recent evidence challenges the conventional view that neural stem/precursor cells (NPCs) protect and repair the central nervous system (CNS) simply by replacing damaged cells. Rather, NPCs may also promote CNS repair by a “bystander” effect. In other words, NPCs may release a mixture of neuroprotective molecules at the site of tissue damage. These protective substances are released in a coordinated manner, in response to the specific needs of the damaged tissue. Even in undamaged tissue, NPCs produce these molecules, which and help to maintain nerve tissue throughout life. These protective agents may be common to many kinds of somatic stem cells (e.g. mesenchymal stem cells). These kinds of stem cells don’t normally differentiate into neural cells, yet they may efficiently promote CNS repair. Thus, the repair capacity of stem cells may well include their ability to adapt their fate and function(s) to specific needs in response to different pathological conditions (therapeutic plasticity). The discovery that transplanted NPCs may protect the brain through bystander strategies is of pivotal importance for the future of stem cell based therapeutics.

10-Dec-08 1:00 PM

How Studies in the Laboratory Demonstrate an Unexpected Connection to Other Aspects in Scientific Reseach

Robin Franklin, PhD — Wed, 10 Dec 2008 19:00:00 GMT

Dr. Robin Franklin, Professor of Neuroscience, Cambridge Center for Brain Repair, University of Cambridge, U.K., related how studies in his laboratory demonstrate an unexpected connection to other aspects science.

Over the last year Dr. Franklin’s lab has been continuing its work on how the brains own stem cells are able to replace lost myelin-forming cells (oligodendrocytes). Doing so is expected to help identify therapeutic targets that will help to enhance remyelination in patients. In collaboration with other laboratories several new pathways have been identified that either encourage or prevent stem cells becoming new oligodendrocytes. At this year’s meeting Professor Franklin explained how some of these pathways are also involved in the formation of cancers. Of course, cancer scientists have for some time been developing drugs to influence these pathways. Thus, some of the developments that are being made in cancer treatment may, unexpectedly, have additional roles in encouraging myelin regeneration in myelin diseases. There is still some distance to go in realising the potential of such approaches but current signs indicate that this is a promising line of investigation.

10-Dec-08 1:00 PM

Research from Dr. Ian Duncan, University of Wisconsin

Ian Duncan, Ph.D. — Wed, 10 Dec 2008 18:00:00 GMT

Dr. Ian Duncan’s group from the University of Wisconsin summarized three new (and as yet unpublished) projects. Two of them involved research on a mutant mouse (op) that is not able to develop certain cell types that are important in bone remodeling and in the immune system.

The first project studied the numbers of microglial cells, which are part of the immune system in the central nervous system. The microglia are important in diseases of brain inflammation, such as multiple sclerosis. Dr. Duncan’s lab found that there are fewer microglial cells in the white matter of op mice as compared to control mice. However, the numbers of microglia in the grey matter were not different between the two groups. While microglia in both mutant and control mice responded to a wound in the cerebral cortex (part of the brain grey matter), the change in the op mice was less than the control. These findings make the op mouse a useful model in which to explore the role of microglia in inflammatory diseases.

The second project on the op mouse studied the optic nerve. Because op mice have abnormal bone remodeling, the surrounding bone compresses their optic nerve. At the compression site, there are few oligodendrocytes, the cells that make brain myelin. So, there is little or no myelination at this site. Nerve conduction through the area of non-myelination is severely affected. The group plans to study whether the oligodendrocytes die because compression reduces their blood supply.

Finally, Dr. Duncan reported on a new model of chronic demyelination and remyelination in the cat, induced by feeding the animals an experimental diet. Only the myelin sheath appears to be affected, with axons remaining intact. When the cats are returned to a normal diet, they recover neurologically with evidence of remyelination throughout the entire CNS. This model proves unequivocally, and for the first time, that remyelination restores function in a large animal model and confirms that remyelination is a major therapeutic target in demyelinating disease.

10-Dec-08 12:00 PM