Could new study lead to a treatment for CMT?

A new study into a subtype of Charcot Marie Tooth, which was conducted by researchers from The Scripps Research Institute (TSRI) and the Salk Institute for Biological Studies, could one day lead to a treatment for patients with Charcot Marie Tooth.

The researchers found that a mututation in protein called glycyl-tRNA synthetase (GlyRS) could led to nerve damage in CMT2D, and they say  one day it might be possible to target this malfunctioning protein and restore normal function in patients with CMT.

In a press release, TSRI Professor Xiang-Lei Yang, senior author of the new study with Samuel Pfaff, a neuroscience professor at the Salk Institute and a Howard Hughes Medical Institute investigator, said:

“This is the first major advancement toward a molecular mechanistic understanding of CMT subtype CMT2D.”

“These findings will help us develop future diagnostics and treatments.”

Researchers found that GlyRS can attach to  a growth factor known as vascular endothelial growth factor (VEGF)and interfere with the connection between the brain and the limbs. However, a study on mice found that by increasing levels of VEGF, it was then possible for it to out compete GlyRS, and the mice with CMT were able to gain more muscle strength and had fewer symptoms of CMT.

Commenting on this discovery Plaff said:

“This solves a long-running mystery of how a gene mutation damages the neurons that carry information from the spinal cord to our muscles, resulting in a range of sensory and movement problems.”

It’s an exciting finding, as we were able in experiments to reduce the symptoms of the disease by targeting the activity of these proteins.

The next stage is to “develop targeted strategies that could recognize and intercept GlyRS mutants before they block VEGF; this could have implications for other forms of CMT.

The study was published in the journal Nature on October 21st, 2015.

Story link: http://www.newswise.com/articles/view/641749/?sc=dwhn

Alert cards for patients suffering from muscle wasting conditions

Muscular Dystrophy UK has made an alert card available for people who have Duchenne Muscular Dystrophy, Charcot Marie Tooth, limb girdle muscular dystrophy and Spinal Muscular Dystrophy.

Muscular Dystrophy UK say they have already sent out more than 4,000 of the cards and they have received plenty of positive feedback from the recipients.

Soon, Muscular Dystrophy UK plans to make the cards available for people withother muscle wasting conditions such as Becker muscular dystrophy and myotonic muscular dystrophy types 1 and 2.

There are also plans to make a care plan available online that will be helpful for anyone living with a muscle wasting condition.

Further information can be found at: http://www.musculardystrophyuk.org/news/muscular-dystrophy-uk-continues-to-hear-great-feedback-on-new-alert-cards/

Researchers at Rush University Trial Stem cell therapy

Researchers at Rush University are studying the potential of using stem cells to help treat recently acquired spinal cord injuries.

The therapy would use progenitor cells; these have the potential to improve nerve function.

Dr. Richard G. Fessler, professor of neurological surgery at Rush University Medical Center and principal investigator for the Phase 1 clinical trial involving AST-OPC1 (oligodendrocyte progenitor cells, said:

“There are currently no therapies which successfully reverse the damage seen in the more than 12,000 individuals who suffer a spinal cord injury each year in the United States alone.”

“These injuries can be devastating, causing both emotional and physical distress, but there is now hope. This is a new era where we are now able to test whether a dose of stem cells delivered directly to the injured site can have an impact on motor or sensory function.”

“If we could generate even modest improvements in motor or sensory function, it would result in significant improvements in quality of life.”

A clinical trial is currently underway to check the safety of this form of therapy. During the trial, AST-OPC1 will be given in three increasing doses to patients who have suffered a complete spinal injury.

AST-OPC1 will need to be injected within 14-30 days following the spinal injury and the patients will need to be aged 18-65. Neurological examinations and imaging will track the safety and action of AST-OPC1.

Dr. Fessler said:

“In the future, this treatment may be used for peripheral nerve injury or other conditions which affect the spinal cord, such as MS or ALS.”

Source: https://www.rush.edu/news/press-releases/regenerating-nerve-tissue-spinal-cord-injuries

Study shows stem cell transplants could stop progression of MS

New research indicates that stem cell therapy has the potential to stop the progress of Multiple Sclerosis. The study, which was funded by the National Institutes of Health, involved giving patients immunosuppressive therapy and then transplanting blood forming stem cells into the patient.

The trial was conducted over a three-year period and involved patients with the relapsing-remitting form of MS. It was found that the majority of patients that received the high dose immunosuppressive therapy coupled with an autologous hematopoietic cell transplant had no new brain lesions and their disability did not worsen. Moreover, it was found that this form of therapy had few side effects, although some participants in the trial did experience infections and gastrointestinal problems.

Commenting in a press release, NIAID Director Anthony S. Fauci, M.D., said:

“These promising results support the need for future studies to further evaluate the benefits and risks of HDIT/HCT and directly compare this treatment strategy to current MS therapies.”

“If the findings from this study are confirmed, HDIT/HCT may become a potential therapeutic option for people with this often-debilitating disease, particularly those who have not been helped by standard treatments.”

The therapy was tested on 25 volunteers; all of them have the relapsing-remitting form of multiple sclerosis. The participants had all been on medication for their condition, but their neurological disability had continued to worsen.

During the trial, blood forming stem cells were taken from the patients and they were given high-dose chemotherapy.

“Notably, participants did not receive any MS drugs after transplant, yet most remained in remission after three years,” said Daniel Rotrosen, M.D., director of NIAID’s Division of Allergy, Immunology and Transplantation. “In contrast, other studies have shown that the best alternative MS treatments induce much shorter remissions and require long-term use of immunosuppressive drugs that can cause serious side effects.”

Participants will be followed for a five-year period; information of any side effects will be recorded and larger studies to determine the therapies effectiveness are planned in the future.

Details of the study have been published in the December 29, 2014 issue of JAMA Neurology.

Reference:

RA Nash et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a three-year interim report. JAMA Neurology DOI: 10.1001/jamaneurol.2014.3780 (2014).

The original press release can be viewed here.

My wishes for you

Thank you for this. I have reblogged it.

CMT and Me

To all those with Charcot-Marie-Tooth disease I wish you:

Patience to put up with what this crazy disease throws at us

Perseverance to keep going when the going gets really tough

Curiosity to keep looking for new ways to manage the losses you experience

A sense of humour so you don’t take yourself too seriously. Everyone has to cope with something.

The awareness to live in the present. Trying to project what CMT will do to you in the future is futile.

The ability to be happy that you are alive. Life can be good if you let it and the world can be beautiful, in spite of the daily news, if you stop worrying long enough to really look.

May 2015 be a year of self-discovery and love because in my books those are the two things that really matter.

Linda and Ron

Love

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Breakthrough allows paralysed man to walk again

A pioneering treatment that was developed by researchers at the University College London has led to a paralysed man being able to walk again. The surgery, which involved the transplantation of stem cells, was carried out by surgeons at the Wroclaw Hospital in Poland.

The development has been made possible due to the work of Professor Raisman. Professor Raisman discovered OECs in the eighties, and in 1997 trials carried out in rats showed that they could be used to help manage spinal injuries. Professor Raisman has spent a decade developing techniques to enable OECs to be used for spinal repair in humans; the recent breakthrough is a result of the research.

Professor Geoff Raisman, Chair of Neural Regeneration at the UCL Institute of Neurology, said:

“It is immensely gratifying to see that years of research have now led to the development of a safe technique for transplanting cells into the spinal cord. I believe we stand on the threshold of a historic advance and that the continuation of our work will be of major benefit to mankind. I believe we have now opened the door to a treatment of spinal cord injury that will get patients out of wheel chairs. Our goal now is to develop this first procedure to a point where it can be rolled out as a worldwide general approach.”

Darek Fidyka, a Polish national, was left paralysed in 2010 after he was stabbed a number of times in the back. He had undergone various different forms of rehabilitation in the past, however, none of these were successful.

The surgery to restore function in Fidyka’s limbs involved taking olfactory ensheathing cells (OECs) from the nose and then transplanting them into the spinal cord. Within months of the treatment, Fidyka began to experience muscle growth in his thigh muscle, and in less than six months he was able to walk with the assistance of a physiotherapist and leg brace. Two years after the surgery, Fidyka can now walk with a frame.

Commenting on his gradual recovery, Darak Fidyka said:

“I think it’s realistic that one day I will become independent. What I have learned is that you must never give up but keep fighting, because some door will open in life.”

The research was funded by UK Stem Cell Foundation and the Nicholls Spinal Injury Foundation; details of the research have been published in the journal Cell Transplantation.

The research paper can be found here.

 

Source: https://www.ucl.ac.uk/news/news-articles/1014/211014-UCL-research-helps-paralysed-man-recover-function

Hope on the Horizon?

Researchers from the Department of Neurogenetics at the Max Planck Institute of Experimental Medicine and University Medical Centre Göttingen believe that they might have found a potential therapy for Charcot Marie Tooth Type 1A, the most common of the hereditary neuropathies.

Electron microscopic images of cross sections of nerves in a healthy rat (left), a rat suffering from CMT1A (centre) and a rat suffering from CMT1A that has been treated with neuregulin-1 (right). The neuregulin-1 treatment leads to improved myelination in the CMT1A rat model, which comes close to that of healthy animals.

Credit: © Fledrich et al, Nat. Med. 2014

The researchers discovered that the maturity of Schwann cells is impaired in rats with the disease. These cells would usually provide insulation for the myelin sheaf, which enables the smooth functioning of nerve impulses. However, when the Schwann cells don’t mature correctly, then this can leave the nerves without a sufficient amount of myelin.

According to the researchers, a nerve growth factor called  neuregulin-1 has shown “immense therapeutic potential”. Rats treated with neuregulin-1 have more myelinated nerve fibres and fewer symptoms of CMT.

Commenting on the research, co-author Ruth Stassar,said: “In genetically modified rats, even a brief neuregulin-1 treatment within the first two weeks of life improves the animals’ disease symptoms until they reach adulthood.”

Scientists and researchers from Michael Sereda’s Research Group plan to conduct further studies to “drive forward the development of a treatment for Charcot-Marie-Tooth disease type 1A”. However, it will be a long time before the growth factor can be used on patients as neuregulin-1 is not safe for use in patients; the researchers intend to use drugs that can imitate the neuregulin-1 signalling pathways when they undertake further studies.

Muscle weakness seen in alcoholism linked to mitochondrial repair issues

This isn’t about CMT, but  I received this press release from the National Institutes of Health and I thought it was worth sharing:

Muscle weakness from long-term alcoholism may stem from an inability of mitochondria, the powerhouses of cells, to self-repair, according to a study funded by the National Institutes of Health.

In research conducted with rats, scientists found evidence that chronic heavy alcohol use affects a gene involved in mitochondrial repair and muscle regeneration.

“The finding gives insight into why chronic heavy drinking often saps muscle strength and it could also lead to new targets for medication development,” said Dr. George Koob, director of the National Institute on Alcohol Abuse and Alcoholism, the NIH institute that funded the study.

The study is available online in the April issue of the Journal of Cell Biology. It was led by Dr. Gyorgy Hajnoczky, M.D., Ph.D., director of Thomas Jefferson University’s MitoCare Center, Philadelphia, and professor in the Department of Pathology, Anatomy and Cell Biology.

Mitochondria are cellular structures that generate most of the energy needed by cells. Skeletal muscle constantly relies on mitochondria for power. When mitochondria become damaged, they can repair themselves through a process called mitochondrial fusion — joining with other mitochondria and exchanging material such as DNA.

Although well known in many other tissues, the current study is the first to show that mitochondria in skeletal muscle are capable of undergoing fusion as a repair mechanism. It had been thought that this type of mitochondrial self-repair was unlikely in the packed fibers of the skeletal muscle cells, as mitochondria have little opportunity to interact in the narrow space between the thread-like structures called myofilaments that make up muscle.

By tagging mitochondria in the skeletal tissue of rats with different colors, the researchers were able to observe the process in action and confirm that mitochondrial fusion occurs in muscle cells. They also identified a key protein in the process, mitofusin 1 (Mfn1) fusion proteins, and showed that chronic alcohol use interferes with the process.

In rats that were given an alcohol diet, Mfn1 levels decreased as much as 50 percent while other fusion proteins were unchanged. This decrease in Mfn1 was coupled with a dramatic decrease in mitochondrial fusion. When Mfn1 returned to normal, mitochondrial fusion did as well.

“That alcohol can have a specific effect on this one gene involved in mitochondrial fusion suggests that other environmental factors may also alter specifically mitochondrial fusion and repair,” said Dr. Hajnoczky. He also suggested that identifying the proteins involved in mitochondrial fusion may aid in drug development for alcohol-related muscle weakness.

The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems. NIAAA also disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at http://www.niaaa.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visi twww.nih.gov.

The original press release can be read by going to:

http://www.nih.gov/news/health/apr2014/niaaa-21.htm

Healthlink launch video campaign for MS

Healthlink has launched a new video campaign called “You’ve Got This”. As part of the campaign, people living with MS are encouraged to record a short video about living with MS as a means of giving hope and encouragement to patients newly diagnosed with multiple sclerosis.

For every video that is submitted, Heathline will donate $10 to the National MS Society.

Healthlink are keen to get the news out about the campaign, as the more exposure it gets, the more money can be raised for the National MS Society.

If you have a story to share, or would like to find out more about the campaign, visit:

http://www.healthline.com/health/multiple–sclerosis/youve-got-this

Statins slow progression of advanced multiple sclerosis

Statins, the drug often prescribed to help lower cholesterol and  fight heart disease, could be used to to help fight multiple sclerosis, according to a new study that has been published in The Lancet.

No medical treatments have so far proved effective when it comes to abating secondary progressive MS. However, according to the results of the study, which included 140 patients with secondary progressive MS, the drug simvastatin has been shown to reduce brain shrinkage, which scientists believe contributes to patients’ disabilities.

The new study was led by the researchers from the Imperial College London; in a press release issued this morning, Dr Richard Nicholas, co-author of the study from the Department of Medicine at Imperial, said:

“At the moment, we don’t have anything that can stop patients from becoming more disabled once MS reaches the progressive phase.”

“Discovering that statins can help slow that deterioration is quite a surprise. This is a promising finding, particularly as statins are already cheap and widely used.”

“We need to do a bigger study with more patients, possibly starting in the earlier phase of the disease, to fully establish how effective it is.”

It is still unclear as to why statins might be beneficial to patients with MS, however, the drug has also been shown to be helpful for people with relapsing remitting  MS during small scale studies.

The study was funded by J.P Moulton Foundation, Berkeley Foundation, Multiple Sclerosis Trials Collaboration, Rosetrees Trust and the National Institute for Health Research (NIHR).