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Myostatin is a protein in muscle cells that controls muscle growth. Reducing myostatin causes the growth of pre-existing muscle cells, enlarging the muscle fibers. When myostatin is reduced in healthy animals, muscles grow significantly larger. One example of this effect is Belgian Blue cattle, which genetically lack myostatin and have visibly more muscle and less fat than average cattle.  Drugs that reduce myostatin could potentially increase muscle mass in patients with muscular dystrophies to help them compensate for lost muscle mass that results in progressive weakness. In fact, researchers have previously discovered that reducing myostatin improves muscle mass and function in a mouse model of Duchenne muscular dystrophy, which is caused by missing the protein dystrophin. Dystrophin is thought to maintain the connection between the muscle cell membrane and the surrounding tissue.

 

In their article Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy, the researchers investigated whether reducing myostatin on mice lacking dysferlin was beneficial as it was in mice lacking dystrophin. Dysferlin-deficient mice are a model for LGMD2B or Miyoshi Myopathy—collectively called dysferlinopathy. In this article, researchers used two different methods to remove or reduce myostatin from mice that lack dysferlin. First, they added the protein follistatin, which blocks myostatin function. The results initially showed the desired increase in mass, but also identified some long-term concerns. Instead of maintaining the extra muscle gained early in the experiment, animals began to rapidly lose muscle and the researchers noticed abnormalities within the muscle cells, reduced force of contraction, and greater damage to the muscle cells (measured by elevated CK levels). The drug activin receptor II, which reduces the effect of myostatin, had a less dramatic impact on muscle growth initially and also a less pronounced drop in muscle mass later, but there were still issues such as increased muscle damage. Immune system activation was observed following both activin and follistatin treatment, further indicating damage. A possible explanation is that reducing myostatin increases the size of the fibers, increasing stress on the individual muscle fibers, which are already susceptible to damage.

 

The results show that reducing myostatin has potent muscle building effects in muscular dystrophies, but may also have long-term treatment concerns for dysferlinopathy. The potential benefits of reducing myostatin need to be weight against the dangers to determine if reducing myostatin in various ways might be a possible therapy to help LGMD2B/MM patients. It also isn’t clear whether dysferlin deficiency is unique in its apparent lack of tolerance for myostatin inhibition, or dystrophin deficiency is unique in benefitting from the therapy.

Researchers analyzed newspaper articles on stem cells from 2010-2013 and found almost 70% of the articles reported that treatments would be available in 5-10 years or earlier, but these timelines are unsupported by scientific research. These inaccurate timelines give false hope and can lead patients to seek out unproven stem cell therapies.

 

Most of the news articles in the US, Canada and the UK focus on diabetes, neurological and cardiovascular diseases even though these applications are still very far from being ready for the clinic. Today, the only approved and effective stem cell treatments are bone marrow stem cell transplantation for cancers like leukemia and genetic blood diseases like thalassemia. Most of the recent clinical trials involving stem cells have focused on treating cancers or issues that arise when the immune system rejects transplants.

 

The analysis of recent news articles has also shown that the media has recently shifted the stem cell debate away from ethical concerns like whether we should allow researchers to use cells from human embryos. Now, the marketing of unproven treatments and other policy concerns are dominating headlines.

 

The take-home message from this analysis is that stem cell research is not as far along as the media may lead you to believe. Patients should try to be skeptical of media hype and discuss any potential treatments with their physicians before receiving them.

 

Read the full text article here:

http://stm.sciencemag.org/content/7/278/278ps4.full

Telomerase Activation (TA) Sciences has been accused by former employee Brian Egan of conducting deceptive business practices, in promoting a herbal extract as having anti-ageing properties.

 

The lawsuit is focused on a pill called TA-65 which the company claims can slow or reverse degenerative effects caused by aging telomeres. Telomeres are nucleotide sequences that protect the ends of chromosomes when DNA replicates. Telomeres continue getting shorter and once they are gone, cells cannot reproduce because their DNA can no longer replicate. However, a telomerase enzyme exists that lengthens telomeres, and can slow or reverse degenerative diseases.

 

Egan, who took TA-65 was later diagnosed with prostate cancer and has accused TA Sciences of being responsible for his illness. However, TA Sciences argues that he must have had this cancer before starting the pill.

 

The creation of a legitimate telomere-lengthening compound would be an important development in treating people suffering from bone marrow failure or pulmonary fibrosis. However, the false promotion of such compound would be even more harmful to these patients.

 

Read the full article here: http://www.nature.com/news/lawsuit-challenges-anti-ageing-claims-1.11090

The US District Court has ruled in favor of the FDA who claimed that the use of a patient’s own stem cells to regulate therapy should be subject to the same regulations as drug therapies.

 

A company called Regenerative Sciences takes stem cells from bone marrow, processes them, and injects them back into the patient in order to treat joint pain. However, the FDA called this procedure “unapproved biological drug product manufacturing” in 2010 and ordered the prevention of the treatment.

 

The FDA also found that the company was sacrificing patient safety due to flaws in cell processing, and the procedure includes potential transmission of communicable diseases. Regenerative Sciences’ response was that cells were not significantly changed before reinjection so it was simply routine medical practice, and proceeded to continue the procedure in a Cayman Island clinic. The concern now is that more non-FDA approved procedures will take place outside the US, such as Mexico, as a method to avoid FDA regulation.

 

Stem cell therapy has the potential to be an incredibly powerful tool in treating a wide range of diseases and therefore is a topic about which there is a lot of interest and excitement about its potential applications.  The regulation of stem cell therapies is necessary to protect patients from being exploited by unethical practices.

 

Read the full article here: http://www.nature.com/news/fda-s-claims-over-stem-cells-upheld-1.11082

Dr. Michael Sinnreich recently conducted a clinical study of a drug called bortezomib in individuals who have a particular type of mutation (called ‘missense mutations’) in the dysferlin gene. Read the full summary of the article here.

The effects of exercise on LGMD2B/Miyoshi myopathy have not yet been studied in detail, so there is no consensus on whether exercise will help or hurt patients with the disease.

 

Although there are no official recommendations, a number of patients have shared their stories with us to let us know how physical therapy has affected them. During the Jain Foundation conference in 2013, Bliss Welch talked about her experiences with physical therapy. Watch the video here: https://www.youtube.com/watch?v=AFUZKumuGOw

Stem cell therapy has been mentioned as a therapeutic option for a diverse group of diseases such as cancer, Parkinson, and muscular dystrophy.  Stem cell therapy involves introducing stem cells into patients to replace damaged tissues.  There are two main kinds of stem cells: embryonic and adult.  Embryonic stem cells are only found in developing embryos and these cells can develop into any cell type in the human body.   Adult stem cells can come from a variety of sources in the body, but are more limited in the cell types they can become.  The most well-known stem cell therapy is a bone marrow transplant which is used to treat certain cancers of the blood.  Bone marrow stem cells are adult stem cells that give rise to red blood cells that carry oxygen throughout the body and white blood cells that fight infection.

 

 In patients with a genetic disease like muscular dystrophy, stem cell therapy is a very attractive option because injection with a specific type of “stem cell” that can make muscle and express the missing protein has the potential to repair abnormal muscle function.  However, there are numerous obstacles that must be overcome to make this type of therapy possible for muscular dystrophies.  These obstacles include the identification of a stem cell type that has the ability to fuse with and become muscle and how to obtain enough cells for treatment.   While researchers have found a possible stem cell, called a mesoangioblast, that has the ability to become muscle, obtaining enough of the cells for treatment is still proving difficult. 

 

 Just as with organ transplants, the donor “stem cells” must be a “match” for the patient, or the cells will be rejected.  There are two ways to obtain a “matched” cell:  use cells directly from the patient or find someone who “matches” the patient as closely as possible.  Since it can be difficult to find a “matched” donor who is willing to provide a sample, using the patients’ own cells is a very attractive option.  However, in the case of muscular dystrophies, the patients’ cells are missing the necessary protein needed to treat the disease, so genetic correction of the patients’ own cells is necessary to make them express the missing protein. This can be accomplished by collecting the specific “stem cells” from a patient, genetically altering the cells in a test tube so that they express the missing protein, and then putting the genetically corrected cells back into the patient.  Using this method you are essentially combining stem cell and gene therapy.

 

 Recently scientists used this technique to test stem cell therapy for a type of muscular dystrophy called , Limb-girdle muscular dystrophy type 2D (LGMD2D - caused by the absence of a protein called alpha-sarcoglycan) (http://www.ncbi.nlm.nih.gov/pubmed/22745439).  In this study scientists isolated mesoangioblast stem cells from adult patients with LGMD2D.  These mesoangioblasts were then genetically corrected in a test tube and put into mice with LGMD2D to see if these genetically corrected “stem cells” could cure the mice of the disease.  The researchers showed that the LGMD2D mice were able to express the missing protein, alpha-sarcoglycan, and could run longer on a treadmill than mice that were not treated. 

 

 This research shows that there is potential for this type of therapy for muscular dystrophies, including dysferlinopathy (LGMD2B/Miyoshi).  It is difficult to estimate how long it will take before this type of therapy will be available.  The next steps in getting this technology into the clinic will be extensive studies in mice, as well as clinical trials to demonstrate the safety and effectiveness of this technique to regulatory agencies such as the US FDA.  The Jain Foundation is exploring ways to help move this research forward.  An important point to note regarding the application of this combined stem cell/gene therapy approach is that each individual needs to be genetically diagnosed by the identification of mutations in the dysferlin gene in order to be eligible for such a treatment.  If you are unsure whether or not you have been genetically diagnosed the Jain Foundation can help.  Please contact the Jain Foundation’s Director of Patient Relations, Sarah Shira, at  or 425-882-1440 or click here for more information.


Genes are the instructions manuals that tell the cell how to make the proteins that are needed for the cell to function properly.   When there is an error in those instructions (i.e. a mutation in the gene), the cell is unable to make its corresponding product (i.e. the protein) and this results in a disease.    If the part of the gene containing the error can be skipped, a slightly smaller but potentially functional protein could be made.   The parts of the gene that make the protein are called “exons” and each protein is encoded by multiple exons.  “Exon skipping” refers to the therapeutic technique by which one or more of the protein coding exons is “skipped” in order remove the mutation that is causing the disease and allow for the protein to be made.   For a simplified explanation of exon skipping, click here. Exon skipping has been assessed in several clinical trials as a possible treatment for Duchenne muscular dystrophy (DMD).  In the DMD studies, exon skipping has been shown to be relatively safe and has demonstrated some effectiveness in treating the disease (click here for more information). 

 

The question is whether “exon skipping” is a possible therapy for all forms of muscular dystrophy.  DMD is a very good candidate for the exon skipping approach because there is preexisting knowledge that dystrophin can function when truncated and there is a commonly mutated region of the gene.  DMD is caused by mutations in the dystrophin gene that result in the complete absence of the dystrophin protein.  There is a milder form of the disease called Becker muscular dystrophy (BMD) which is also caused by mutations in dystrophin, but the BMD mutations “skip” one or more exons and make a smaller form of the protein that is at least partially functional.   Researchers reasoned that if a truncated form of dystrophin could be made in DMD patients by skipping mutated exons, a less severe form of muscular dystrophy, like Becker, could result.  In addition, it is estimated that about 13% of boys with DMD have mutations in a single location of the dystrophin gene (exon 51); therefore a considerable number of DMD patients can be treated with the development of just one exon skipping strategy. 

 

It is more difficult to predict whether exon skipping is a logical therapy for dysferlinopathy (LGMD2B/Miyoshi), which is caused by mutations in the dysferlin gene that cause the absence of dysferlin protein. Unlike dystrophin, it is not known whether particular regions of the dysferlin gene are essential to make a functional protein or if any truncated dysferlin proteins will be functional. This information will be necessary prior to designing exon skipping strategies.   Also unlike DMD in which mutational “hot spots” suggest logical exons for skipping, patients with dysferlinopathy (LGMD2B/Miyoshi) have mutations across the entire dysferlin protein, with no significant concentration of mutations in any particular exons.  Therefore, multiple exon skipping strategies would have to be designed and tested for a significant number of patients to be helped, which is likely to cause regulatory hurdles and delay the availability of treatment. 

 

Given these issues, there is a considerable amount of research that still needs to be done to assess whether exon skipping will be a viable therapeutic option for dysferlinopathy and the Jain Foundation is exploring ways to help with this analysis.   An important point to note regarding the application of exon skipping as a therapeutic option is that each individual needs to know their exact mutations in the dysferlin gene to determine whether “exon skipping” would be benefical.  If you are unsure whether or not you have been genetically diagnosed the Jain Foundation can help.  Please contact the Jain Foundation’s Director of Patient Relations, Sarah Shira, at  or 425-882-1440 or click here for more information.          

Gene therapy is a therapeutic technique for genetic diseases, such as muscular dystrophies, that involves the injection of a patient with a gene carrier called a “vector.” The vector delivers to the patients’ cells a normal copy of the mutated gene to replace the protein whose absence causes the disease.    Gene therapy is a very attractive therapeutic possibility for the treatment of dysferlinopathy (i.e. a muscular dystrophy caused by mutations in the dysferlin gene).  In a recent paper, researchers reported their findings from testing gene therapy in a mouse model of dysferlinopathy (http://www.ncbi.nlm.nih.gov/pubmed?term=grose%20mendell).  In this paper, the researchers describe the addition of a normal copy of the dysferlin gene to the muscle cells of a dysferlin deficient mouse using an adeno-associated virus (AAV) gene vector.  AAV is the preferred gene vector for performing gene therapy, as it has been extensively studied, and does not cause an adverse reaction from the immune system.  Most of the gene therapy trials conducted to date have used AAV vectors.  A challenge specific to transferring dysferlin into muscles is that unlike other genes, the dysferlin gene is too big to fit inside AAV vectors or other possible gene therapy vectors. To overcome that challenge, the researchers divided the dysferlin gene into pieces and loaded the smaller pieces into individual AAV vectors.  When the AAV vectors enter the muscle cells, they release the parts of the dysferlin gene that they carry and the entire dysferlin gene is reassembled from the pieces.  One possible issue with this kind of approach is whether there will be sufficient reassembly of the pieces to make enough functional protein to improve the symptoms of the disease.  In this paper, the researchers showed that mice with dysferlin deficiency were able to express a significant amount of the full length dysferlin protein following AAV treatment and that as a result symptoms of the disease were reduced.

 

 Before this technique can be tried in human clinical trials, the researchers will need to address safety concerns that apply to gene therapy in general, like making sure the gene gets into the right cells and does not cause toxicity in the recipient. In addition, a safety assessment of delivering pieces of genes that are then reassembled will also be necessary because this approach has not been used in humans before. Thus, regulatory agencies like the US FDA will likely require rigorous testing for several years before Phase I (safety) clinical trials can begin in humans.

 

 Even given these challenges, the Jain Foundation thinks this approach is promising.  We are optimistic that, given time and the necessary research, an efficacious gene therapy approach specific to dysferlinopathy (LGMD2B/Miyoshi) can be developed and we are committed to helping move this process forward.  An important point to note regarding the application of gene therapy as a therapeutic option is that each individual needs to be genetically diagnosed by the identification of mutations in the dysferlin gene in order to be eligible for such a treatment.  If you are unsure whether or not you have been genetically diagnosed the Jain Foundation can help.  Please contact the Jain Foundation’s Director of Patient Relations, Sarah Shira, at or 425-882-1440 or click here for more information.

In their recent article, 1α25(OH)2-Vitamin D3 increases dysferlin expression in vitro and in a human clinical trial, Dr. Eduard Gallardo and his colleagues report that vitamin D3 has the ability to affect the production of the dysferlin protein.  This study was done on individuals that do not have a dysferlinopathy, but who have only one (of two) normal copy of the dysferlin gene.   Generally, a person with only one (of two) normal dysferlin gene makes approximately half the amount of dysferlin made by a person with two normal dysferlin genes.  In this study, when the researchers gave vitamin D3 to individuals with only one normal dysferlin gene, their expression of dysferlin increased.  Based on this data, the authors suggest that this increase in dysferlin could be beneficial to those individuals whose muscle disease is caused by mutations in the dysferlin gene, but who still make a small amount of dysferlin protein.  However, the increase in dysferlin was only evaluated in the blood, not the muscle, so it remains to be confirmed whether the increase in dysferlin can also occur in the muscle. While this information is interesting, a lot more research is needed before determining whether vitamin D3 supplementation would be beneficial in treating dysferlinopathy (LGMD2B/Miyoshi).

 

Vitamin D is an essential vitamin that is found in some foods like fish and fortified dairy products, and is also made by the body in response to exposure to sunlight.  Many people have a deficiency of Vitamin D without even knowing it.  Vitamin D deficiency can cause a bone disease called rickets in children, and can cause susceptibility to infectious diseases and cancer in adults. Vitamin D deficiency can be treated by vitamin supplementation, and also by an increase in casual skin exposure to the sunlight without sunscreen (while being careful not to get sunburned).   While, Vitamin D deficiency can be harmful, taking too much Vitamin D is toxic.  DO NOT start taking vitamin D supplements or change your vitamin D supplementation regimen without first talking with your doctor. 

 

Disclaimer:  The information contained in this communication is not intended to replace, and should not be interpreted or relied upon as, professional advice, whether medical or otherwise.  Please consult your health care professional for advice concerning the matter discussed herein.