Help Us Spread The Awareness of GNE Myopathy Worldwide - Do Not Underestimate The Power of One Small Action

                              

We envision a world where myopathies will not impede human aspirations, and where patients, and researchers collaborate on finding a cure for GNE Myopathy

We (patients and family members) are attempting to reach patients in all parts of the world who have been diagnosed with Gne-myopayhy  or are experiencing early signs of this disease. We are kindly asking for your help to translate this flyer into your language, print, and share with doctors,  family members, and other patients.   

**We currently have this flyer translated by patients, and other translators in Arabic, Chinese,French, Hindi, Italian, Farsi , German and Japanese with more languages to be added.  Please contact me if you need a flyer in your language and I will send it to you.

                                                   

                                                                  FLYER

    GNE Myopathy is known by different names such as Hereditary Inclusion Body Myopathy(HIBM), Nonaka Myopathy, Distal Myopathy with Rimmed Vacuoles (DMRV) or Quadriceps Sparing Myopathy and other names. The disease manifests itself in early adulthood. It begins with muscle weakness and ultimately makes the person totally disabled.  It is a recessive genetic disease which means that a person gets one defective copy of the GNE gene from each parent.  The normal GNE gene helps the body to make a sugar (sialic acid) important for muscle function and other activities.

We at GNE Myopathy International (GMI) are dedicated to helping patients with this disease, those who are recently diagnosed, or ones who are yet to be diagnosed, and assist them with finding the necessary resources to make their lives productive and fulfilling. It is very important to get diagnosed early as there are currently two medicines on trial for this disease.  For further details please visit our website (http://gne-myopathy.org/).

Some early signs and symptoms of GNE Myopathy:

*Foot drop with toes stubbing the ground

*Loss of balance and frequent falls

*Weakness in legs, arms, hands, hips, and shoulders

*Cramps in legs, weakness in the hamstrings

*Inability to run or climb stairs

*Difficulty standing on toes or heels

Please feel free to translate this page into your language and share with doctors and anyone with these symptoms.

Please contact specialists in your country, or email us at gne.myopathy@gmail.com

                       Please allow to post this in your clinic/community notice board.

                                 

Here is the Japanese version of the flyer - credit to Yoshio, S.

GNE ミオパチーは、遺伝性封入体ミオパチー(HIBM)、埜中ミオパチー、縁取り空胞を伴う遠位型ミオパチー(DMRV)、四頭筋スペアリング・ミオパチー(QSM)などの異なる名称で知られており、成人早期に顕在化する病気です。その症状は、最初に筋力の低下から始まり、最終的には寝たきりとなります。この病気は劣性遺伝病、すなわち患者は両親のそれぞれから受け継いだ GNE 遺伝子の欠陥因子が二つ揃った場合に起きる病気です。正常なGNE 遺伝子は、人体が筋機能やその他の活動にとって重要な糖分（シアル酸）の生成を助けるものです。

我々、 GNE ミオパチー・インターナショナル(GMI) の目的は、最近この病気と診断された患者、あるいは正確な診断を必要とする患者の救済に全力を尽くすことにあり、さらに患者が満たされ充実した人生を送れるために必要な情報源を見つけるための援助をすることにあります。

この病気には、２種類の薬が臨床試験中でありますから、早期に診断を受けることが非常に重要です。この詳しい情報は、ウェブサイトをご覧ください  (gne-myopathy.org).

 GNE ミオパチーの初期の症状と特徴:

*垂れ足（つま先が上がりにくく、つまずきやすい）

*バランスを失い転びやすい

*足、腕、腰、肩の力が弱くなる

*足の痙攣、膝の後ろの筋力が弱くなる

*走ること、階段を昇ることができない

*つま先や踵で立つのが困難

このような症状のある方、および医師にこれを見せてください。

地域の専門家、またはgne.myopathy@gmail.comにメールでご相談ください。

このパンフレットを診療所などの掲示板に貼らせてください。

Ultragenyx Announces Global Phase 3 Study of Aceneuramic Acid (Sialic Acid) for GNE Myopathy

Ultragenyx is launching Phase 3 trial of Sialic Acid tablets to treat GNE myopathy.  The name Sialic Acid  has now been changed to "aceneuramic acid" one of its multiple chemical names. Participants will be either on a placebo or on aceneuramic acid extended release  tablets(Ace-ER). This study is designed to recruit eighty patients worldwide.  Clinicaltrials.gov site as of this blog states "not  yet recruiting", however patients who are interested in participating may want to call the site in their respective country. The countries listed are the United Kingdom, United States, Canada.  I also see France, Italy, Israel,and Bulgaria I am unsure of the status of these countries.  Please refer to the  links for this posting from Ultragenyx, and the clinicaltrials.gov below.  Please feel free to contact me if you have any questions or need assistance.

http://www.ultragenyx.com/ht/a/GetDocumentAction/i/45418

Contact Ultragenyx Pharmaceutical Inc. Investors & Media Robert Anstey 844-758-7273 Ultragenyx Announces First Patient Enrolled in Global Phase 3 Study of Aceneuramic Acid (Sialic Acid) Extended Release in GNE Myopathy Novato, CA — May 28, 2015 —


https://clinicaltrials.gov/ct2/show/NCT02377921?term=hibm&rank=4

Contacts

Contact: Kim Mooney	415-483-8872	kmooney@ultragenyx.com

Locations

United States, California
University of California, Irvine	Not yet recruiting
Irvine, California, United States, 92697
Contact: Brian Minton    714-456-8520    bminton@uci.edu
Principal Investigator: Tahseen Mozaffar, MD
Canada, Ontario
McMaster University	Not yet recruiting
Hamilton, Ontario, Canada, L8N3Z5
Contact: Erin Hatcher    905-521-2100 x 76929    hatchere@hhsc.ca
Principal Investigator: Mark Tarnopolsky, MD
United Kingdom
The Newcastle upon Tyne Hospitals	Not yet recruiting
Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP
Contact: Oksana Pogoryelova, PhD    +44 (0) 191 2418640    Oksana.Pogoryelova@newcastle.ac.uk
Principal Investigator: Hanns Lochmuller, MD

Devices Currently Being Used by Persons with Gne Myopathy

The patients from our Gne-Myopathy support group on Facebook have listed the type of assistive devices they currently use.  These devices assist them in mobility, independence, and to maintain safety while maneuvering life's daily activities.We have summarized their experience, impression, and suggestions. It is possible that experience may vary from person to person using the same device. We want to graciously thank them for their input. This information could also be sourced at our website: gne-myopathy.org under the "Support Community" tab.

A number of companies (such as Ossur, Ottobock) make a variety of devices that are designed for people with different needs. There are also smaller companies which are able to customize some of the ready-made devices to suit individual needs.

 http://www.phatbraces.com/patients.phphttp://dynamicbracingsolutions.net/

Orthoses, Ankle Foot Orthoses (AFO’s), Braces

These equipment assist persons who have GNE-Myopathy with better stability, gait, balance, and help to lift up the toes.

Swedish AFO: These do not appear to restrict while walking or turning and or driving a car. There is a possibility that the experience may differ from people to people. It is important to get the right shoes with these. One can wear them with sketchers, trainers and converse, anything that comes up higher on the back of the heel. 
http://www.alimed.com/freedom-swedish-afo.html

Push Aequi Ankle Brace: This has been used during exercises and walking around the house. It can be worn over the socks and best results are obtained with closed shoes.

Toe Off Brace from Allard: It is quite comfortable and one can use it during driving. 
One of the patient, who uses this is 5'8” tall and is able to walk. She wears size medium as it comes up higher on her leg and gives added balance when standing still. One can climb steps with handrails and low incline ramps with these braces. The downsides are: they don't fit in all shoes/sneakers and all shoes need removable insoles. The foot plate cracks after six months, and one needs a cane or some assistance on steep inclines.

Ossur AFO Light: These have been found to be quite comfortable and it is easier to find shoes that fits these devices. 
http://www.ossur.com/.../ankle-foot-orthosis/afo-light

Walk-On: In general the experience has not been good during negotiating stairs, and for driving with these devices. One reason suggested by a patient is the experience of feeling restrained when one attempts to push down on the pedal. Patients find it difficult to climb stairs and negotiate inclines as these braces do not give enough support. On the other hand, some people have used these for many years. It does take some time to get one’s balance right as they feel unsteady with them at first because of the "spring" it adds to one’s step. If you do not use a cane or walker, you may want to use one just while your gait adjusts to the new braces.
 http://www.ottobockus.com/.../solutio.../ankle-brace-walkon/

Boxia Ankle Brace: It is also being used by patients and generally has been found useful for walking. https://www.chaneco.co.uk/orthotic-product.asp?prodId=324&specialoffer

OttobockDyna Ankle: It gives support but does not give the 'push' to clear the ground as other AFO's do.  http://www.ottobock.com/cps/rde/xbcr/ob_com_en/646A147-GB-01-1102w.pdf

Canes, Crutches,Walkers, Rollators, and Wheel Chairs
Some of these aids are highly useful in keeping people with GNE Myopathy mobile, and as independent as possible for them to carry on their daily activities. Again, experience vary from one individual to another, and one has to try out different ones to find out which would be the best. 
Many patients find using a walking stick helps them to walk safely. One patient finds a forearm crutch useful in walking on a level area. Another, found a palm grip walking stick more useful. It gives full support to the palm which helps in keeping hand and palm in alignment, and does not slip while walking. The stick comes customized for either left or right hand. The forearm crutch gives extra support to the elbow. 

Rollators: These can be highly useful for some specific activities, such as getting from a car to a class, or office. The patient is able to sit on the seat when tired and also can carry belongings in the basket. This rollator below is wide enough to accommodate the wider gait associated with GNE Myopathy. It gives added stability, balance, and helps one to safely walk longer. 

http://www.amazon.com/Cosco-Ability-Care-Traveler-Rollator/dp/B0008ENS98/ref=sr_1_cc_2?s=aps&ie=UTF8&qid=1431395663&sr=1-2-catcorr&keywords=cosco+travel+rollator

Wheelchair: These are used quite extensively by patients with different types of disability. Many people use these only for specific purpose, generally during travelling, sightseeing or shopping. Although, the wheelchairs can handle uneven path, it is difficult to use them on un-surfaced, and rough roads. There are two types of wheel chairs, manual, and electric/battery powered. Generally manual ones will require assistance for locomotion.

Lightweight and can be dismantled and fitted in a car. 
http://www.spinlife.com/Invacare-At'm-Take-Along-Travel/-Portable-Power-Wheelchair/spec.cfm?productID=73503

http://kdsmartchair.com/

Additional Assistance
A yoga belt has been found to be useful by a patient when she travels on planes or have to stay in a hotel. This helps to keep the knees together so they are not splaying out to touch other passengers. The yoga belt can also be useful to lift legs up if a hotel bed is higher than what one is used to.

It is advisable to consult a physio-therapist or suggestions in choosing the appropriate devices.  The scientific way is to analyse gait with and without different devices and choose one that gives you the best  result. Walking gait analysis is offered only in a few places that specializes in motor neuron disorders. 

Here are some centres and resources where gait analysis are being researched:

The Gait and Clinical Movement Analysis Society - The mission of GCMAS is to improve functional outcomes and quality of life for individuals with any movement disorder or at any age.

http://www.gcmas.org/about

European Gait analysis:
http://www.esmac.org/

This is a very informative blog site on gait analysis and lower limb bio mechanics.
http://wwrichard.net/blog/

A Summary of Current and Future Therapies For Gne Myopathy

This is a special report which has been written  by two members from the  gne-myopathy.org website.  They  have summarized various therapies that are currently being tried on patients, and other future therapies that may help patients with gne myopathy. This report is written in a concise and clear form that is easy to understand.  Please  address any query or comments  to the authors whose contact information is at the end of the report. This article could be found on gne-myopathy.org

SPECIAL REPORT 

Therapies for GNE Myopathy: Current Status and Future Prospects 
Summary 

A number of approaches for development of a cure for GNE myopathy are currently available. These therapeutic possibilities are being developed for a large number of different diseases, including genetic disorders. None of these have reached a stage where they are ready to be used by patients. Initial studies do indicate that all therapeutic approaches appear to be safe and non toxic, suggesting that these therapeutic platforms can be developed for treatment of different diseases. Sialic acid supplementation as a cure for GNE myopathy is in extended phase two trial and is likely to be the fastest to reach the market. The National Institutes of Health in Bethesda, Maryland, U.S.A. has just started recruiting patients for phase one/phase two trial of Dex-M74, a ManNac substrate.
• More...
  • 1. Gene Therapy:

    HIBM or GNE myopathy is caused by a defective GNE gene that has reduced activity, as a result of which the level of sialic acid, an essential sugar, is low in cells. For unknown reasons physiological effect is more pronounced in muscle cells leading to progressive muscle degeneration. Mutations in the GNE gene are responsible for this defect. Gene therapy approaches offer a possibility of delivering a corrected copy of the gene in muscle cells so that active GNE protein is made and sialic acid levels are restored. Gene delivery can be done in many ways. However, the first two approaches are more common.
        a. Viruses such as adeno associated virus (AAV), lentivirus, etc. are being considered as vehicles for carrying the healthy DNA to the                   muscle cells to correct the affected gene.
        b. Use of lipids in which the DNA is encapsulated.
        c. Naked DNA can also be delivered, but may be amenable to degradation.
        d. Messenger RNA (mRNA) therapy which uses mRNA of the gene in place of DNA. 
    
    A brief description of these approaches is given below. So far FDA has not approved any gene therapy product for patient treatment. Most of the trials with genetic diseases are either phase I or phase I/II combined trials. Many of these have been completed, but progression to phase III trials does not seem to have happened. From the available information only one potential gene therapy treatment seems to have reached phase III. This is for  “Leber's congenital amaurosis”, a rare eye disease. So far no gene therapy trial has been announced for GNE. If safety and efficacy of the vectors are proven favourably in ongoing trials mentioned above, particularly for muscle diseases in human trials, and HIBM in animal models, then it should not take more than one to two years before gene therapy could be tried for GNE patients.
    
    Viruses as vector for gene therapy: AAV is turning out to be a front runner because of multiple reasons, such as its ability to enter into, and function in non dividing cells. as iIt shows low immune response, low integration rates and is generally -non pathogenic. On the other hand lentiviruses do lead to multiple integrations in host DNA that can cause some problems. Size of the DNA that can be packaged into the virus to making virus particles in the test tube in a way that they can enter cells just like normal viruses, but will not cause disease) is also a limiting factor ; for example, AAVs can package only 4-5 kb DNA. That is why it is very difficult to pack the whole gene of DMD in one virus as the gene is very large Alternate methods are being developed for packaging fragments and assembling inside cells (please see for details http://www.genetherapynet.com/viral-vectors.html). Genomic version of GNE gene is about 62 kb and mRNA (the part that has information about making proteins) is about 5.1 kb. Open reading frame of GNE (absolutely minimal part of the gene which with some help can make GNE protein in cells) is 2.2 kb, which is a size suitable for packaging in AAV vector. Thus packing should not a problem in the case of GNE. Data is required to check packing efficiency of GNE in different versions of AAV vectors.
    
    One of the major issues in using viral vector is the need for giving multiple injections, which could trigger potentially undesirable immune response against the viral vector. Vectors are being designed where immune response is negligible so that the gene could be delivered a number of times. AAV has been modified in a recent Phase I trial for muscular dystrophy to further reduce its immune response and enhance ability to make functional protein in muscle cells (AAV vector 2.5). This vector was well tolerated and could deliver functional proteins (Bowles et al. Molecular Therapy, Vol 20, page 443, 2012). The trial was conducted by injecting into muscles of one side of the body and using the other side as control. AAV2.5 vector appears to be much more advanced than the patent filed by Israel GNE group.
    
    Use of lipids: Cationic lipids are thought to be good carriers as they protect the DNA during delivery and are efficiently taken up by cells. However, to be most effective in gene therapy the DNA needs to reach the nucleus of the cell, which is the inner compartment. While viral vectors deliver the DNA to the nucleus, lipids deliver it to the outer compartment- the cytoplasm. Lipids are also thought to be more toxic. Lipid carrier was used in a study with a single GNE myopathy patient (Nemunaitis et al. Human Gene Therapy vol 22, page 1331, 2011). One intra-muscular and one intra-venous injection was given using “lipoplex”, a lipid mixture. Gene delivery did take place, but it is not clear as to how many cells received the gene. Better cationic lipids have now been developed which could be more effective. Unfortunately, no animal data seems to be available to indicate how efficiently the vector is taken up by different cells. Most of the information is available as conference posters where no details are given.
    
    Plasmid DNA: Instead of viral vectors it is possible to use naked plasmid DNAs containing the desired gene under the control of suitable promoters which would allow the gene to be expressed into mRNA. These can be delivered to the tissues using specific approaches (such as US-1274 http://www.wiley.com/legacy/wileychi/genmed/clinical/), either naked or suitably encapsulated by lipids or other nanoparticle-based formulations. The advantage of this system is that it is easy to produce the DNA and scale up. However sometimes double stranded DNA does stimulate innate immune response.
    mRNA therapy: Information in the gene is transcribed into mRNA which then makes the protein using cellular machinery. Therefore, instead of using DNA it is possible to correct the defect by making the corrected mRNA in the test tube and sending it into the cells. Since mRNA acts in the cytoplasm, and does not need to go to the nucleus, lipid carriers are better suited for mRNA delivery. This is a promising new approach and a lot of work is going on to optimize this approach; for example mRNA is being modified to increase its stability in the body. Trials are planned in the area of muscular dystrophy to, repair damaged heart muscle, and in some vaccine trials to stimulat immunity ( Some examples, Kormann et al. Nature Biotechnology, vol 29, page 154, 2011: Wang et al. Molecular Therapy Vol 21, page 358, 2013; Zangi et al. Nature Biotechnology Vol 31, page 358, 2013 ). mRNAs have several advantages over plasmid DNA. They are relatively inert towards the immune system, and being short-lived are less likely to have adverse effects. However they will need to be administered to the patient on a continuous basis.
    mRNAs are being tested as vaccine candidates for preventing/treating cancer and other diseases http://modernatx.com/about-us, http://www.curevac.com/). These approaches are at different phases of clinical trials. FDA approval may be granted soon for mRNA as vaccine/therapy for cancer (phase II trials are currently being done). There is a major attempt to use mRNA/short RNA segments to treat DMD by preventing exon skipping (http://www.prosensa.eu/technology-and-products/exon-skipping). Full length mRNA therapy for genetic disorders has not yet been attempted. However, developments in this technology and analysis of safety features will be useful for other applications, including treatment of GNE myopathy.
    In addition, methods are being developed to correct gene mutations using oligonucleotides (short DNA chains). Most of the applications involve either correction of a mutation in a test tube, and then transferring the corrected cells, or exon skipping of a specific type of mutation. There is no literature to suggest that it may be applicable in GNE myopathy. However, some success stories are there. A chimeric RNA/DNA oligo was able to repair a genetic defect in a canine model of myotubular myopathy (Childers et al. Science Translation MedicineVol 6, Jan 22, 2014).
    
    2.Stem cells:
    In an adult, most differentiated cells (such as muscle, brain, liver) do not multiply and their proliferating ability is restricted. However, these tissues do have a small number of dividing cells (stem cells) that have the ability to multiply and get differentiated into the respective tissue cells. These cells, though small in number, play a major role in tissue repair and regeneration. For therapeutic purposes one needs a larger number of stem cells. Fertilized embryos are a great source of stem cells (known as embryonic stem cells or ES cells), which under suitable conditions can convert into any cell type of the body. Since these can be cultivated and stored as ES cells, it is possible that these can be used for regeneration of any tissue. However, due to ethical reasons, and a ban on work with such cells, research has not progressed significantly.
    
    A new Nobel Prize-winning technology, known as induced pluripotent stem cells (iPS) allows generation of stem cells from cells of an adult individual, where ethical concerns are fewer. Unlike ES cells, these cells do not have the potential to differentiate into all cell types. Nevertheless, they do have the ability to get converted into some of the important cell types, such as muscle and neuronal cells. Some of the technical problems are to get sufficient number of iPS cells for use in therapy and to convert them into the desired cell type with high frequency. Both these problems are being addressed, and a recent report from Harvard University announced significant improvement in the efficiency of iPS cell formation (http://hsci.harvard.edu/news/hsci-lab-explores-more-efficient-ways-generate-ips-cells, also Mali et al. Stem Cells Vol 26, page 1998, 2008). In this system skin cells from patients are taken and converted into iPS cells using a cocktail of molecules. iPS cells proliferate and can theoretically be kept in storage forever. Generating patient specific iPS cells eliminates the problem of rejection (like tissue grafting) inherent if cells are taken from unrelated individuals. However, there is still the problem of defective gene present in these cells since they came from the patient's own tissue. In a recent breakthrough, Japanese scientists managed to correct the genetic defect of muscular dystrophy in iPS cells. The corrected cells were then converted into muscle cells that showed highlevel expression of the corrected gene (http://www.theguardian.com/science/2014/nov/26/muscular-dystrophy-therapy-breakthrough). In this regard the first clinical trial has started in Japan, where scientists are going to check efficacy and safety of human iPS cells.
    
    Bone marrow is also a good source for stem cells. However, its ability to transform efficiently into non blood cells is not very clear. Nevertheless, bone marrow cells are easier to handle and manipulate. Therefore, these are quite popular among stem cell biologists who are interested in developing therapies. Many clinical trials are starting to use these cells in DMD. Similar stem cells are also present in umbilical cord blood and some of the issues raised in relation to bone marrow cells also apply here. The hope is for these to show favourable results, though in both cases no positive result has been seen in non-blood disorders.
    One of the major concerns about stem cells is that these can easily form cancer cells. Whether iPS cells or different versions of stem cells will show similar propensity for cancer, is not clear as yet. The studies thus far have not shown significant safety/toxicity problems.
    
    3.Sialic acid replacement:
    One of the features displayed by patients with GNE myopathy is reduced level of free and conjugated sialic acid in tissue and blood. In animal models it has been seen that supplementation with sialic acid or its precursor N-Acetyl mannosamine (ManNAc) restores sialic acid levels and suppresses disease phenotype. This has prompted development of therapeutics based on these molecules. The problem of sialic acid is that it gets cleared quickly from the system, that is, it is in circulation for a short time and only a small fraction is taken up by the cells due to its poor uptake. One of the solutions is to release it slowly in the intestine so that there is a sustained level of the molecule in circulation. The problem of uptake is still there even in slow release system. On the other hand, ManNAc is taken up by cells more readily, but has to be converted to sialic acid.
    Another approach is to use modified sialic acid (such as an ester) which neutralizes the acidic charge of sialic acid. Because sialic acid has an acidic charge it has poor uptake, while the ester has a better absorptive capacity since the charge is neutralized. Once inside the cell the sialic acid ester is expected to be targeted by catalysts like esterases which break the ester bond and generate free sialic acid. This system is very well known and there are numerous examples of its use in cellular systems (for examplehttp://www.ncbi.nlm.nih.gov/pubmed/17307252, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC396923/pdf/plntphys00191-0141.pdf).There is no reason why it should not work for GNE myopathy. Therefore, a slow release formulation of sialic acid ester could be a good treatment option. Ultragenyx has filed for a patent on modified sialic acid synthesis and its use in HIBM therapy (US patent application 20150038693). Analysis of the patent showed that there is lot of possibility of generating new molecules here. However, toxicology and safety studies need to be done as some of the esters are not naturally occurring molecules. There is a possibility that if esters are successful, the total dosage required may come down.
    
    A way forward: Looking Into the Future For A Cure 
    We can think of a number of different strategies for developing a cure for GNE myopathy. We have to realise that some of the technology platforms discussed in this article (gene therapy and , stem cells) may not be available in ready-to-use form very soon. We have to wait for phase two and/or phase three results of trials with these technologies in other diseases. Particularly, we have to see the safety and toxicity results. Safety and toxicity studies using normal animals are relatively easy, and to save costs these studies could be outsourced to an organization in Delhi or elsewhere in India. Obtaining animal model of GNE myopathy is an issue. However, there are many companies that make these models as per individual requirement, and given the funds, we could generate the animal models commercially. The problem is that we need to find and carefully select experienced people to carry out efficacy studies. For example, measurement of muscle strength in mice requires special expertise.
    
    Ideally, gene-corrected autologous iPS cells (from respective patients) appear to be the best choice for long term cure. This technology has been developed in Kyoto and published in a paper last year. If Nishino’s group (who is a pioneer in GNE) can work with the Kyoto group for GNE myopathy we may be able to see some results sooner., HLA- matched heterologous (from different person) iPS cells also appear to be a possibility. The cost of treatment for heterologous system may be much lower. Since the cells can be prepared before, the amount of time for treatment may also be less. One issue is rejection of these cells, similar to what we see in organ grafts. In an ongoing trial in Europe heterologous stem cells seem to give long term benefit to heart patients (http://rt.com/news/228283-spain-heart-stem-cells/).
    
    Among all gene therapy methods, mRNA delivery appears to be the best choice at this point, since it is likely to have the least side effects. There is a company that can make this material on order., If we get access to animal models, and can generate funding, it could be possible to test this method.
    Finally, we can seriously think of modified forms of sialic acid in slow release formulation. India has well trained competent chemists, and its chemical industry has expertise to make any compound under GMP conditions. We can approach them for our specific requirement. These could then be tested for toxicity..-
    Sudha Bhattacharya sbjnu110@gmail.com
    Alok Bhattacharya alok.bhattacharya@gmail.com