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| Getting ready for the Gala |
Thanks to the efforts and generosity of over five hundred and thirty donors, patients, scientists, and industry professionals the Neuromuscular Disease Foundation (NDF) has raised a total of $2.5 M in donations and pledges towards a matching grant. On Sunday November 17, 2019 the NDF held its second annual Arts Gala at the Skirball Cultural Center in Los Angeles, California, U.S.A. A gallery of beautiful photos of the Gala could be viewed here.
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| Skirball Cultural Center Setting up for the Gala |
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| GNEM Researchers on Stage |
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| Scientific Advancement Awardees |
Dr. N. Carrillo from the National Institutes of Health (NIH), M. Minarich, CEO of Leadiant Biosciences and their team received the 2019 NDF Scientific Advancement Award for their work on ManNAc, a promising replacement therapy for those with GNEM. Additionally, the NDF presented five patients Maya D., (Israel), Mona P., (U.K), Kelly M., (Taiwan and China), Amy C., (USA), and Tara V. (USA) with "All-Star" awards for various impactful work these dedicated patient advocates are involved with globally. The Etebars also were acknowledged for their dedication to raising funds with NDF's 2019 Philanthropy Award.
In addition to the Gala, the NDF held an International Scientific Consortium Meeting on Monday November 18, 2019, at the Marriott Hotel in Los Angeles, California USA. More than thirty researchers and doctors came from different parts of the world to share, discuss, and present their data and projects. These esteemed researchers are currently exploring various mouse models, substrates, vectors and re-analyzing patterns and data that may lead to a potential cure and or treatment for GNEM.
This special Scientific Consortium Meeting was open to patients, observers, and others with vested interest. These researchers came together to examine, discuss research projects and findings, and develop an action plan for how to move forward quickly with a cure for the patients. Here is a summary of many of the presentations.
Disclaimer: I am a GNEM patient and felt humbled and privileged to be present at this fascinating and deep learning event. I am writing based on my understanding of what I heard, and I may have certain inadvertent inaccuracies in my understanding.
1. Dr. Carrillo from the NIH spoke on the clinical trial for Phase 3 ManNAc. With ManNAc trial phases 1/2 (tested for safety and tolerability) they observed that ManNAc was processed into CMP Sialic Acid and enters into the cells to repair the pathway. The longer a patient is uses ManNAc the more it increases stabilization of the GNE gene and has the potential to restore the pathway. Additionally, they are learning important information from the Natural History study which was started in 2011 and is ongoing, which will help to show a disease progression model The NIH also has a large biobank of GNE samples which they would be willing to share with other GNEM researchers. The Phase 3 ManNAc trial is slated to start in the first quarter of 2020. Patients who have been using either Sialic Acid or ManNAc for a year prior to the start of the trial will not be eligible.
2. Dr. M. Huizing from the NIH presented evidence for the various steps of ManNAc converting into CMP sialic acid and the manner in which it enters and absorbs into the cells.
3. Dr. Darvish, a GNEM patient as well, and the CEO of Orphina presented a treatment design model (H001) that he and his team has been working on for GNEM. His team claims that they have completed safety testing on small as well as large animals. This treatment would use a non-viral supercoiled plasmid vector, repeat dosing is possible if once is not sufficient, and it would require vascular isolation of the limbs (arms and legs) with a tourniquet. Dr. Darvish further claims that this treatment shows an increase in muscle fibers with lower immune response than the standard gene therapy.
4. Dr. P. Martin from Martin Lab, Children's Hospital, Columbus, OH. His lab focuses on the glycosylation in synapse formation and research on muscular dystrophy. He presented information on aav vector, mediated micro RNA, and intimated that we don't have a reliable animal model nor proof of concept in an animal model.
5. Dr. M. Lek and A. Lek (both on the NDF SAC board) discussed that their lab are conducting analysis on the samples they took from patients and families during various sponsored NDF Symposiums. The findings will be shared with respective patients in due course. Moreover, the Whole Genome Sequencing done by Perkin Elmer will examine if there are gene/gene interaction of which this information will be available in the future.
6. Dr. A. Bhattarcharya from World Without GNEM (WWGM), New Delhi, India, presented information on their effort to further gene therapy. Their organization gave out two grants earlier this year to researchers to explore cutting edge scientific projects that will expedite treatments for GNEM. Dr. Bhattarcharya postulates that supplementing small molecules (endogenous source) may activate and restore mutant protein function at a molecular level. An Indian company has already developed aav vectors.
7. Dr. O. Pogoryelova and Dr. Lochmuller from Lochmuller Lab, Canada presented on the "Newcastle" GNEM patient registry based on the Functional Activity Scale (FAS) and they argue that we need to "harmonize" all the registries.
8. Dr. S. Rosenbaum, Hadassah, Israel discussed about aav vector and that a stable mouse model is proving to be complicated. Dr. Rosenbaum stated that we have no robust mouse model with the muscle phenotype, that the GNE gene is complex in the manner in which it attaches to the protein, and the GNE gene is responsible for two enzymatic activities. She further stated that she is currently working on aav platform to develop a vector and hypothesized that with systemic injections SA may enter the cells. She continued on to say we that have no real human proof of concept as of yet.
9. Dr. W. Yoshioka and also a GNEM patient from Japan explained a project that her team is working on to isolate Sialic Acid from salivary glands, as saliva contains conjugated SA which may be a potential treatment. They are in very early stages of this exploratory work.
My Take Away
Joseph Campbell from the Power of Myth:
"People say that what we're seeking is a meaning for life. I don't think that's we're really seeking. I think that what we're seeking is an experience of being alive, so that our life experiences on the purely physical plane will have resonances within our own innermost being and reality, so that we actually feel the rapture of being alive."
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| All Star Awardees |
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| Philanthropy Awardees |
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| Scientific Consortium Meeting |
1. Dr. Carrillo from the NIH spoke on the clinical trial for Phase 3 ManNAc. With ManNAc trial phases 1/2 (tested for safety and tolerability) they observed that ManNAc was processed into CMP Sialic Acid and enters into the cells to repair the pathway. The longer a patient is uses ManNAc the more it increases stabilization of the GNE gene and has the potential to restore the pathway. Additionally, they are learning important information from the Natural History study which was started in 2011 and is ongoing, which will help to show a disease progression model The NIH also has a large biobank of GNE samples which they would be willing to share with other GNEM researchers. The Phase 3 ManNAc trial is slated to start in the first quarter of 2020. Patients who have been using either Sialic Acid or ManNAc for a year prior to the start of the trial will not be eligible.
2. Dr. M. Huizing from the NIH presented evidence for the various steps of ManNAc converting into CMP sialic acid and the manner in which it enters and absorbs into the cells.
3. Dr. Darvish, a GNEM patient as well, and the CEO of Orphina presented a treatment design model (H001) that he and his team has been working on for GNEM. His team claims that they have completed safety testing on small as well as large animals. This treatment would use a non-viral supercoiled plasmid vector, repeat dosing is possible if once is not sufficient, and it would require vascular isolation of the limbs (arms and legs) with a tourniquet. Dr. Darvish further claims that this treatment shows an increase in muscle fibers with lower immune response than the standard gene therapy.
4. Dr. P. Martin from Martin Lab, Children's Hospital, Columbus, OH. His lab focuses on the glycosylation in synapse formation and research on muscular dystrophy. He presented information on aav vector, mediated micro RNA, and intimated that we don't have a reliable animal model nor proof of concept in an animal model.
5. Dr. M. Lek and A. Lek (both on the NDF SAC board) discussed that their lab are conducting analysis on the samples they took from patients and families during various sponsored NDF Symposiums. The findings will be shared with respective patients in due course. Moreover, the Whole Genome Sequencing done by Perkin Elmer will examine if there are gene/gene interaction of which this information will be available in the future.
6. Dr. A. Bhattarcharya from World Without GNEM (WWGM), New Delhi, India, presented information on their effort to further gene therapy. Their organization gave out two grants earlier this year to researchers to explore cutting edge scientific projects that will expedite treatments for GNEM. Dr. Bhattarcharya postulates that supplementing small molecules (endogenous source) may activate and restore mutant protein function at a molecular level. An Indian company has already developed aav vectors.
7. Dr. O. Pogoryelova and Dr. Lochmuller from Lochmuller Lab, Canada presented on the "Newcastle" GNEM patient registry based on the Functional Activity Scale (FAS) and they argue that we need to "harmonize" all the registries.
8. Dr. S. Rosenbaum, Hadassah, Israel discussed about aav vector and that a stable mouse model is proving to be complicated. Dr. Rosenbaum stated that we have no robust mouse model with the muscle phenotype, that the GNE gene is complex in the manner in which it attaches to the protein, and the GNE gene is responsible for two enzymatic activities. She further stated that she is currently working on aav platform to develop a vector and hypothesized that with systemic injections SA may enter the cells. She continued on to say we that have no real human proof of concept as of yet.
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| Drs. K. Crowe and W. Yoshioka |
10. Dr. N. Weisleder, Ohio State University, Columbus, OH, mentioned that his lab studies the various aspects of skeletal muscles and how repair could take place to damaged vacuoles/membranes.
Status of NDF Gene Therapy
The NDF's absolute focus is to expedite a cure for GNEM and has therefore engaged reknowned researchers/scientists worldwide to this effect. Many of the above mentioned research have in some part received grants or will receive grants from NDF. For a brief video on NDF's strategy on gene therapy please see this link: https://www.youtube.com/watch?time_continue=4&v=LV19xElHBGg&feature=emb_logo
The NDF's absolute focus is to expedite a cure for GNEM and has therefore engaged reknowned researchers/scientists worldwide to this effect. Many of the above mentioned research have in some part received grants or will receive grants from NDF. For a brief video on NDF's strategy on gene therapy please see this link: https://www.youtube.com/watch?time_continue=4&v=LV19xElHBGg&feature=emb_logo
Disclaimer: These are presentations made by participants at the NDF Scientific Consortium Meeting on GNE Myopathy on 11/18/19 and some have not been peer reviewed. NDF does not take a position as to whether the results are valid or reproducible.
I felt fortunate to be in the room, on the sidelines of this captivating Scientific Consortium Meeting, and to listen to these brilliant dedicated researchers discussing, engaging, arguing, and wrestling with their findings and potential experiments. As I sat there absorbed trying to make sense of the many medical and technical discussions, I couldn't help but feel an overwhelming sense of joy and deep pride knowing that these visionaries are on our side, fighting for us. All of them are dedicated towards curing our disease. We have many extraordinary "giants" working on GNEM and this gives me peace of mind. I also know that research, clinical trials, and finding cures take an incredible amount of time and diligence. That is the nature of experiments. But I am heartened by these doctors' and scientists' willingness to interact with the people whose suffering they are trying to alleviate. They have the courage to see us, not just as test subjects, but human beings in a fight for our lives. For that I am grateful.
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| Tune in to NDF's Podcast Series |
Upcoming Events
1) Our monthly virtual Huddle 'Preparing to Expect the Unexpected" coming up on December 7. Register at this link: https://www.facebook.com/NDF.HIBM/https://donate.curehibm.org/event/ndfs-patient-huddle-december-2019/e2572482)
2) ManNAc trial- to begin early 2020. Monitor site: https://clinicaltrials.gov/ clinicaltrials.gov
3) The NDF will debut a new monthly podcast series starting in 2020.The podcast will be posted at this link: https://curehibm.org/news-events/podcasts.html
"People say that what we're seeking is a meaning for life. I don't think that's we're really seeking. I think that what we're seeking is an experience of being alive, so that our life experiences on the purely physical plane will have resonances within our own innermost being and reality, so that we actually feel the rapture of being alive."
