tara

tara
Meeting my Congressman

Sunday, February 18, 2018

Living with a Rare Muscle Disease: A Turkish Woman Rises Above Disability, Poverty, and Gender Bias, Rare Disease Happenings Within the GNEM Community

To commemorate Rare Disease Month, observed world-wide every February, I want to highlight a Turkish woman who lives and thrives with a rare muscle disease in spite of poverty and disability.  I was touched by her undaunted spirit , and her perseverance in becoming a productive member of society while facing obstacles that would stop most people.  Fatma is no ordinary person.  Here is her story.
I am Fatma and was born in rural Turkey into a family of eight other siblings. From a very early stage in my life I was aware that I was suffering from a muscular disease namely Limb Girdle Muscular Dystrophy  (LGMD 2E) this was when I was in primary school. My family was not aware of the support they could get for their children because of their socioeconomic level in society.  I also did not know if there was any  assistance available to help me increase my opportunities.

A  low-income family living in an underdeveloped society, and having a disabled daughter in this society, was truly a monumental challenge for my family.  Nevertheless, this daughter had dreams of becoming free, constructive,  and becoming a “fully functioning human being.”  My dreams seemed impossible, and so I realize that I could not accomplish these dreams on my own resources. I know from my experience that everything begins with creative imagination. I think that I remained true to my dreams.

Some questions arose for me such as how could my dreams become real in a society where women were second class citizens who have no right to an education. Maybe I wanted was impossible as a disabled girl since her society did not permit girls to have an education.

When I finished high school, I brought together two friends to help me accomplish my dreams.  These two friends (my sister and my brother) shared with me the same fate, this muscle disease. I knew I could not go backwards, nor give up because I need to be a strong example for my siblings who also have this disease. 
I experienced many insults in primary and high school  nevertheless I persevered to graduate from both.  I thought about attending university but realized that there was no accessible university for people like me.  My family did not have the financial means to support higher education for me. Against all odds, I won  a place in the Economics Department at a university but then found out that I could not ascend the stairs of the building  to take the exams.

Another one of my dreams was to have a job because I knew I would then be economically independent and maybe I would be more creative. I went on to register at an employment agency after I finished high school; however I waited for years for a job but could not find one.  I even wrote to a Tatvan member of parliament with hopes but only received a response that I should be patient.  I waited for years to hear more from this member, but it soon became clear to me that this member did not understand the struggle I had from living in my disabled body. 

During this time I started to think about how other persons who viewed disable persons, and how insensitive, un-sympathetic, and ignorant society can be to us.  It became clear to me that I must then fight with all my power about the difficulties of living in a disabled body.  To me, it seemed that no matter how hard I fought, nobody heard or remotely understood me.  Not only do I live with my disability, my parents, family, and some close relatives also live to some extent in my reality. Sometimes, I feel as though I have heavy shackles on my feet.  There are many obstacles to overcome when you are disabled, for example, when my Math teacher said, “what happens when you are educated,” when the  Member of Parliament won Parliament with my vote who had the same perspective as my math teacher.

Many  people said that it is better if I stayed at home with my family and accept my fate as a disabled person.  I struggle with people who tell me that I should not work, should not go to the university, or should not do this or that.  That would be too many rejections for me to accept because I saw myself as a “functioning human being.” These rejections made my existence very difficult, yet I continued to dream.  According to me, being human, loving, being creative, and being able to work  facilitate human-ness; in fact, these life conditions are very liberating and I want to experience these indispensable qualities of life.

I noticed it is knowledge that I am drawn to by reading books since people avoid my friendship. I find the answers to my challenges in sociology, psychology, literature, and philosophy. Descartes says, “Reading  good books is like talking to the best persons of the past centuries”.  I learned that there was a connection between sensuality and sensibility when we learn more. I noticed that learning was endless, and it illuminates the senses which helped me to state my opinions and ideas.  Learning has empowered me as a disabled woman.  Because of this reality, reading, learning, and loving unconditionally  in any situation, no matter whatever happens are indispensable to me.

My journey as a disabled woman living in rural Turkey consisted of societal norms such as I could not be free to be myself physically because of the stigma associated with disabled individuals. My brain and heart flutter with freedom, the freedom no one can see; however, I feel and know this freedom.  I am not unhappy with my condition now since I as give un-conditional love and affection to everyone I meet.
I am now 45 years old, I lost my brother when I was a child, and I knew that I would be dependent on a wheelchair, like my brother, in the future.  Only that I would be in a wheelchair, I did not know anything else about my disease.  In the earlier years when there was no internet, there was only one way through which I could get information.  It was a journal  named "Hope and Life,” published  every three months by the Neuromuscular Disorders Association of Turkey. My sister, my brother, and I eagerly looked forward to reading this journal hoping to see new developments for our disease.  We met with frustration every time as the journal failed to report on any new developments for us.  We felt helpless.  Finally, in 1992 I went to Istanbul to learn more about our disease.
I remembered that day as I traveled hundreds of kilometers. I talked with my doctor for a few minutes; then he took a sample of my blood for analysis and further told me that I should get a biopsy soon.  I wanted to ask  many questions, but my doctor told me, “My dear Fatma, I have no time.”

I returned to Istanbul very many times for biopsies. I did not hear back about the results of my biopsies.  Years later I learned that the Laboratory of Çapa Medical Faculty Hospital was not equipped to test for my disease. Our doctors did not have the tools to diagnose many types of muscular diseases in Turkey at that time. Unfortunately, there are very few specialists who thoroughly understand the  different types of muscular diseases in Turkey. I lost my two brothers because of wrong treatments, ill-equipped doctors, and lack of basic equipment such as a BIPAP machine.  Also there was no proper Intensive Care Unit at the State Hospital in Tatvan.

The majority in our society cannot understand the scientific field and what it is like to live a quality and independent life. For patients to live independently is also big obstacle for many patients and their families.  Many patients, because of lack of knowledge, are unable to follow the instructions given to them by the specialists. For that reason I could not rescue my brother, who had respiratory troubles.  He was 30 years old, and like me he had many dreams but in the end I lost him.

Because of my experience in living with a muscle disease, I have dedicated my life to help those with muscular diseases. I now work for  the Board of the Muscle Disorders Association of Turkey.  I feel desperate every time I receive a phone call from a patient’s family and hear that they are in the Intensive Care Unit because I know the results that they will experience.

From living and learning here is what I have observed about the The Plight of People Living with Muscular Disease in Tatvan, Turkey:
Muscular dystrophy patients cannot obtain the knowledge to live a more qualified and humane life. Many are poor, cannot read, and are unable to leave their homes. They cannot receive basic medical help or any physical therapy they the would especially need.  All these basic needs should be solved effortlessly within a social state but it is not the case in Turkey.  Most of these patients are unemployed, although they have made all the effort that was in their power for many years.

For now, some rights that already were established for those with disabilities were taken back silently. For example, three months of financial assistance to thousands who are disabled were discontinued abruptly.  I think my turn will also come soon. We are mostly society that believes in fate.

There are very few neuromuscular disease doctors in Turkey.  Additionally, it is very difficult for patients to contact a specialist to learn more about their disease. Most patients do not have knowledge about their disease; they traveled from very far and then wait for hours in front of the poli-clinic, and then are told that there is no treatment.  Most return home with despair, beaten down, depressed, and hopeless.
 Patients who have financial means, however, and have a little bit knowledge try to learn more about their disease, yet they can not get sufficient knowledge. Patients in Turkey need to live as independently as possible and need to get appropriate support and knowledge about neurology, cardiology, physiotherapy, genetics, orthopedics, dietetics, and finally, psychological help.
You may contact Fatma here for the Turkish version of her story.  



Happenings in the GNEM Community:
1.  The Neuromuscular Disease Foundation (NDF) has launched a page "Rare Reality" on their website where GNEM patients are encouraged to share their story, here is the link.

2.  GNE Myopathy International (GMI) has recently  conducted a 2 day conference on the Perspectives on GNE Myopathy, for updates check here.  http://gne-myopathy.org/

Friday, January 5, 2018

A Look Back at 2017, Moving Onward with Hopes for an Effective Therapy, GNE Myopathy International to Host a Conference in New Delhi, India



Dear friends, family and readers:
To keep me motivated, engaged, and invested in managing my physical condition, I usually delve into medical journals, articles, and related information. Recently, a researcher suggested that I study a very timely and fascinating book entitled "The Patient Will See You Now," by Eric Topol.  
Mr Topol states, "When you put together open medicine, open science, open access, open source, and open data-Open-all sorts of new channels of research activity become available, and existing ones become exponentially more powerful" (p.211).  I find this quote quite befitting  for the strides we are making in our GNEM community, even though  we may have had a minor setback with the termination of Silac Acid-ER trial, it has also opened more doors to us for further research into the gene such as the global effort being led by the Neuromuscular Disease Foundation (NDF). The NDF is now collaborating with Perkin Elmer to conduct Whole Genome Sequencing (WGS) on 100 GNEM patients.  For additional information on this refer to:  Link for the Press Release


  
The NDF has set the stage for exponential growth in 2018 such as spearheading a Scientific Consortium through which scientists from around the world would be able to share and collaborate on GNEM research, gene therapy (which) is in the "toxicology study" stage, and Whole Genome Sequencing. 
In addition, the NDF Symposium in the summer of 2017 has set into motion a global network of patients who are certified GNE Myopathy advocates. These dedicated advocates are prepared to bring programs to patients and their families in their respective countries.Their intention is to bring GNEM patients together, disseminate information about GNEM, and find un-diagnosed patients. The certified advocates work as outreach to patients and families assisting them with finding appropriate resources. These advocates host GNEM Patient Days in their home countries. So far, Patient Days have been celebrated in Israel, Italy, and Korea. There are more of these events planned for 2018  in the United Kingdom, Turkey, and other countries. We are inspired as patients and continue to tip the scale by finding new patients. This is what is needed to attract more attention to GNEM.

Following the theme of "exponential growth", GNE Myopathy International  (GMI) will start out 2018 by hosting a two-day ground-breaking conference on the "Perspectives in GNE Myopathy"  This conference is a first of its kind for a rare disease to be held in New Delhi, India, on February 16 and 17, 2018.  Many known GNE Myopathy researchers, scientists, and doctors will be presenting at this conference. All GNEM patients and families are invited to attend this conference. Based on the population of India,one would assume that there are yet many undiagnosed patients unknown to doctors. With this conference the hope is to attract more attention to GNE Myopathy and to build a strong and cohesive patient community to take us to a step closer towards a treatment for GNEM.
Please refer to this link for registration and the programme.
** I urge everyone who is able to, to attend this conference. This is your chance to meet directly with the researchers who are studying our disease.

GNE Myopathy International continues to offer their educational webinar series  based on what interests GNEM patients.  Here is a link to the webinars that GNE Myopathy International has conducted.   Please feel free to suggest topics for future webinars at:  http://gne-myopathy.org/contact_us

NIH National Human Genome Research Institute
ManNAC 
The National Institutes of Health (NIH) recently completed Phase 2 trial using ManNAc and will be recruiting patients for Phase 3 trial in 2018.  Monitor this link for when the trial will start.  NIH ManNAc Site.

An article on the Characterization of Strength and Function in Ambulatory Adults with GNE Myopathy

When I started writing my blog, little over five-and-half years ago, I knew just a handful of GNEM patients. I felt alone, along with my siblings of course, living with such a "funny" disease.  As the years progressed my meeting of patients has grown exponentially. I have met scores of patients and have been reaching out to many on a daily basis around the world. I feel more at ease now, knowing that I have met so many with my disease - we are all in this together.  Meeting you,  contacting you, and responding to your queries, requests, and questions have given me a meaningful purpose to serve our community. Thank you. May our days in 2018 be those of  finding more undiagnosed patients, effective therapies, and cutting developments for GNE Myopathy.





Tuesday, October 31, 2017

Summary of GNE Myopathy International Fifth Webinar on Exercises, Neuromuscular Disease Foundation Newsletter, and GNEM-DMP Newsletter

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GNE Myopathy International (GMI) presented its fifth webinar series on October 14, 2017 entitled Living with GNE Myopathy - Fitness and Exercises. This webinar was presented by Mr. J. Shrader, PT, CPed., and Mr. V. Shieh, BA, a second year medical student, both from the National Institutes of Health (NIH), Bethesda, Maryland.

GMI started these webinar series with the deliberate intention of presenting pertinent and practical information to our GNEM patient community. GMI, along with the WorldWithout GNE Myopathy (WWGM) developed a survey in 2016 that was sent out via email to GNEM patients.

This survey addressed many of the life issues that GNEM patients encounter daily. This survey was intended to collate patient-driven information on therapies and treatments that patients are using or may potentially use.  In this survey most of the patients reported that they found that physiotherapy, supervised exercises, and aqua-therapy were very beneficial to them. This webinar was therefore planned to address GNEM patients' interest and willingness to know more about "Fitness and Exercises."

Imad Kazim, a member of both the GMI team and also a Certified Patient Advocate for the Neuromuscular Disease Foundation (NDF) has known Mr. J. Shrader, PT. CPed., from the NIH for the 7 years. Mr. Kazim introduced Mr. Shrader and Mr.  Shieh to the webinar attendees. He then acknowledged that Mr. Shrader has helped him immensely on how to deal with his ever-changing physical condition.  Mr. Shrader works with the GNEM research team at the NIH.  He is also involved with testing and/or monitoring the strength of GNEM patients. He has been following GNEM patients for more than 8 years. 

This webinar was attended by more than 50 patients from all over of the world (11 plus countries).  Mr. Shrader and Mr. Shieh gave live demonstrations and answered many questions from patients. Both of them cautioned all patients to consult their doctors before starting an exercise regimen.  Here is a narrative of some of the points they covered in their presentations.

1. Why Should We Exercise - We should exercise to improve physical fitness, flexibility, balance, and strength.

2. Muscles and GNE Myopathy - GNEM targets our skeletal muscles including knee flexors and hip adductors.  When we exercise we should try to exercise our quadriceps, gluteus maximus and medius, core, and calf muscles.

3. Exercise Precautions - Avoid overload and overuse of your muscles as these may lead to micro- tears and trauma to the muscle, which in turn will cause irreversible damage to the muscle.  Focus on quality rather than the quantity when exercising.

4. Exercise Considerations - Practical, functional, and assisted exercises with attention to safety.  Aerobic, strengthening, and functional exercises should be included in your plan. Work on the core muscles, and when working out, think about activating groups of muscles rather than an individual muscle. Do not focus only on the weak muscles but on all the muscles.  Focus on maintaining control  over your movements when exercising.  Have professional supervision or an exercise partner when working out.  Maintain proper posture, form, and technique, and allow adequate time for recovery.

5. Monitoring Exercise - Use different tools such as an Apple I watch, a Fit Bit, or the Borg RPE Scale to monitor for intensity and exertion.

6. Finding your Training Zone - Exercise should mirror the way we function in our daily routines.  We should attempt to exercise 2 to 3 times per week.  Training zones are unique for each person as it is relative to the level of physical strength or weakness to each person.  Use 10 repetitions for strength and functional training.

7.  Practical Exercise Modules - These modules consist of very helpful video demonstrations that Mr. Shrader and Mr. Shieh presented.  For more information, please consult the recording.  

8. Question and Answer Session - Questions were asked via a "chat-box",  (anonymously) or directly by individual patients.  Questions ranged from how to use a TENS device and if it is beneficial for GNEM patients; massages, anabolic steroids, types of exercises, what would be the best ankle foot orthoses, and types diet.  Mr. Shrader and Mr. Shieh gave "live streaming" demonstrations to answer some of the questions, to make the appropriate techniques more clearly understood and effectively applied.

This webinar was very practical and useful for patients because we learned applicable strategies that would further assist us to maintain independence for as long as possible, to maintain a high quality of life, we need to find a way to move our limbs no matter how daunting the task.  With the proper supervision and support when exercising we may manage to maintain and or slow down our physical decline. 

To watch this presentation, see the exercise modules, listen to the illuminating question-and-answer session.  Please visit:  
https://vimeo.com/240534737

GMI would like to thank Mr. Shrader and Mr. Shieh from the NIH.  Finally, we would like to express our appreciation, as well to our GNEM community for attending this outstanding webinar.

I am very fortunate to have been working out with an exercise coach for years, and my coach and I have started implementing some of the exercise strategies presented in this webinar.

Links for GNEM Related Newsletters:

1.  NDF Fall Newsletter
2.  October, 2017 GNEM-DMP Newsletter

Monday, October 9, 2017

Webinar on Living with GNE Myopathy: Fitness and Exercises by a Clinical and Research Physical Therapist from the NIH



World Without GNE Myopathy and  GNE Myopathy International will present their fifth webinar series on: Living with GNE Myopathy - Fitness and Exercises.  There have been many unanswered questions on what, how much, and which kinds of exercises are appropriate for us.  Well, here is an important  opportunity to hear from Mr. J. Shrader (NIH) who has seen and tested scores of GNEM patients. There will be demonstrations and ample time for questions and answers.
Here are the details on this webinar




**Addendum:  Mr. Vincent Shieh, BA from the NIH will be co-present with Mr. Shrader for this webinar.





Saturday, September 9, 2017

Press Release from Ultragenyx Regarding Termination of the Sialic Acid (Ace-ER) trial and Some Frequently Asked Questions About the Ace-ER trial

Hope is in our GNE gene!      
Friends, I know many of us are sad with the outcome and termination of the SA-ER study. We must continue on and put our best effort into supporting other therapies, such as the upcoming ManNAc trial (NIH), gene therapy (Dr. Mendell/NDF), and other possible treatments.  Perhaps the prodrug Ultragenyx is working on will prove successful.


Following on from the press release issued by Ultragenyx on August the 22nd regarding the results of the Phase 3 Study (Click for press release)Dr Emil Kakkis M.D., Ph.D., the Chief Executive Officer at Ultragenyx would like to share the following letter with all of the GNEM –DMP registry participants.
 If you have any questions please do get in touch by emailing  hibm@treat-nmd.eu or Nicole.oconnor@ncl.ac.uk and we will try to help. Alternatively, you could consult with your Doctor.
To read the letter from Dr. Kakkis, please click here.  
Finally, thank you for continuing to participate in the registry!
Best wishes,
GNE Myopathy team

Findings of the UX001-CL301Clinical Trial

Dear GNE Myopathy Patient Community,
We announced very disappointing news from our Phase 3 study of UX001 (Ace-ER) which failed to demonstrate efficacy in treatment of GNE myopathy. We did not confirm the benefit in maintaining the arm strength of subjects treated with Ace-ER as we had expected from our Phase 2 study. If there was any effect, it was small and the other endpoints did not provide any supporting evidence for efficacy. Safety was acceptable as previously observed. We can tell that the patients were taking the drug by their serum sialic acid levels. I believe the Ultragenyx clinical team designed and conducted a high-quality study but the treatment effect was unfortunately, not confirmed.
We have been looking at why it did not work and there is no perfect answer. It is clear that the patients included in this study were stronger at baseline but this is what we planned by our inclusion criteria to include people with more muscle to lose, based on our Phase 2 data. These Phase 3 patients did not decline quite as fast as expected but they did still decline in arm strength and Ace-ER had no significant effect. There may be other smaller differences between the studies, but those differences alone cannot fully account for the lack of efficacy in stabilizing the patients. The phase 2 study was small and the Phase 3 study much larger, so it is a better dataset to make conclusions. Without a pathway forward for the product to approval and no positive results, we had to terminate the program and focus on other things at the company.
For patients in our studies or on compassionate use, we are most heartbroken that we cannot offer even a modest therapy for them and that their future now depends on other research work that is ongoing. We will manage this transition graciously to avoid a precipitous stop. We know this is a shocking moment for patients on our studies and for those who feel the drug is helping them. For patients not already on Ace-ER, we cannot initiate new therapy. Whether on Ace-ER or not, the GNE myopathy patient community needs to not lose faith in research but participate in other clinical studies to help get an effective treatment approved. Patients will likely have to be off Ace-ER to participate in other clinical studies.
While we were unable to get Ace-ER to approval, we did contribute to the field and this is very important in the development of any therapy. GNE myopathy is a more widely known disease now among people other than doctors and patients. It is being diagnosed more often with the diagnosis program we supported. We established and made available new methods and endpoints for measuring muscle strength and GNE myopathy patient function as well as gained acceptance for those endpoints from a regulatory standpoint. FDA and EMA know the disease now and a regulatory pathway now exists. Our
DMP natural history study data are very valuable and as planned, all of our data will be available for others doing research on the disease through our relationship with TREAT-NMD. Finally, we will continue our research work to develop a better replacement therapy in our sialic acid prodrug program. If we can demonstrate it has substantial efficacy in animal models then perhaps we can come back to the clinic at some point in the future. We don’t know when that will be but the work is ongoing. In the meantime, we are hoping to see patients participate in other clinical programs and fight this disease everywhere, every day, and all the time, until a solution is found.
Thank you for all you do.

Emil

Some Frequently asked Questions about the SA-Er (Ace-ER) Trial

1. Why is the Sialic Acid (Ace-ER) trial terminated?
a. The Phase 3 Ace-ER study enrolled 89 adults with GNEM able to walk > 200 meters in
the six minute walk test. Patients were randomized 1:1 to Ace-ER at a dose of 6g/day or
placebo for 48 weeks.
b. The study did not meet the primary endpoint of demonstrating a statistically significant
improvement in Upper Extremity Composite score (+0.74 kg, p=0.5387) for Ace-ER
treated patients (n=45, -2.25 kg) compared to placebo (n=43, -2.99 kg) patients for the
change from baseline to 48 weeks.
c. There were three pre-specified key secondary endpoints, including the lower extremity
muscle strength composite score as measured by hand-held dynamometry (HHD),
physical functioning using the Mobility domain of the GNE Myopathy-functional activity
scale (GNEM-FAS), and a measure of muscle strength in knee extensors. The study did
not meet any of these key secondary endpoints.
d. The Phase 3 study was appropriately designed and indicates that Ace-ER did not
stabilize this stronger patient population. We would have expected that there would be
an effect in this population where more muscle is remaining to treat.
e. The Phase 2 study was much smaller and did not have a placebo for the full duration of
the study. The EMA reviewed the results of this study and determined that it was not
sufficient for conditional approval .
2. Should I stop the SA-ER tablets immediately?
a. Please talk to your doctor. It is completely up to you if you want to stop immediately.
You do not have to, but you can if you want. In the phase 3 study, Ace-ER (aka sialic acid
extended release) did not show any benefit compared to placebo in stabilizing strength in the upper extremity or improving the other endpoints.
3. Will I experience withdrawal symptoms when I stop ingesting SA-ER?
a. No evidence of withdrawal symptoms have been observed.
4. When will my trial doctor (investigator) contact me?
a. In the next few weeks. You can also reach out to your study team to talk to them sooner.
5. What are the resources available to me during the transition period?
a. We recognize that some patients feel that they are receiving benefit; however, the overall data did not show a benefit compared to the placebo. Given these results,Ultragenyx has made the difficult decision to end the Ace-ER Program and all studies evaluating Ace-ER in GNE Myopathy.
b. For patients currently in studies or on compassionate use, your physician may request access through compassionate use to provide a reasonable transition. This mechanism
requires approvals by the following groups: Principal Study Investigator, IRB
(Institutional Review Board) / EC (Ethics Committee), & country Health Authority.
MRCC-UX001-00059
6. Can my local doctor or PCP (using central IRB) request compassionate use on my behalf or does it have to go through the study investigator?
a. The study investigator should be in agreement about the risk/benefit profile of the study drug but then Ultragenyx could work with the patient’s local neurologist for a compassionate use request.
7. I feel hopeless now as SA-ER was a very promising solution for GNEM, who should I contact for additional resources.
a. Your doctor(s)
b. The NDF has support resources available to support you
c. ManNac trial: Kennan Bradley, MPH is the Clinical Research Coordinator at the NIH for
the ManNac trials. Contact info: Office: 301-827-7746, Cell: 240-461-0725, Fax: 301-402-0006. https://www.genome.gov/27567243/
8. Will you publish data and when, on the findings of phase 3 study?
a.Yes, we will be publishing the results of the studies and working with GNEM researchers (NDF and TREAT-NMD) to make data available.
9. Do you have other substrates you are considering as a trial for GNEM?
a. We have a pro-drug program for GNE myopathy that is in the very early stages of preclinical research.
10. What is the pro-drug you mentioned at the NDF Symposium you are working on? And how will a pro-drug work if you do not have a drug for it to help?
a. Prodrug is a chemically modified version of sialic acid that is designed to improve delivery to muscle.
11. When will this be available as a trial?
a. At this point we do not know if and when it may make it to the clinic
12. Will this pro-drug work in concert with ManNAc?
a. We do not know at this time.
13. Who should I contact if I need more information why SA-ER was terminated?
a. Kim Mooney at 408.981.3526 or kmooney@ultragenyx.com
14. Could my biopsies/data collected by you be shared with researchers working on GNEM?
a. We will work with Treat NMD, our partner that shares in ownership of the data in the
GNEM-DMP to ensure the data will be available to help support development of other
therapies by researchers and companies.
15. How do I get my individual study results?
a. We will share information with each study site on which subjects received active
treatments vs placebo.
b. Please ask your investigator/ study site for study data related to your muscle 
measurements and other data.

Tuesday, September 5, 2017

Symposium Summary of the Neuromuscular Disease Foundation

"Success is not final, failure is not fatal, it is the courage to continue that counts".   Winston Churchill

Globally we will cure GNEM
It has never before been attempted to gather researchers and GNE Myopathy (GNEM) patients on such a large scale under one roof to discuss and examine the available research on this rare disease. However, the Neuromuscular Disease Foundation (NDF) has now successfully conducted  and completed this in an exemplary manner.  The focus for the 2-day Symposium was to bring together scientists and patients from around the globe in an effort to explore every angle of a cure  for GNEM. A wealth of information about GNEM was presented, and I can only attempt to summarize a very small part of the entire Symposium here.

The presentations by GNEM scientists were intense, packed  with scientific findings, research, patients stories, exercises, and descriptions of adaptive resources.  For more detailed information and accompanying videos, please visit the NDF Facebook page and web site.  Please refer to the links at the end of this summary for additional information.

Lale' Welsh, CEO of the NDF  commenced the Symposium by welcoming the patients, their caregivers, besides scientists who came from all over the world. Immediately following the introductions, we were off delving into two full days of rigorous scientific data. Patients thereafter were able to have their questions answered face-to-face by the researchers.

Symposium Day 1

1.  Dr. Mansbach, Vice President of clinical development from Ultragenyx, stated that he was very saddened by the lack of success of the Phase 3 Sialic Acid trial, which was the last step before regulatory approval. Unfortunately, they were not able confirm the data they showed in Phase 2 of this study.  Since it is necessary to show the FDA that the placebo control group versus the group on Sialic Acid  demonstrated insignificant benefit, making this the end of the road for the development of this compound. He further stated that it is important to try.  Even though this door may be closing, there are other groups that may be able to build upon what has been learned through this trial.  Dr. Mansbach further explained the details on how they designed the Phase 3 Sialic Acid trial and and how the endpoints were tested.


2.  Dr. Lochmuller from Newcastle, United Kingdom, discussed the online monitoring program for GNEM patients he and his team continue to conduct.  It includes a Disease Monitoring Program (DMP) platform where patients can log into their medical file to answer a battery of questions at regular intervals. There is no treatment associated with this program, although they are learning about the most common GNEM mutations that are characteristic in certain groups.  Dr. Lochmuller further mentioned that if we can understand the "modifier gene" we may be able to design a effective GNEM treatment.


3.  Dr. Nishino from Japan presented information on GNEM that was derived from the Japanese population.  In Japan there are 188 registered GNEM patients.  Common mutations within the Japanese group are V603L and D207V.  This latter mutation is in some cases mild or asymptomatic in patients.  Dr. Nishino theorized that there are other options for treating GNEM, such as bone marrow or liver transplant although these are not very easy, practical or even viable to accomplish.


4.  Dr. Rosenbaum from Israel (who identified the GNE gene) mentioned that the precise mechanism of the pathway of the GNE gene and its "interactors" are not yet fully understood.  Even though GNEM is a mono-genetic disease, she stated that we need to understand if and how it is interacts with other genes. She implied that we need diverse research to bring about more understanding of the GNE gene.  Many proteins interact with the GNE gene, thus making the GNE protein problematic to work with.

5.  Dr. Huizing from the National Institutes of Health (NIH) reported that they have been following:
  • 54 GNEM patients in the Natural History study program for the past 6 years and thought that this study had valuable data in terms of how GNEM progresses, how muscles function in regards to different mutations.
  •  The Sialic Acid synthesis pathway has been well studied.
  •  Dr. Carrillo, from the NIH, and her team have come to understand that chronological age is not equal to "Disease Age." Dr. Carrillo and her team have designed a "Disease Progression Model" to assess the Disease Age of each patient they study. As a patient, I see other patients of the same age, I  notice differences in their strengths and their mobility.  This will be a very helpful and standardized tool to give all of us an idea of  what stage we are in the disease process.
  • It has been suggested that perhaps patients who have both mutations on the kinase domain, ManNAc may be more effective
  • ManNAc is a neutral sugar that is slowly released into the blood stream.  It is easily taken up and sialylated, and thus it could still be present in the blood 48 hours after dosing.
  • The NIH plans on starting a multicenter  Phase 3 ManNAc trial on 50 patients later this year. For this study patients will need to be off of Sialic Acid, ManNAc, or any other pertinent medications. Patients will need to pass a Quantitative Muscle Assessment (QMA).  To participate in this upcoming trial, please monitor this site to see when recruitment will begin. Link to monitor for the upcoming ManNAc trial.
6.  Dr. Hegde from Perkin Elmer, Atlanta Georgia, presented her ongoing research on the analysis of various genes and her observation is that GNEM is under-diagnosed and may as well have other genes that interfere and or interact with the GNE gene.  This is an area that she intends to investigate as she partners with the Jain Foundation to study muscular dystrophy.

7.  Dr. Shin from Pusan Nat'l University, Yangsan Hospital, South Korea, presented a short piece on how the South Korean GNEM patients are getting organized to increase the Korean peoples' awareness of  GNEM. There are approximately 50 known patients in his south Korea. (Note: for several years I have been sending emails to neurologists in Korea, China, and other countries, asking them if they know of any GNEM patients, and if so to have them contact me. Finally, I was able to meet a doctor studying GNEM and a patient from South Korea.  Our next frontier is China!


8.  A Panel  led by Doctors Argov, Huizing Shieh, Rufibach, Mansbach Mozaffar, and Shin.  GNEM patients, family members, and caregivers were able to ask various questions from the panel ranging from stem cell therapy to various clinical trials.

Lale' Welsh, CEO NDF, Commences Dinner Celebrations 
9.  At an extensive eloquent dinner served to all attendees on the first day of the Symposium, there were two guest speakers Dr. Kakkis, CEO, of Ultragenyx, and Dr. Jerry Mendel from the Nationwide Childrens Hospital, Columbus, Ohio.

Dr. Kakkis made a conscious choice to come and address our patient community regarding the termination of the Ace-ER (Sialic Acid) trial.  He did not have to come but made the choice to do so any way as he has always had patient well being at the forefront as a therapy for GNEM was being developed. He notified our group that because the Ace-ER trial failed to meets its primary"end points," and further showed no statistical difference between the placebo group and the group taking Ace-ER: they have no other choice but to terminate that study.  There were 89 patients enrolled in this study. Ultragenyx will  continue to support other efforts to find a solution for GNEM.  Currently, they are working on pro-drug program for GNEM which is a version of Sialic Acid that is now in the early stages of a preclinical trial.  

Dr. Mendell outlined the process for applying to the FDA for the pre-IND and IND approval for gene therapy. He further stated that in order to proceed with the gene  therapy process, the following will need to be done:


  • One must have good clinical data to show the FDA such as "proof of concept" and "proof of principle."  
  • Preclinical data to show the FDA, that there is efficacy in an animal model.
  • FDA will then assist the investigators in preparing a delivery scheme to proceed with the chosen form of gene therapy.
  • Dr. Mendell is using the mouse model from Dr.Nishino and the transgenic mouse from Dr. Rosenbaum.
  • The delivery gene that contains the virus still has to be tested on several hundreds mice and on  non-human primates for toxicology purposes.
  • Dr. Mendell also discussed the various vectors, promoters, and systematic delivery methods.
  • There is possibility of a ten fold gene expression in the GNE gene using an MCK promoter which could allow the gene expression to persist for over one year.
  • To proceed with toxicology tests $300,000 is needed and about $3.5 million would be needed to proceed with GNEM gene therapy trial on humans.
Ms. A. Curran, Certified Patient Advocate, NDF shared her impressive GNEM journey and gave the reason for which she became an advocate.
Ms. Lale' Welsh, CEO, NDF presented 10 certified advocates (from various countries) with awards and pins with the hope that they would return to their respective countries and generate increased awareness of GNEM. 
                               Scientists and doctors enjoying an outdoor lunch at the Symposium.
Symposium Day 2

On Day 2 there were various break out sessions as follow:

1.  Mr. Clements, Monterey Peninsula College, CA, worked with patients, family members, and caregivers on various adaptive exercises.
2.  Dr. Tabibian, NDF Board Member, led the patient group in meditation and nutrition.
3.  Dr. Kubacky, Psy.D met with patients only in a private session to discuss various ways to deal with our disease.
4.  Ms. Gelbard, LSCW and Dr. Rahban, both NDF Board Members led a group consisting of family members and caregivers.
5.  Mr. Loren, NDF Board Member moderated a consortium and data-sharing session with scientists, physicians, industry professionals, and NDF Board Members.
6.  Ms. Curran and  Mrs. Voogel, both NDF Certified Patient Advocates, led a patient-only group where they discussed, shared, and demonstrated various adaptive resources that GNEM patients may find practical and helpful in their activities of daily living.

The NDF 's fourth annual symposium was well attended with approximately 40 GNEM patients, family members, and researchers from more than 15 countries. The NDF has planned for this-one-of- a-kind Symposium for over a year.  There were a variety of complexities to pay attention to in order to assure that all our patients get the appropriate transportation from the airport to the hotel, get accessible rooms, and be able to coordinate with vendors for wheelchairs to name a few of the complexities.

Ms. Curran and Mrs Voogel, NDF Certified Advocates set up a "Whatsapp group" to assist with communication and updates of the Symposium. There was a caregiver liason, Mr. Pizzi who was ready to transport the patients and scientists in a shuttle to the various venues around UCLA campus. 


Seen and experienced from the eyes of a GNEM patient, my takeaway from this Symposium is that I felt that we were united as a GNEM group both, patients and scientists.  We were united in one goal and the goal is a cure for GNE Myopathy. Additionally, I felt that we were very fortunate to have these "Giants" (talented, dedicated scientists) working on our rare disease.  There are more than 7,000 rare diseases and GNEM is getting their attention.  

We have had a minor setback with the termination of the Sialic Acid trial, but setbacks are not failures. It may lead us to a deeper understanding in how the GNE gene works and interacts with our other genes. Let us remind ourselves that we are warriors, everyday warriors.  We face extreme challenges every day  with our physical selves. Our long-term vision must be to find a cure.  We must continue the effort to get patients accurately diagnosed in our communities.  We know we have not yet scratched the surface since, per the NIH calculation, there are approximately 40,000 GNEM patients world wide of which only a small fraction is known to researchers. 
Strength lies in number and our job is to find these patients.  


I want to thank my extended GNEM family (my beloved GNEM friends, Lale', Nancy, Amy and Jon) for giving me the opportunity to experience your presence at this Symposium.  Without the undying love of a mother for her daughter we would not have the NDF.
We are STRONG just after our exercises, nutrition presentation, and sharing many practical tips. 
For detailed discussion of the Symposium, please visit:
1.  NDF Facebook Page

2.  Curehibm.org

 "There's a silly notion that failure's not an option at NASA. Failure is an option here. If things are not failing, you are not innovating enough." Elon Musk