NORD - site, Affordable Care Act

For those who are unable to access the NORD site, here is what they have to say about the Affordable Health Care Act that the  Supreme court voted on yesterday.

 

National Organization for Rare Disorders, Inc. (NORD)

about an hour ago

NORD fought long and hard for insurance reforms during the two-year debate leading up to the Affordable Care Act. These reforms included elimination of discrimination based on pre-existing conditions, ending annual & lifetime insurance caps, and more. While the Affordable Care Act isn't perfect, it included these reforms, and we will continue to monitor to make sure these reforms are implemented.

FDA User Fee Bill Promises Real Hope for Rare Disease Patients

 Please refer to the link attached, it is  from the Rare Disease Legislative Advocates website.
 I am very encouraged by this section...

The Creating Hope Act, sponsored by Kids v Cancer, creates additional incentives for industry to develop treatments for rare pediatric diseases and cancers by granting a voucher for priority review status that the sponsor can use to expedite review of another product. ULTRA/FAST, spearheaded by the EveryLife Foundation for Rare Diseases seeks to improve access to the accelerated approval process for rare disease treatments, significantly decreasing the time and cost of FDA review while maintaining high safety and efficacy standards.

http://www.congressplus.com/events/index.cfm?action=Event_Page&eventcode=QKN6SF&bypass=true

Update on the Sialic Acid Trial in Japan

I know some of us were asking about what happened with the sialic acid trial in Japan.  Here is what I found.  I have attached the link at the bottom of the page.  Also please note it states Pub-Med in process.

 Brain Nerve. 2012 Mar;64(3):255-61. [Sialic Acid supplementation therapy for distal myopathy with rimmed vacuoles]. [Article in Japanese] Nishino I, Noguchi S. Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Distal myopathy with rimmed vacuoles (DMRV), also called hereditary inclusion body myopathy, is an autosomal recessive disease that typically affects tibialis anterior and hamstring muscles in young adults although other muscles are also involved in later stages. The disease is caused mostly by missense mutations in the GNE gene that encodes a protein with two enzymatic activities in sialic acid biosynthetic pathway: UDP-GlcNAc 2-epimerase and ManNAc kinase, respectively catalyzing the rate-limiting step and the subsequent reaction. Accordingly, sialic acid production is reduced in patients' cells and cells are hyposialylated. We have previously shown that this hyposialylation status can be recovered by simply giving sialic acid, suggesting that hyposilylation status in the muscle should be the cause of myopathy. In support of this notion, myopathic manifestations were virtually completely suppressed by oral administration of sialic acid in our DMRV model mice. Similar efficacy was seen also by ManNAc, precursor of sialic acid, or sialyllactose, a conjugate form of sialic acid. Based upon these in vitro and in vivo results, phase I clinical trial for sialic acid supplementation therapy for human patients was conducted in Japan in 2011. Another phase I trial, using slow release tablets of sialic acid, is currently in progress in the US. Hopefully, phase II trial to see the efficacy of the therapy will be initiated soon. PMID: 22402719 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/22402719

Article from Boston Globe - New Drug Research

This is a good article from the Boston globe and also posted on the Rare Disease Legislative Advocates site.  It discusses the collaboration amongst Biopharmas, patients, and other regulatory agencies.  It is very encouraging for patients of rare diseases.
http://www.bostonglobe.com/business/2012/06/19/patients-driving-direction-new-drug-research/TjWu74aFVH2g4wNPhUbfQL/story.html?s_campaign=8315

Guarding my Independence With "Fierceness" and Accepting Help when Needed

 As  I acquire direct experience  living with HIBM,  I am learning that I must not give in easily and let others do my tasks.   I know that when I have stopped doing an activity/tasks/chores, out of fear for one reason or the other I have  gotten weak faster. 

With this insight into my disease progression, I know I must keep doing chores and other activities with safety in mind.  When I  do accept help from of family, friends, and strangers  I know I have done all I can and, therefore would not be able to do the task. Additionally, I know when I accept help  that I am not defeated; it is just that I need  help at that time. Also, I know I must pay attention to the doing as there is a delicate balance between overexhausting the muscles (which could cause faster deterioriation) and using them in a way to maintain increased longevity. 

I find that HIBM is devastating to my body.  At times, it is predictable in its progression, and other times very unpredictable.  Usually, I am able to feel and notice the gradual weakening of a certain muscle and at times certain muscle abilities are taken away overnight.

 I have experienced this phenomena  many times during the course of this disease.  For example, I have two steps in the back of my home that I have climbed up and down  for the past ten years to go  into my beautiful back yard.  One day however, I climbed down the steps into my backyard, checked out a few of my rose bushes, and dediced to come back in.

When I attempted to climb up the steps I found my legs/feet would not lift, and my knees refused to bend.  At that point,  I  thought about the strategies I could use to get back into my home.  I sat on the top  step and picked up my feet with my hands, one at a time  placed them on the lower step, and tried to stand up that didn't work, I tried pulling myself by holding onto notches and ledges which also didn't work.  I made several attempts using other methods however, to no avail.

After about 30 minutes of trying all the tricks I have acquired over the years I decided to ask for help. I was helped up the steps by someone holding one of my hands and giving me a gentle pull, and I swung one leg/feet to clear the first step and then repeat the motion to get back into my home. After that a grab bar was mounted next to the steps to assist me.

I feel quite sad that I have lost the ability to climb steps without someone's help and know that I have no control over this.  Proactively, when I exercise, I continue  to practice climbing steps within  parallel bars with hopes of reviving my stair climbing ability.  I am very fortunate to have an extraordinary and intuitive coach who helps me with this.

Although, it feels like I  go through a daily "battle" with my body by coaching and coaxing my limbs to cooperate,  I am thankful that I can do some things.   My intention is  to continue walking,  no matter how  strange my gait may look. I  strive fervently to remain independent eventhough it may take me an hour to do something which previously I was  able to do in 15 minutes. 

HIBM is a disease that manifests itself at the prime of one's life and ekes away at one's independence, productivity, physical abilities and tests one's self confidence. There is hope and I am very encouraged with the progress of the clinical trials and other research that are being done.

HIBM Cause and Potential Treatments

GNE's official name is "glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase." The Gne gene is called a "bi-functional" enzyme which gives instructions to make an enzyme in the body. This enzyme sends messages between cells and tissues to carry out certain functions.

Included in one of this enzyme functions, after it has gone through some chemical changes is to make sialic acid. Sialic acid is a simple sugar which is needed by  the muscles to function normally. In HIBM, a kind of dysfunction/defect happens in the pathway whereby adequate amount of sialic acid is not available for the muslces and cells.

At a point in this production cycle we get a substance (substrate) called ManNAc which is changed to to ManNAc-6 (this means a phosphate molecule is added), later along this cycle it then changes to sialic acid.  Because there is less sialic acid available for the muscles they get weaker and we get HIBM.

Some potential treatments for HIBM which have been published and are being  experimented by scientists and researchers are Sialic acid and ManNAc.  It is believed that some of these may stop the progression of the muscle breakdown and restore some functionality to the muscles. (It is still a debate as to whether all the muscles will regain  the strength). 

Some other forms of treatments are being explored such as gene based therapy which is still in it's "early" stage of development  and may have the answer for a cure for HIBM. In addition, Intravenous Immuno Globulin or IVIG has been tried with a small sample of HIBM patients.  http://hibm.org/arm/_media/about_arm:2010-04.pdf  http://clinicaltrials.gov/ct2/show/NCT00195637?term=hibm&rank=5

Currently, there are two entities working on the "substrate" part of  clinical trials.  Ultragenyx a biopharma company is working on Sialic Acid Extended Release in a tablet form.  They have finished  phase one and  is starting phase 2 trial at three different sites in the U.S.A. and one site in Israel.   http://clinicaltrials.gov/ct2/show/NCT01517880?term=hibm&rank=4

The National Institutes of Health in Bethedsa is doing a "Natural History" study where they are gathering information to measure and understand the progression with HIBM.  Most likely, they may start a trial with ManNAc later this year.   http://clinicaltrials.gov/ct2/show/NCT01417533?term=HIBM&rank=2

Personal Note:
As a person who has HIBM, I have become increasingly aware of how extensive research has to delve into a disease in order to come up with experimental "mouse"models to test a particular medicine on.  This process takes years, dedication on the part of the researchers, and enormous amount of money for a treatment/medicine to get to the market.  Hence, it is such a  precious gift to me  that Ultragenyx, NIH, and HRG/ARM have put so much work into studying HIBM and attempting to speed up treatment(s) for HIBM.

References:
http://wiki.medpedia.com/Glucosamine_(UDP-N-acetyl)-2-epimerase/N-acetylmannosamine_kinase_(GNE)
http://ghr.nlm.nih.gov/gene/GNE
http://www.jci.org/articles/view/30954/files/pdf
http://clinicaltrials.gov/ct2/show/NCT00195637?term=hibm&rank=5
http://www.bdipharma.com/Clinical-What-is-IVIG.aspx

http://alsn.mda.org/news/neuralstem-seeks-expand-stem-cell-trial

Allowing and accepting your suffering

                                             
  After my children’s father, my beloved husband passed away unexpectedly, and later learning that I would become a “disabled person”; I had to dig deep to find the strength to continue living. I have contemplated how I would end my life and hence end my suffering however, where would that have left my 2 year and six year old kids. At that crossroads, which became one of my defining moments I decided to live life with passion. This passion brought me back to a girl of 12 year old where I danced on my parents’ coffee farm in South America. Through dancing on the ‘parapets’ on this farm I have experienced (the 4 M’s) magic, miracle, mystery and the mystical. The 4 M’s as I call them have continued to grace my life, more so as I become more disabled I have incorporated ‘Shantideva’s wisdom into my everyday practice. Shantideva says ”If there is a way to overcome suffering, then there is no need to worry, if there is no way to overcome suffering then there is no no use in worrying”.
                                          It takes some practice in reading this quote.

My Story Into Understanding LGMD--->Gene--->GNE---HIBM--->

In trying to understand what ails me and some in my family medically and physically, I have embarked on a quest to bring understanding and insight into a disease called Hereditary Inclusion Body Myopathy or HIBM for short. I will learn all I can, explore, and bring awareness of this disease to anyone who will listen.

Years ago after my eldest sister started walking “funny” (a waddling kind of gait) we did not know what was happening. We thought because she just had her first child it may have to do with that. As time progressed however, another sister started walking “funny”. They lived in South America where, at that time, it was difficult to get an official diagnosis. They were told they have a form of muscular dystrophy(Limb Girdle Muscular Dystrophy or LGMD). Later, I had myself checked out by a neurologist and the tests proved inconclusive. About twenty years later I joined their waddling gait club.

This was a very scary and confusing time for me. I went through many scenarios of doom and gloom, and what if’s. At the end of this dark tunnel, I decided that I must take action. The actions I have taken then was to study articles, research findings, and seek out anyone who knows anything about my disease. I have consulted numerous doctors, scientists, and laypersons from near and far about Limb Girdle Muscular Dystrophy. I spent most of my time trying to get a definitive diagnosis. One research hospital had my biopsy taken and sent parts of the biopsy to various institutions and, as new tests became available they would put a fiber from my muscle to see if it would be positive for a subtype of LGMD. Still my muscle fiber failed their tests for LGMD with no definitive diagnosis.

Then a little less than two years ago, I got phone call from one of the team members of the Children’s Hospital in Boston. She said “I have news for you”. Long sigh on my side with my thoughts spinning on many levels. “your family does not have LGMD but something called Nonaka Myopathy”. At that instance, I was thinking that no one in my family is Japanese and myopathy relates to muscle. She was able to explain to me what Nonaka Myopathy is and it is called by different names i.e. HIBM, Distal Myopathy with Rimmed Vacuoles-DMRV, GNE Myopathy.

I felt an enormous relief, a kind of freedom like a heavy weight have been lifted. Towards the end of my conversation with her I stated “ I feel fortunate to have HIBM”. In many aspects I do feel fortunate. The most immediate, was my family and I have finally gotten a definitive diagnosis. I was also asked to contact HIBM/HRG lab founded by a compassionate doctor Dr. D. Darvish.

Next Gene, GNE, HIBM

Our Genes and how we get a Mutation -- GNE Gene

A little look into our human genes. In a human body there is one genome, 46 chromosomes, and between 75 to 100 trillion cells. In the human genome there are over 25,000 genes (according to some estimates and the number fluctuates).

Each of us have a slight variation in our genomes which makes us unique. In most instances, these variations do not cause a problem in our bodies. When they do however, we have what is known as a genetic mutation.

Genetic mutations can cause diseases which affect our bodies basic building blocks - proteins. Proteins have many functions such as strengthening our bones, grow hair and muscles, and regulate other functions in the body.

Hereditary Inclusion Body Myopathy (HIBM) is a rare disease and many rare diseases are caused by mutations in a single gene. With HIBM, we have variations or mutations occuring on the GNE gene.

I find it such a great wonder that researchers were able to locate and isolate this one gene (GNE) out of the thousands in our body which causes HIBM.
A note: I am a lay person trying to bring an understanding and awareness to HIBM.

References: http://www.genome.gov/Pages/Education/AllAbouttheHumanGenomeProject/GuidetoYourGenome07.pdf