Keeping Pace With Adaptive Exercises

I would like to wish my readers, family, and friends a peaceful holiday season with your loved ones. For this post I thought it would be helpful and informative to post some of the exercises I have been doing over the years. Since childhood, I have always been involved in athletics, yoga, and dancing. After the diagnosis I was told my condition will get worse,and I should not engage in strenuous activities because it would break down my muscles faster. Knowing myself, I know I would have to find exercises that I can do as my abilities decline. Gradually, I transitioned from "Ashtanga" yoga to the swimming pool, and now I have incorporated the swimming pool exercises with weight training, cardio workout and stretching. I have been quite fortunate to find two community colleges that offer these adaptive exercises for people with disabilities. All of these exercises, except for the cardio, I do many repetitions as many as I can do without exhausting my muscles. I feel had it not been for these exercises, I would have declined faster. Photo by R.W.Swan(Alaska)

These two machines I do my cardio workout on. One is an elliptical and the other is called a Nu Step.

This machine is a leg press. I have to strap my legs to help them stay together. I add some weights to do this exercise. It helps to strengthen the gluteal and quadricepts muscles. I also feel that my hamstrings get some workout.

This equipment is called an abdominal press, it helps me to stregthen my core muscles which I think has helped me to maintain mobility over the years.

With this equipment I add some weights and pull it over my head. I also do bending exercises with this one, bending forward as if to pick something off the floor.

This equipment is a "lateral pull" I also add weights and pull down. I feel a good stretch around my shoulder blades.

I use this walker to assist me in navigating the exercise room.

Rare Disease Connect Globally

http://www.rareconnect.org/en

Ultragenyx Presented The Findings of Phase 1 Sialic Acid Extended Release (SA-ER) Trial in Australia

Ultragenyx, a biopharma company presented their findings on phase 1 Sialic Acid Extended Realease (SA-ER)tablets at 17th. International Congress of the World Muscle Society earlier this month in Perth, Australia. SA-ER is being tested for Hereditary Inclusion Body Myopathy (HIBM). I participated in this clinical trial last year, therefore the findings are quite personal for me. I am currently participating in the phase 2 trial which will be completed late in 2013. Here, I am attempting to provide a narrative/summary of what I understand from their presentation in Perth, Australia. I have posted the links for those interested in charts and technicalities. As a disclosure, please note I am not a doctor, I am patient directly experiencing HIBM. SA-ER were tested on 26 participants with HIBM. Eight were males and eighteen females. The races/ethnicity were 6 Asians, 20 white, (1 Hispanic/Latino 25 Non-Hispanic). No mentioned was made of Persian/Jewish patients. SA-ER was well tolerated at all given doses with minimal side effects. Depending on the dose levels. SA-ER was absorbed and showed steady amount of sialic acid between 8-16 hours after dosing. They tested SA-ER on the patients when they fasted and with food. Sialic Acid seemed to be in higher concentration with the group that took the medicine with their meals. The evening dose was given closer to the night dose because it is stated that at night time there is protein synthesis and muscle repair, therefore the need for Sialic acid is greater. Besides all these explanations, the one statement I am quite encouraged about is "SA-ER should achieve levels of free Sialic Acid that are expected to correct Sialic Acid deficiency and improve sialylation in the muscles of HIBM patients." Please feel free to send me or write your comments. P.S. Ultragenyx is still recruiting patients for phase 2 SA-ER trial in Los Angeles, New York, Missouri and Israel. http://globenewswire.com/Tracker?data=d6QAld4vepVP7jLm-NEJ9Kbhc9rUIVakuLOTfLBZAFBQWdVKFU9oWPygz-Xe6MYU7lR2sMmxIoUktEeY9c1uczF8F3y9N1PAlpg0rBRAAcBCm4Gr3Jebqm5hEQwRnPosqNDEM0K.8gfRAz-dV3zoX4LRDSYvtdfsa90dnfChvbK8uTPDaK0Rjq439Mc8jDUxhxXhAJKWGDA6mn1dWJjfQdcebeW3fMwZ6oeAHOupszvc6Ptu0NFn7AGJbgM%3D http://www.reuters.com/article/2012/10/10/idUS186788+10-Oct-2012+GNW20121010 http://www.wms2012.com/

National Institutes of Health conducting a Webinar today on Rare Diseases

For all who are able to tune in to this webinar today at 2.30 p.m. eastern time. Please refer to the links below for more details. Undiagnosed Diseases Program - Community Input webinar 10/17/12 2:30 pm ET Start Time: 10/17/2012 2:30 PM ET Duration: 90 minutes URL: https://webmeeting.nih.gov/udp-community_input/ Conference Number(s): 1-800-201-2375 Participant Code: 471324 The Office of Rare Diseases Research- NCATS and the National Human Genome Research Institute are hosting a webinar to provide information to the patient community about a new NIH initiative to expand the Undiagnosed Diseases Program (UDP). In addition, significant time will be dedicated to discussing the issues listed below. We will use the information discussed to help in the selection process of clinical sites for the expanded UDP. This webinar is not to solicit new patients nor to answer diagnostic questions. The physical and financial costs of the diagnostic odyssey What are the major barriers to obtaining a diagnosis? Ready access to specialists, including: Inablity to see a specialist necessary to help obtain an accurate diagnosis Number of specialists seen in order to get an accurate diagnosis Issues getting specialists to talk to each other (coordinated care) Travel requirements (restrictions or limitations due to disease), including: Number of times have traveled out of town to be seen by a doctor when trying to get an accurate diagnosis Number of times have traveled out of state to be seen by a doctor when trying to get an accurate diagnosis Distance needed to travel ever prevented seeing a doctor to get an accurate diagnosis Farthest distance have traveled in order to be seen by a doctor when trying to get an accurate diagnosis Ease of Access to Newer Diagnostic tests, including Problems gaining access to newer imaging or genetic sequencing tests necessary to get an accurate diagnosis Insurance reimbursement issues for costs related to getting an accurate diagnosis Amount of time required to get tests approved by insurance companies/3rd party payers. http://rarediseases.info.nih.gov/News.aspx http://rarediseases.info.nih.gov/files/UDP-%20Questions%20for%20patient%20focused%20webinar%20Oct-2012.pdf

Update on the ManNac( DEX-M74) Trial at the National Institutes of Health

NIH launches trial for rare degenerative muscle disease treatment Researchers have launched a clinical trial to evaluate the drug candidate DEX-M74 as a treatment for a rare degenerative muscle disease, hereditary inclusion body myopathy (HIBM). National Institutes of Health scientists from the National Center for Advancing Translational Sciences (NCATS) and the National Human Genome Research Institute (NHGRI) will conduct the clinical trial at the NIH Clinical Center. HIBM, also known as GNE myopathy, has no available therapy. Disease symptoms emerge in adulthood and slowly lead to progressive muscle weakness. Most patients develop symptoms in their early 20s and eventually require a wheelchair as their arm, hand and leg muscles weaken. Mutations in the GNE gene cause HIBM by producing low sialic acid levels in muscle proteins, which scientists think contributes to the symptoms of muscle weakness. Normally, GNE produces an enzyme that produces sialic acid, a sugar important to muscle development and kidney function. “This study marks an important milestone toward developing a treatment for an underserved patient population, and we would not be this far along had it not been for the teamwork and dedication of the researchers working on this collaboration,” said Christopher P. Austin, M.D., the newly appointed NCATS director. In 2007, Marjan Huizing, Ph.D., an associate investigator in NHGRI's Medical Genetics Branch, led a team of scientists in search of an HIBM treatment. They hypothesized that a compound called ManNAc, now called DEX-M74, might improve the low sialic acid levels that cause HIBM. DEX-M74 is a sugar that the body converts to sialic acid. Huizing and colleagues conducted studies that showed the compound was effective in controlling sialic acid levels in a mouse model with a specific GNE mutation. The researchers published their findings in the June 2007 issue of the Journal of Clinical Investigation. Based on these results, they set out to evaluate the effects of DEX-M74 on progressive muscle weakness in HIBM patients. However, the project required additional funding for pre-clinical studies. In 2009, NIH established its Therapeutics for Rare and Neglected Diseases (TRND) program, now part of NCATS, to facilitate the pre-clinical development of new drugs for these ailments. TRND scientists selected the development of DEX-M74 as a treatment for HIBM as one of its initial pilot projects. The collaboration includes TRND researchers, the laboratories of Marjan Huizing, Ph.D., and of William A. Gahl, M.D, Ph.D., principal investigator of NHGRI’s Medical Genetics Branch, and New Zealand Pharmaceuticals Limited (NZP). NZP is manufacturing DEX-M74, which was developed by Drs. Gahl and Huizing and licensed from the NIH by NZP. "TRND infused life into the HIBM project by supporting pre-clinical studies for the investigational new drug application," said Dr. Gahl, who also serves as NHGRI clinical director. "The program provides the missing link in the evolution of drug treatments. It is a resource that has the potential to develop new therapeutics for rare diseases, often with applicability to common disorders." During the HIBM project, the TRND program has supported toxicology studies to evaluate the safety of DEX-M74. Researchers also generated chemistry manufacturing and controls data, which relate to the formulation and manufacturing process of a drug. Based on the availability of these new data, the collaborators completed an IND application that the U.S. Food and Drug Administration recently allowed to go into effect. "The TRND program was designed to provide the expertise and knowledge needed to advance potential treatments like DEX-M74 to human clinical trials," said John McKew, Ph.D., chief of the NCATS Therapeutic Development Branch and director of TRND. "The results of this project demonstrate what a translational program like TRND can accomplish through collaborations that bring experts together from basic research, pre-clinical drug development, and clinical medicine." The HIBM Phase I clinical trial will test a single dose of DEX-M74 in a small group of patients with a focus on drug safety and how well patients tolerate the drug. Nuria Carrillo, M.D., TRND staff physician and principal investigator of the trial, plans to follow up the initial study with a Phase I/II trial in which patients will receive multiple doses of DEX-M74. Researchers will monitor patients for drug tolerance and indications of drug effectiveness. If DEX-M74 is safe in the Phase I/II trial, researchers will plan a Phase II study to determine the clinical effectiveness of the drug in HIBM patients. "The NIH has achieved a significant milestone in the development of a potential treatment for HIBM, and we are excited about this research reaching the clinical trial stage," said NZP Chief Executive Officer Andy Lewis. "The pre-clinical data are very strong, and we are keen to see DEX-M74 progress through the clinical phases. Once we have proven human efficacy we plan to offer DEX-M74 to patients." The HIBM clinical trial is the third TRND project to advance to human clinical trials. The two other clinical trials are evaluating treatments for sickle cell disease and chronic lymphocytic leukemia. Dr. Carrillo also is overseeing a natural history study of HIBM to collect health information from patients to understand how the disease develops. TRND has developed a portfolio of 14 projects, including HIBM, which focus on rare and neglected tropical diseases. For more information about the HIBM Phase I clinical trial, please visit http://clinicaltrials.gov/ct2/show/NCT01634750?term=HIBM&rank=1. Information about the HIBM natural history study is available at http://www.clinicaltrials.gov/ct2/show/NCT01417533?term=TRND&rank=3. To learn more about TRND clinical trials, please go to http://www.ncats.nih.gov/research/rare-diseases/trnd/trnd-crs.html The National Center for Advancing Translational Sciences (NCATS) aims to catalyze the generation of innovative methods and technologies that will enhance the development, testing and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. For more information about NCATS, visit http://www.ncats.nih.gov. http://www.nih.gov/news/health/sep2012/ncats-24.htm

A Small Car Specially Designed for Someone in a Wheel Chair

This adds another aspect for independence for people in wheelchairs. I drive a car that has hand control mechanisms and would love to drive this car. Please refer to the link at the bottom of the page for the photos and complete article.

This Awesome Tiny Car Has A Secret: Its Driver Is In A Wheelchai
Retrofitting existing cars for handicapped drivers and to store wheelchairs is a huge expense. The Kenguru lets people in a wheelchair roll themselves right into the driver’s seat.

All Stacy Zoern wanted was a car she could safely drive on her own. Born with a genetic condition called spinal muscular atrophy, the intellectual property lawyer uses a wheelchair to get around her downtown Austin neighborhood and calls friends when she needs a ride. So when Zoern, 32, read an article in the spring of 2010 about a tiny electric car designed from the ground up to be wheelchair accessible, she called the Hungarian company that made it and tried to buy one. But the company had halted production right after it completed the prototype. “Their bank loan had fallen through,” says Zoern.

A year later Zoern had raised $2.5 million, mostly from private investors, and bought the company so she could bring the snappy one-seater to market. To get inside the Kenguru (pronounced kangaroo), the driver presses a remote control, and the back hatch pops up. A short ramp descends, and the wheelchair user can roll right into the driver’s area. Drivers accelerate and turn using motorcycle-style handlebars. The 1,200-pound vehicle, which looks similar to a SmartCar, travels at a maximum speed of 25 mph and has about a 50-mile range before its lead-acid batteries need recharging. Because it’s registered as a neighborhood electric vehicle, owners don’t need a driver’s license, but can travel in regular car lanes where the speed limit is 45mph or less. Zoern just began production on the $25,000 Kenguru, which is currently sold only through dealers in Europe. She says she expects the cars to be available in the U.S. within the next year.

http://www.fastcoexist.com/1680559/this-awesome-tiny-car-has-a-secret-its-driver-is-in-a-wheelchair#1

The National Institutes of Health is Recruiting for Clinical Trial Phase 1 with ManNac

The National Institutes of Health (NIH) are now recruiting for phase 1 the clinical trial using a substrate called ManNac for HIBM. This would be a good trial for those of us not particicipating in the Sialic Acid trial to consider participating in. I have participated in the NIH - Natural History study for HIBM, this study is still ongoing. I would absolutely recommend the NIH team working with HIBM patients. They are the best in the field for our disorder. I copied the important parts of the study and have also attached the link for those who would like to participate.
Hope continues to strive.
Tara


A Phase 1 Study to Evaluate the Safety and Tolerability of ManNAc in Subjects With Hereditary Inclusion Body Myopathy (HIBM)
This study is not yet open for participant recruitment.
Verified June 2012 by National Institutes of Health Clinical Center (CC)
First Received on July 3, 2012. Last Updated on September 12, 2012 History of Changes
Experimental: ManNAc
Drug: ManNAc
Single dose
Placebo Comparator: Placebo
Drug: ManNAc
Single dose

Detailed Description:

Hereditary inclusion body myopathy (HIBM) is an autosomal recessive, neuromuscular disorder characterized by progressive muscle weakness with onset in early adulthood. The causative gene, GNE, codes for the bifunctional enzyme uridine diphospho (UDP) N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK), which catalyzes the first 2 steps in the biosynthesis of sialic acid. The subsequent paucity of sialic acid production is presumed to cause decreased sialylation of HIBM muscle glycoproteins, resulting in muscle deterioration. In this Phase 1, randomized, placebo-controlled, double-blind, escalating single-dose study, we propose to provide ManNAc (N-acetyl-D-mannosamine monohydrate) orally as a liquid solution to 3 cohorts of 6 subjects (Cohorts A, B, C) at doses of 3,000 mg, 6,000 mg, and 10,000 mg ManNAc, respectively, or up to the maximum tolerated dose (MTD). The objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single dose of orally administered ManNAc to HIBM subjects, to identify the MTD of a single dose of orally administered ManNAc to HIBM subjects, and to explore the effect of a single dose of ManNAc on potential pharmacodynamic (PD) markers of HIBM. All subjects will be randomly assigned in a 2:1 ratio to receive ManNAc (n=4) or placebo (n=2) and the decision to dose-escalate will be the responsibility of the Safety Review Committee (SRC). Safety will be assessed by adverse events (AEs), clinical laboratory tests, vital signs, physical examinations, and electrocardiograms (ECGs). PK will be assessed for both ManNAc and sialic acid. PD will be assessed by some of the following exploratory biomarkers: serum transferrin sialylation status; plasma glycan profiles; and plasma, white cell, platelet, and urine sialylation status (free and bound sialic acid [N-acetylneuraminic acid] (Neu5Ac)] and cytidine 5'-monophosphate [CMP]-Neu5Ac).
Contacts Contacts and Locations Please refer to this study by its ClinicalTrials.gov identifier: NCT01634750 Contacts Contact: Lea B. Latham, R.N. (301) 827-9235 llatham@mail.nih.gov Contact: Nuria Carrillo-Carrasco, M.D. (301) 402-2324 carrilln@mail.nih.gov http://clinicaltrials.gov/ct2/show/NCT01634750?term=hibm&rank=2

I am of Service to Spread the Awareness of HIBM/Rare Diseases

To my viewers from around the world -  I appreciate you viewing my blog and comments whether private or public.  You give me  the courage to continue with experiencing the challenges of physical challenges . Please feel free to communicate with me on how I may be of service.
Thank you.
Tara

Global Genes is Doing a Survey on Patients' Experience with Getting a Rare Disease Diagnosis

This is survey from Global Genes Project seeking patients with rare disease participation.  Here are their instructions and link.
Thank you.
Tara

Patient Survey: We need your help!

Does your doctor get thumbs up or thumbs down?

Was your or your child’s rare disease diagnosis delayed due to lack of knowledge by doctors?
 Please take 10 minutes to tell us about your experiences with getting a rare and genetic disease diagnosis – your feedback on the process with your doctor could help lots of people with rare diseases!

By providing us with your experiences as a patient with a rare disease, you can help us meet our objectives!

Each participant who completes the survey will be entered into a drawing to win a $200 VISA gift card!
 https://www.engagehealth.com/TakeSurvey.aspx?SurveyID=88MJ4mm

Everylife Foundation and Other Organizations that Address Rare Diseases

I was fortunate to be able to attend an event given by Everylife Foundation in beautiful Tiburon, California to celebrate the passing of the Food and Drug Administration Safety and Innovation Act.  This Act that was passed in July, 2012 has many provisions for patients with rare diseases. This is good news for all patients with a rare disease. 
Some  of the provisions include:
*accelerated development of breakthrough  therapies that show early promise
*Faster Access to Specialized Treatments (FAST)
*Transforming the Regulatory Environment to Accelerate Access to Treatments (TREAT act)
*enhanced FDA consultation with rare disease medical experts
I have attached some links of organizations whose objectives are to advocate for rare diseases,  assist in the development of treatments, help patients, and collaborate with regulatory agencies in various capacity for rare disease patients.  Please refer to the links as I find them very helpful.

http://kakkis.org/
The EveryLife Foundation for Rare Diseases is dedicated to accelerating biotech innovation for rare disease treatments through science-driven public policy. We can do more with the science we already have and bring life-saving treatments to millions of people suffering from rare diseases.

http://www.advocacyforpatients.org/

WELCOME to Advocacy for
Patients with Chronic Illness...

Where patients can get free information, advice and advocacy services in areas including but not limited to the following:

•	How to get your own medical records.
•	How to get and keep health insurance.
•	How to get health insurance coverage for particular treatments, drugs, and/or therapies.
	http://mymuscleteam.lotsahelpinghands.com/caregiving/home/ “What can I do to help?” MDA welcomes you to myMuscleTeam®. We are proud to offer this free personal community and care coordination service. http://www.thespeakfoundation.com/pages/ Welcome The Speak Foundation is a non-profit organization dedicated to helping people overcome the challenges of physical disability or a serious health condition, by providing social support, advocacy, and financial assistance both in the United States and internationally (e.g. sponsorship of orphans with disabilities). You can read more about our mission here.
	p.s. I am so surprised with myself for venturing out to this event which was held at night,( I do not usually go out at night). They had really good live music, a great feast of delicious food , many interesting people, and dancing.  I also surprised myself by dancing in my wheel chair.  I continue to amaze myself.  Hope and Mystery.

Camp Craig Allen Fundraiser in Texas

I am posting this so readers in Texas may partake in this upcoming event. Please refer to the link.

WE'RE HAVING CAMP!!!
		Camp Craig Allen successfully held Inaugural Camp Session for Young Adults with Muscular Dystrophy! Our vision has always been one of a wheelchair accessible/barrier-free camp with no age limit. It started with Craig's dream and has been feverishly worked on since Camp Craig Allen formed officially in 2007 as a 501c3 organization. With tireless volunteers, 5 years of fundraising, and an unsteady economy, it was time to move forward and accomplish some of our goals… at least the goal of getting “overlooked” adults to camp. We just couldn’t wait any longer for millions to fall from the sky to build our own facility. It was now, with an opportunity from another… http://www.campcraigallen.org/

A Rudimentary Explanation into Mutations on the GNE Gene; Amino Acids, Proteins, Enzymes, Exons and Introns

Image from

 

(This is a review from one of my previous posts just to have a little background into understanding my new post).

"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...
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."

Hereditary Inclusion Body Myopathy (HIBM) is known by  many other names such as Nonaka Myopathy, Distal Myopathy with Rimmed Vacuoles (DMRV), IBM2, GNE Myopathy and some others.  Researchers have found  over 60 different mutuations in the GNE gene which result in HIBM.  They may continue to find more mutuations as patients get tested. 

There are clusters of mutations within ethnic groups and we know that HIBM is more prevalent within the Persian Jewish community.  There are other  groups found  in Japan, India and the Middle East.  Most of these groups carry different mutations. In my family, researchers found a "novel" (new) mutation that was not previously mentioned in medical journals.

As with any disease and especially with hereditary diseases it is important to get genetic counseling.  I know most of my friends and family with an HIBM diagnosis have  had counseling with geneticists or doctors.  In my case, I have 2 different mutations, one inherited from each of my parent and both of my  mutations occur on the kinase domain of the GNE gene.

 On the GNE gene there are  two protein sections which are known as domains.  One is called the kinase domain and the other is epimerase. Mutations on the GNE gene occur either on the kinase domain and or the epimerase domain. It is reported in medical literature that the kinase domain consists 722 amino acids and the Epimerase has 753 amino acids.

My mutations were explained to me by a doctor this way:
Imagine the GNE gene like a ruler with 12 inches and for each inch there is a line dividing the ruler in 12 parts which are called "exons". In between the exons are introns. The exons are in charge for the coding of the amino acids in the protein. One of my mutations occurs between th 9th and 10th exon and the other occurs on the 12th exon.  ( Consult your GNE sequencing  report and you may see some information similiar to this).

_____________________________________________________________________________
1           2           3            4           5           6           7           8           9           10           11            12

Epimerase domain                                                                Kinase domain
I have not encountered any medical articles where it mentions whether ManNAc or Sialic Acid would be more effective for a kinase or epimerase mutation


Some terminology that are used  when we talk about HIBM

Exons are segments of dna that carry the codes for  proteins.
Amino acids are small parts of a protein  that are linked together to form a  protein.
Protein are complex organic compounds that are made up of simpler compounds that attach to each and are called amino acids
 Enzymes are  proteins - GNE is a Bi-functional enzyme =  It carries out a 2 step process in the making of sialic acid.  Enzymes can speed up chemical reactions in the body, change a protein or slow down a process.

*Note: I have read and compiled the above information from these sites listed below.  I have also used my GNE sequencing information.

http://glycob.oxfordjournals.org/content/20/3/322.full

http://www.ghr.nlm.nih.gov/gene/GNE
http://www.elmhurst.edu/~chm/vchembook/570enzymes.html
http://www.bbc.co.uk/schools/gcsebitesize/science/add_aqa_pre_2011/enzymes/enzymes1.shtml
http://dwb4.unl.edu/Chem/CHEM869P/CHEM869PLinks/www.bact.wisc.edu/microtextbook/metabolism/Enzymes.html


 Image copied from :http://www.nigms.nih.gov/Education/Factsheet_Genes.htm

Out and About at UCLA Campus

                     (Information for patients travelling to UCLA)
UCLA  campus is nestled in  beautiful Westwood area of Los Angeles. The streets are not as busy and chaotic as Los Angeles proper. The campus was founded in 1919 and stretches over 419 acres. There are some beautiful  sites and I like to observe some of the  architecturally quaint and interesting buildings on the campus and nearby. 
                  When I travel to UCLA, I usually stay at the Tiverton House.  It has about 100 rooms for patients and family visiting the Medical Center.  The Tiverton's staff are very hospitable, helpful, and friendly.  They have handicapped accessible rooms, and an accessible shuttle to take patients to the Medical Center. Request  for the shuttle needs to be made 30 minutes prior to  appointment time.  There is a library, a business room with 2 public computers/printer, a very nice sitting room and some outdoor sitting areas.  They offer free newspapers, breakfast and have a kitchen for those wishing to prepare their meals. There is also a refrigerator and shower chair in the accessible rooms.
                 Almost all nearby business are accessible and they are in close vicinity to  Tiverton House.  There are nearby restaurants that offer room delivery and a big grocery store less than half a block from the Tiverton House.    I love the food at "Native Cafe" which is close by and serves   delicious vegan food.  There is a cafe opposite the Medical Center and may be little  challenging for someone with HIBM to walk to. I  use my battery operated wheelchair  to go to my appointments, restaurants,  and tour around the campus.  Somehow it allows me to maintain some semblance of independence.
                  Good luck to you all going to the Medical Center. Please add to this blog if you have additional information that may help others.
Link to the Tiverton House.http://tivertonhouse.ucla.edu/

Ultragenyx Announces Phase 2 Trial of Sialic Acid on Their Site

Ultragenyx has posted on their web site the initiation of  phase 2 trial using sialic acid extended release tablets. This announcement has been on clinicaltrials.gov site for a while now.
Please refer to the link.  All four centers are recruiting patients at this time.

http://www.ultragenyx.com/index.php?ht=action/GetDocumentAction/i/5045

New Zealand Pharmaceuticals collaborating with the National Institutes of Health on the ManNAc trial - Dex-M74

There has been  quite alot of news on research progress this week with HIBM.  I feel absolutely forntunate to  have met Dr. Gahl and the exceptional staff/researchers at NIH and to see the progress with this study.  For those who are/were involved with the Natural History Study of HIBM, well here is good news. As always, I have attached the link at the bottom of this posting.

New Drug Development Partnership

National Human Genome Research Institute (NHGRI) (Bethesda, MD; www.genome.gov) and New Zealand Pharmaceuticals Ltd (NZP) (Palmerston North, New Zealand; www.nzp.co.nz) have partnered on a drug development project. The goal is to reduce or halt the progression of a rare disorder, Hereditary Inclusion Body Myopathy (HIBM) by treating affected patients with a small molecule therapeutic drug. HIBM primarily affects distal muscle tissue, and due to dramatically decreased muscle strength, most HIBM patients must use a wheelchair by the time they are in their 30s. NZP has licensed NHGRI’s patent portfolio related to treating HIBM and other muscle wasting diseases, as well as kidney diseases related to hyposialylation, with a monosaccharide N-Acetyl-D-mannosamine (ManNAc), also known as DEX-M74. DEX-M74 is one of the first molecules to enter development in the Therapeutics for Rare and Neglected Diseases (TRND) program (http://nctt.nih.gov/trnd) at the National Institutes of Health (NIH). NZP and TRND are currently collaborating to complete needed pre-clinical studies for treating HIBM with DEX-M74 - these studies will be the basis of an investigational new drug application (IND) to be submitted to the Food and Drug Administration (FDA). Once the IND goes into effect, a phase I/II clinical trial is scheduled to begin at the NIH Clinical Center. That study will be led by HIBM expert and NHGRI Clinical Director, Dr. William Gahl, M.D., Ph.D.

http://www.nzp.co.nz/index.php/news/7-news/30-new-drug-development-partnership.html

Updated Instructions on how to Follow my Blog

I have finally figure out how my friends, family and others can follow my blog.  Thanks to all who have been following my postings.
Here are the steps:
1.  Go to my blog site and scroll to the bottom of the page
2. You will see "newer posts", "home", "older posts"
3.  Click "older posts" and scroll back to the bottom of the page
4.  You should see an option for  "join" this site, 
5.  A window opens up, and asks you to sign in using your yahoo, google, twitter account.
4. You could choose to follow publicly or privately

 I know some of my friends have had problems on my site,  please email me if you have any problems or suggestions.

I have attached a link from google with the instructions for following blogs
http://support.google.com/blogger/bin/answer.py?hl=en&answer=104226

New Gene Transfer shows Promise for Limb Girdle and other Muscular Dystrophies

When I was misdiagnosed and placed in the Limb Girdle muscular dystrophy category, I was hoping that the gene therapy the researchers were trying  at the time would be successfull.  This article just released shows how far gene therapy has come and I think  there is great hope for people with HIBM.  I have attached the link of the complete article.

"The challenge of treating patients with genetic disorders in which a single mutated gene is simply too large to be replaced using traditional gene therapy techniques may soon be a thing of the past. A Nationwide Children's Hospital study describes a new gene therapy approach capable of delivering full-length versions of large genes and improving skeletal muscle function. The strategy may hold new hope for treating dysferlinopathies and other muscular dystrophies".


http://www.labspaces.net/121546/New_gene_transfer_strategy_shows_promise_for_limb_girdle_and_other_muscular_dystrophies

Clinical Trials for Sialic Acid by Ultragenyx, and ManNAc by the NIH

The  clinical trial for sialic acid phase 2 is currently recruiting at all 3 sites in the United States and one site in Jerusalem, Israel.  I  have attached the link at the bottom of this blog.  Please send me a comment if you are unable to access the link.

In addition, the National Institutes of Health has  just listed  a clinical trial for phase one of ManNAc.  They are not yet recruiting  for this phase.  The Natural History study continues and they are still recruiting patients to participate in the study.   Likewise, I have attached the links.

On a personal note. I am pleased to state that I have been screened and accepted into the clinical trial  for phase 2 of sialic acid.  I   have been going to the UCLA site in Southern California for the study.

Sialic Acid trial phase 2:
http://clinicaltrials.gov/ct2/show/NCT01517880?term=hibm&rank=5

ManNAc announcement for phase 1:
http://clinicaltrials.gov/ct2/show/NCT01634750?term=hibm&rank=1

Natural History Study conducted by the National Institutes of Health
http://clinicaltrials.gov/ct2/show/NCT01417533?term=hibm&rank=3

Phase 1 for ManNAc announcement, not recruiting yet

http://clinicaltrials.gov/ct2/show/NCT01634750?term=hibm&rank=1

Dr. D. Darvish and Dr. B. Darvish Talks About Their Research and Experience with HIBM

This is discussion by two doctors who have HIBM.  They have dedicated their lives and resources to finding a cure for HIBM. It's quite a touching, poignant and heartwarming story. (For those who are unable to access this link, please let me know).

http://www.laweekly.com/2012-07-05/news/HIBM-rare-diseases-bobby-darvish-daniel-darvish/4/

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