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