2014 Feb;22(2):390-6. doi: 10.1038/mt.2013.263. Epub
Morpholino treatment improves muscle function and pathology of pitx1 transgenic mice.
Pandey SN1, Lee YC2, Yokota T3, Chen YW4.
Paired-like homeodomain transcription factor 1 (PITX1) was proposed to be part of the disease mechanisms of facioscapulohumeral muscular dystrophy (FSHD). We generated a tet-repressible muscle-specific Pitx1 transgenic mouse model which develops phenotypes of muscular dystrophy after the PITX1 expression is induced. In this study, we attempted to block the translation of PITX1 protein using morpholinos. Three groups of the transgenic mice received intravenous injections of phosphorodiamidate morpholino oligomers (PMO) (100 mg/kg), octaguanidinium dendrimer-conjugated morpholino (vivo-morpholino) (10 mg/kg), or phosphate-buffered saline (PBS) after the PITX1 expression was induced. Immunoblotting data showed that PITX1 expression in the triceps and quadriceps was significantly reduced 70% and 63% by the vivo-morpholino treatment, respectively. Muscle pathology of the mice treated with the vivo-morpholino was improved by showing 44% fewer angular-shaped atrophic myofibers. Muscle function determined by grip strength was significantly improved by the vivo-morpholino treatment. The study showed that systemic delivery of the vivo-morpholino reduced the PITX1 expression and improved the muscle phenotypes. Aberrant expression of DUX4 from the last unit of the D4Z4 array has been proposed to be the cause of FSHD. The findings of this study suggest that the same principle may be applied to suppress the aberrantly expressed DUX4 in FSHD.
Have you guys ever tried in a group to get on dateline,60 minutes,or a like to tell this story for even more support to what really makes perfect sense for these kids for life.
These people just need to see that a drug that changes natural history in a disease like dmd and prevents strong progression of a slow killing health effects is itself a surrogate endpoint.
and the best at that.........................................................................................
YOU JUST NEVER KNOW WHEN..............................................................................SURELY SAREPTA IS WORTH MUCH MORE THAN TODAY'S PRICE WITHOUT SHOCKING NEWS ANYWAY.
my .2 cents
Sarepta would be the treatment after you get the flu ,novavax would be the one to prevent the flu...2 different animals here...so both
Preclinical therapies that restore survival motor neuron (SMN) protein levels can dramatically extend survival in spinal muscular atrophy (SMA) mouse models. Biomarkers are needed to effectively translate these promising therapies to clinical trials. Our objective was to investigate electrophysiological biomarkers of compound muscle action potential (CMAP), motor unit number estimation (MUNE) and electromyography (EMG) using an SMA mouse model.
Sciatic CMAP, MUNE, and EMG were obtained in SMNΔ7 mice at ages 3-13 days and at 21 days in mice with SMN selectively reduced in motor neurons (ChATCre ). To investigate these measures as biomarkers of treatment response, measurements were obtained in SMNΔ7 mice treated with antisense oligonucleotide (ASO) or gene therapy.
CMAP was significantly reduced in SMNΔ7 mice at days 6-13 (p
This type of drug here is only good for short term dosing,not good for long term like dmd or alike ...
however would work on short term problems like viruses ,ect
believe it or not.......fyi
February 10, 2014 /
Thanks again for the sympathetic ear earlier today. Below is my slightly revised draft for your blog. Feel free to publish it along with the picture of Jacob enjoying his salmon cake. Our best wishes to you and Jett.
Dear Drs. Hamburg, Woodcock, Temple, Unger and Farkas,
We are writing today to tell you about our son Jacob, who is 12 years old and has Duchenne Muscular Dystrophy (DMD). When we received the devastating news several years ago that our firstborn had an incurable, terminal illness, our world fell to pieces. Imagine being told that you will slowly watch your child waste away and die over the next decade or so.
As we entered this chapter of our lives, we became aware of the efforts of hundreds of scientists around world working to stabilize, and eventually cure, DMD. A most promising path to those results is Eteplirsen. While the current formulation of the drug will not help Jacob, FDA Accelerated Approval will move the process to develop a formulation that can help him and hundreds of boys just like him. Without drugs like Eteplirsen, Jacob and the other young boys you have read about will slowly die. We stand at a precipice where an entire generation of DMD boys may for the first time be looking at the possibility of a long and productive life. Their families have hope like never before.
We are blessed by our beautiful son Jacob. He has an infectious, positive spirit that fills the room. Although he falls down and cannot run or walk long distances any more, his mind is sharp and focused on his love of engineering and technology. We think of all the good he could do in the world, as an engineer, a researcher, an inventor. Jacob loves food and dreams of being able to cook and enjoy different cuisines, something that boys with DMD lose their ability to do as their swallowing muscles and arms atrophy. Jacob asks us, “what will happen when I can’t feed myself?” Before we turn away with tea
I am looking for a FDA nod for a ''AA''
no one would be better at making this type of drug than Sarepta ....