The medical trial with valproic acid for mcardle disease.

Since I mcardle disease diagnosed in 2012 I set about researching online all the information they had. I found many foreign websites, especially in English. He had no cure or treatment, some advice, therapy exercises to keep, personal experiences and little else.

Concerning research I found some, most in the mouse model with McArdle's disease created in the Department of Biomedical Research l¨Hospital Vall d'Hebron in Barcelona and one in sheep. The research team at the Institute for Biomedical Research Hospital Vall d'Hebron conducted preliminary experiments valproic acid administered to the mice getting the breakdown of glycogen in muscle cells and activation of brain isoform of the enzyme glycogen phosphorylase. These promising results that qualified were explained using valproic acid in aconference organized by the  Spanish Association of Patients with Glycogenosis (AEEG).The medical director of the project said referring to treatment in humans with only a small amount of enzyme activity were achieved would be able to wipe excess glycogen, even with sub-therapeutic doses. The fact is given that the targets in the promoter of the human gene are much more abundant than in the mouse, making it easier for very small, more sub-toxic doses, would be able to produce that effect. There was also an earlier preclinical trial in Australia with valproic acid and enteric 7 sheep at doses of 20 to 60mg / kg body weight.Compared to untreated animals had a higher expression of the enzyme in the muscle fibers.The response was dose-dependent and reached a maximum of 2 hours after drug application.Before treatment sheep had no myophosphorylase in their muscle fibers. Upon treatment with valproic acid in 5 of 7 sheep myophosphorylase muscle fibers were found. Improving mobility could be demonstrated. The medical director of the research team at the Institute for Biomedical Research Hospital Vall d'Hebron also advanced that in a year (mid-2015) would Preliminary results of representative gene therapy (PTC 124 ). The PTC 124, also known as Ataluren just been approved as an orphan drug for the disease Ducchene so that future trials in humans to disease Mcardle would move very fast.

I continued searching the web for the  EU Clinical Trials Register  which is where the European Union publishes the start of medical treatment trials in humans and search for volunteer patients. And recently in September 2014 I found the first  medical trial in humans with valproic acid for disease mcardle  to be performed in a Hospital in Denmark, but also performed in UK and USA. If the test goes well may still take several years to reach the market, including the drug is approved and licensed by the state agency of the country. 

The tests with valproic acid in 2014. 

In the brain there is a top similar to glycogen phosphorylase called cerebral muscle glycogen phosphorylase. The cerebral form of the enzyme has been seen in muscle fibers after they have been damaged, which Sigere it might be possible to activate the brain enzyme in muscle torque offset the lack of muscle phosphorylase. It is known that some drugs have the ability to activate certain genes. When I was tested in an animal model with McArdle's disease is desmostró that the drug could could operate the brain enzyme in muscle.

In the trial of the drug in human patients with McArdle's disease given a pill every day . between 300 and 600 mg for a period of six months.

 Participants are evaluated three times during the treatment:

• Stress tests as in watts
• Blood oxygen consumption
• Heart Rate
• Blood test
• Rating of perceived exertion during exercise (RPE)
• Measurement by intravenous cannula glycogen levels, ammonia and lactate during exercise.

After treatment:

• Biopsy to evaluate changes in the number of muscle fibers stained positive glycogen phosphorylase and their total content. 
• Heart rate and distance.
• Ability to produce lactic acid in the muscles during the test run.
• Evalucación of symptoms and frequency and mioglubina muscle cramps.
• CK, valproic acid, complete blood count, liver function and kidney function ammonia.

Valproic acid would not be a cure but if a drug test out well would be an improvement in the quality of life of patients by preventing pain and fatigue caused by exercise.