Aurora magazine

On July 28, 2017, Charlie Gard, the British kid with mitochondrial DNA depletion syndrome died. It is a rare genetic disease that causes the progressive decline of DNA in mitochondria. Since mitochondria are the organelles that give energy to the cells, the muscles lose weight slowly and lead to death.
There is a chromosome in the DNA that produces only 13 proteins. Despite being few, each of these is necessary for the proper functioning of mitochondria. Inside the mitochondria there are then about 1,000 protein chains encoded by genes of nuclear DNA.

In decomposing mitochondrial DNA, some nuclear genes work badly. Malfunction leads to DNA leakage from mitochondria. Mitochondria therefore lose the ability to produce energy and the organs that are affected are the ones that consume more. Muscles, liver and brain, left uncharged, stop functioning.
The symptoms of mitochondrial diseases are very heterogeneous, but the most common are muscle weakness and difficulty in feeding. Various forms of the disease have in common the early manifestation, which takes place in the early days or months of life. In these cases the symptoms worsen rapidly. Progression, on the other hand, is slower in later forms.

Mutations that cause mitochondrial DNA depletion are recessive. For the disease to manifest, it is necessary to inherit the mutated gene from both parents. The diagnosis takes place with a targeted examination, which serves to quantify mitochondrial DNA. To this is added the genetic test, which allows to identify the mutation.

To date there is no cure and only treatments exist to mitigate the symptoms.

Source: repubblica.it

A study by the Gemelli Clinic and the University of Glasgow identified the molecule that determines the appearance of rheumatoid arthritis. Discovery could lead to the creation of new therapeutic solutions.

Subjects with arthritis exhibit an excess of miR34a molecule. It is a non-coding RNA molecule that does not encode for a protein but for other RNA molecules. The molecule produces pro-inflammatory molecules, pushing the immune system to attack healthy tissue. The most violent attacks are against the connective tissue of the joints, which swells and causes pain.

In 50-60% of cases, rheumatoid arthritis is caused by genetic factors. The remaining 40-50%, however, depends on different factors. Some of these are smoke and excess weight, which often act on genetically predisposed subjects. In some cases epigenetic factors are referred to, ie environmental factors that determine DNA responses.

Drugs on the market are effective only in some cases. They tend to be generalized or too specific. Some act on a single cell population, although the disease may affect at least 4 or 5 populations. The only way to effectively fight the disease is to opt for personalized therapy. Time factor also plays an essential role: the first thing you do is the better the results.

The researchers developed a murine model to study the role of the miR34a molecule. In specimens in which the molecule producing gene has been eliminated, arthritis has disappeared. That means miR34a is a breaker for the disease: hitting the molecule also means striking the disease. The next step will be to elaborate therapies that affect miR34a.

Source: repubblica.it

Researchers at the National Institutes of Health (NIH) have demonstrated the efficacy of an experimental drug against Niemann-Pick type C1. The compound activates the AMPK enzyme and activates the cell cleansing mechanisms. This reduces cholesterol and fat accumulation in the brain and liver.
Work could lead to a new generation of Niemann-Pick type C1, Parkinson and Alzheimer treatments. All of these neurodegenerative diseases have in common the malfunction of cellular recycling mechanisms. Neurons accumulate bad substances that affect their functions.

The experimental drug 2-hydroxypropyl-β-cyclodextrin is in Phase 3 of the clinical trial for the treatment of the disease. Preclinical studies had already shown its effectiveness, but operation was unclear. The researchers then created a more powerful version, methyl-β-cyclodextrin.

The team tested methyl-β-cyclodextrin on cells taken from patients with Niemann-Pick. The drug has been linked to the AMPK enzyme and has activated it. The result was a collapse of accumulated cholesterol levels. By blocking AMPK's activity, however, levels have remained unchanged. Researchers also found other effective compounds that could lead to new drugs.

The tests have clarified how methyl-β-cyclodextrin acts. The next step will be to check whether 2-hydroxypropyl-β-cyclodextrin works in a similar way.

Source: nih.gov

A team of international genetics has identified the fundamental mechanism behind congenital myotonic dystrophy. Grace to the discovery, researchers have developed animal models of the disease, which will serve to study new possible treatments.

Thanks to the study, researchers realized that poor regulation of some gene expression leads to developing the disease. The ultimate goal is to identify new techniques for prenatal diagnosis, both early treatment and minimizing symptoms. In fact, the disease causes extreme muscular weakness, respiratory problems and intellectual deficits. Finding it right after childbirth would help children grow in an almost normal way.

The researchers found that the main cause of the disease is a malfunction of the RNA. Injecting some RNA molecules alter abnormalities in the expression of essential genes for muscle development. One of these anomalies causes the breakdown of a particular key protein during prenatal development, resulting in subsequent muscle problems.

By including the operation of the disease, it has been possible to develop more precise animal models. In this way, researchers began a new phase of research, which should lead to more accurate diagnosis and treatment tools.

Source: ufl.edu