Aurora magazine

A clinical trial is about to start that will test a new technique to cure blindness. The possible treatment is based on CRISPR and aims to correct the genes that cause Leber's congenital amaurosis. For the time being it will be tested on 18 adult and child volunteers.

The disease is linked to anomalies present in about 15-20 different genes, which cause a progressive degeneration of photoreceptors in the retina. At the moment there is no cure, apart from an effective gene therapy only on the form caused by the RPE65 gene.

This makes the trial even more important. Existing gene therapy uses a virus to replace the abnormal RPE65 gene with a correct version. What we are going to test, however, acts on the Cep290 gene that causes the Lca10 form of Leber's congenital amaurosis. In this specific case, the researchers will use the new Crispr-Cas9 techniques.

Researchers will inject light-sensitive cells under the retina. CRISPR should replace the abnormal gene, so as to correct the DNA of the retina permanently. If it does work, the disease could stop or even regress. In this way children and adults would get their sight or what remains of it. It is not the first time that Crispr-Cas9 is used directly on the human body. A large number of therapies are being developed that exploit the technique of genetic editing, especially in oncology. In these cases, doctors modify the cells of the immune system so that they affect cancer cells.

Source: wired.it

Leber's congenital amaurosis is a genetic disease that causes progressive retinal degeneration. Over the years it causes severe low vision, which can even turn into blindness. It usually occurs around the first 6 months of life and is the most frequent cause of hereditary childhood blindness. About 3 children out of every 100,000 new born suffer from it. One of the typical symptoms of the disease is nystagmus, which is the uncontrolled movement of the eyes.

Together with the progressive loss of sight, it is the first distinctive element of Leber's congenital amaurosis. To confirm the diagnosis, the doctor analyzes the electrical activity of the retina and the genetic analysis. The disease is associated with 15-20 altered genes, although in 5-10% of cases it is linked only to RPE65 mutations. For the disease to manifest itself, the child must inherit two altered copies of the gene. Otherwise, the disease does not manifest itself and the child simply remains a healthy carrier. If there have been cases in the family, it is therefore advisable to take precautions with the appropriate genetic tests.

There are several forms of Leber congenital amaurosis, depending on the genes affected by the anomalies. For most forms, there is no cure and no definitive therapeutic protocol. The only exception is the form that affects the RPE65 gene, for which there is a gene therapy available since 2017. The doctor administers a virus that carries a correct version of the genus in the eye. The therapy has proved effective, especially if inoculated in the early stages of the disease.

Source: telethon.it

One of the things that makes Alzheimer's disease difficult to diagnose is the existence of symptomatic and not symptomatic versions. Despite having the same genetic variants and similar neurological conditions, some patients exhibit different levels of cognitive decline.

According to a study by the University of California, the phenomenon could be linked to the interaction of certain proteins. Family Alzheimer's has a strong genetic component, but the most common is sporadic Alzheimer's. Little is known of the latter. Its risk factors include age, gender and family history. However, social and biological factors that stimulate the accumulation of amyloid proteins also appear to contribute. By accumulating, the proteins form plaques that kill neurons and cause the typical symptoms of the disease.

The researchers studied 414 cases of diagnosed Alzheimer's, comparing it to a healthy control group. In doing so they went beyond genetic analysis and also analyzed the sum of mRNA molecules. From what has emerged, the presence or absence of interactions between proteins can modify how genes express themselves and how the disease evolves. Depending on the groups of genes involved, synaptic transmission and cellular metabolism also change. All critical aspects for sporadic Alzheimer's disease.

The discovery could facilitate early diagnosis of the disease, one of the biggest problems at the moment. A better understanding of how genes are linked and how proteins affect them, in fact, could help to develop tests to be used before the symptomatic phase.

Source: ucsd.edu

Thanks to a study by the University of Tokyo, a group of families has finally received a diagnosis. Their diseases are not caused by genetic mutations, but by the repetition of a small segment of DNA. According to the researchers, this problem could be the cause of other diseases now impossible to diagnose with genetic tests. Diseases such as Parkinson's are caused by mutations located in multiple genes.

The same applies to cystic fibrosis, for which over 1,000 mutations have been identified. In this case, however, the mutation is always the same in all four diseases and is repeated in different areas of the genome. This means that the same treatments could be effective for all diseases, even if to a different extent.

The study focused on adult patients with different forms of neurodegenerative disorder. Among the symptoms most often encountered are cognitive disorders, uncontrolled movements, loss of balance, weakness in the legs and arms. All of these are related to the syndrome of weak X, usually caused by the repetition of three letters of the genetic code in the X chromosomes. Yet the patients involved in the study did not suffer from weak X syndrome. What, then? The analyzed patients had normal X chromosomes, although they exhibited these symptoms.

The researchers then searched for repetitions in the other 46 chromosomes. To speed up the process, they combined modern sequencing techniques with software that looked only for the three offending letters.

Source: u-tokyo.ac.jp