Tuesday, November 22, 2011

Genetic drug can treat disease causing infant death

A recent animal study has revealed that new drugs interfering with our genes can reduce mortality of the leading cause of infant death worldwide: a disease called spinal muscular atrophy. It is caused by a dysfunctional gene, but fortunately, our genome provides a backup. However, it needs to be modified before it can produce a functional protein, that is able to take over the function of the original one. Spinal muscular atrophy affects 1 in 6000 children, who mostly die young because their body is unable to control muscle function. Scientists have also recently discovered key proteins that are involved with another severe muscle disease, called Lou Gehrig's disease, or ALS. In addition, the genetic basis for a more rare, but not less severe, form of muscle disease has recently been uncovered.

The disease is marked by the inability of the central nervous system to send signals to the muscles in our body. Not only does this cause paralysis, it also results in early death because we need muscles to drive our basic bodily functions, such as breathing. There is however also a mild variant that renders patients able to reach adulthood, though they need a lot of medical care, and can never have a normal life. Because the disease is highly prevalent, considering the fact that it is a genetic disease, and the symptoms are severe, developing proper treatment is much needed.

It is caused by a dysfunction in the SMN-1 gene, that codes for a protein that nerve cells in the spinal cord need to send signals to muscles: without it, the muscles receive no input and are unable to do anything. Interestingly, nature made a backup gene, dubbed SMN-2, which is also able to produce the right protein for nerve signalling. However, SMN-2 proteins are shorter, because the genetic structure causes the cellular machinery to cut parts out of the genetic code that is being read off the gene. A cell forms a protein by using certain molecular structures to make a transcript from the required gene, by making a complementary copy. For this, a cell uses RNA as the messenger code, which is closely related to the DNA that forms our genome. In SMN-2, the cell cuts out parts of the RNA molecule that is being transcribed from the gene.

Researchers from the University of Missouri-Columbia have tried to prevent cells from cutting the transcript, by administering RNA molecules to mice. The pieces of RNA target certain factors involved with the cutting process, dubbed splicing. The scientists have shown that their therapy allow mice to produce full length SMN proteins derived from the SMN-2 gene, improving their symptoms and prolonging their life span.

As for Lou Gehrig's disease, scientists from the Rockefeller University discovered that two proteins called P65 and TDP-43 bind together, which leads to the production of factors capable of inducing an inflammatory process that causes harm to neurons. Eventually, this leads to cell death and to loss of muscle function, similar to what is happening in spinal muscular atrophy. However, Lou Gehrig's disease hits patients later on in life, and does not have a clear genetic background. Stephen Hawking, the famous physicist, is a known patient with Lou Gehrig's disease. He has been confined to a wheelchair for decades, and can only speak through a computer.

The two proteins key to Lou Gehrig's disease form targets that scientists can use to develop new drugs. It has already been shown that blocking P65 improves symptoms in mice. Developing a human drug will require many years, however. In the case of spinal muscular atrophy, it is likely that clinical trials in humans will start soon, though the question remains whether the used RNA molecules are directly compatible for use in patients.

1 comment:

  1. As a sign of gratitude for how my husband was saved from the dreaded ALS, i decided to reach out to those still suffering from this.
    My husband was diagnosed of ALS in 2013 and it was really tough and heartbreaking for me because he was my all and the symptoms were terrible, he had difficulty swallowing, all his joints were dead and that made him immobile to mention but a few. we tried various therapies prescribed by our neurologist but none could cure him. I searched for a cure and i saw a testimony by someone who was cured and he left the contact of the doctor who had the cure in 2015. I never imagined ALS has a cure not until i contacted him and he assured me my husband will be fine. I got the herbal medication he recommended and my husband used it and in three months he was fully okay even up till this moment he is so full of life. ALS has a cure and it is a herbal cure contact the doctor for more info on josephalberteo@gmail.com on how to get the medication. Thanks for reading my story.