Incredible drug breakthrough for children with fatal muscle disease

This week, while reading the New Scientist I came across this exciting article.

For many children born with genetic disorders such as spinal muscular atrophy or Huntington’s disease, the prognosis is never too good. With spinal muscular atrophy, children rarely survive past the age of two.

This particular disease is caused by the progressive degeneration of a certain neurone (a nerve cell) in the spinal cord, called the ‘alpha motor neuron’. This motor neuron is responsible for transmitting impulses to voluntary muscles, allowing voluntary movement.

This genetic disorder is caused by a mutation in a certain gene, called SMN1 (an abbreviation for ‘survival of motor neuron’), which makes a protein that is crucial for the survival of motor neurons, called SMN protein. When this protein is present in low levels, the motor neurons cannot function so begin to die. Thus the neuron can no longer transmit impulses, leading to weakness in muscles and eventually you cannot move your muscles at all. The cells of suffers of SMN produce faulty versions of this protein, and a very small amount of healthy protein.

Now there has been an exciting breakthrough in possible treatments.

To explain this, first I will provide a bit of background material. As you may know, the blueprints to make everything in our body is written in our DNA. Within our DNA there are small sections, genes (around 25,000 of these) that holds the instructions for making a specific protein. In our case, this gene is SMN1, and the protein is SMN. Now before the protein can be assembled using many amino acids, the DNA must be copied onto a more easily accessible form, mRNA. This mRNA will then bind to a ribosome, which is like a tiny sewing machine, and a protein will be made.

Now to make this protein SMN, the gene coding for it will be transcribed into mRNA and then translated by a ribosome into a protein, which will occur in the neurons that need the protein: The neurons in the spinal chord.

This new treatment targets these small mRNA molecules. If you can interrupt the process of making these faulty SMN proteins that kill the neurons, then the neurons won’t die and the sufferer will still have control over their muscles.

So what will the treatment do? Well, to start with a molecule of mRNA is made in the cell, shown below in blue. Then a drug is given to the patient which contains a length of artificial DNA that is complementary to the RNA made by the cell, shown in red. This is called an ‘antisense’ drug. This red DNA strand binds tightly to the mRNA in blue, and stops it from reaching a ribosome and prevents a protein from forming, or it alters the shape of the protein produced.

Image result for strand of RNA and antisense

This all sounds fantastic, and it works in labs, but you might ask why this has not been produced sooner? Well now we approach the huge obstacle in the way of these treatments. If you inject small pieces of DNA into the blood, the body will very quickly break it down, so it would never reach the neurons in time. To solve this issue the scientist who developed this drug made the DNA much more robust, by strengthening the DNA backbone, which makes them survive for longer in the body.

However this is not the only barrier to cross. To protect the brain and the nerve cells, there is something called the ‘blood-brain barrier’. This is a membrane (in turquoise on the left) separating the blood from the fluid inside the brain and spinal cord (cerebrospinal fluid). This acts as a wall for any large molecules, like DNA. The scientists who developed this new treatment have found a way to modify the Image result for blood brain barrier diagramantisense molecules so they can cross this blood-brain barrier. This means that the drug can be injected straight into the blood stream, rather than into the cerebrospinal fluid which is a painful and risky procedure.

As a result of this fantastic new drug, children with SMN have been observed sitting and even walking with assistance – something rare with suffers of SMN.

Now that scientists have found a way to bypass the blood-brain barrier, there is the prospect for developing drugs for other debilitating genetic diseases such as Huntington’s disease!

Source: Children with fatal muscle disease walk after drug breakthrough


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