Most people I have spoken with since Ella was diagnosed with SMA have told me that they had never heard of this disease.
Neither had we.
Yet it remains one the most devastating genetic diseases out there.
How does Spinal Muscular Atrophy happen anyway?
The answer lies in the genes. A single protein.
Here, it looks a little something like this...
The SMN1(Survival of Motor Neuron) gene is what people with Spinal Muscular Atrophy are missing. This gene produces the protein that keeps our motor neurons alive.
The SMN1 (Survival of Motor Neuron) gene is located on chromosome #5.
Mother nature produces two of these genes on chromosome #5:
*an original (SMN1): This is missing in people with SMA
*and copies (SMN2): People with SMA can have up to 6 copies
The two models below show how SMN1 and SMN2 genes make their proteins and how Spinal Muscular Atrophy occurs:
Normal SMN1 protein production
(model below)
proceeds as follows:
- (a) The DNA is "spliced" by the RNA
- (b) The RNA then translates the spliced parts making a protein using 8 full portions (called exons)
- (c) The mRNA transcribes the entire protein (using all 8 exons)
- (d) A normal (functional) SMN1 protein is produced.
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Since people affected by SMA do not have the [original] SMN1 gene they are reliant upon the [copy] SMN2 gene to produce the needed protein.
Spinal Muscular Atrophy occurs (on the SMN2 gene) because:
(see model below)
- (a) The DNA is "spliced" by the RNA
- (b) The RNA then translates the spliced parts BUT the #7 portion (exon) is deleted or mutated, making an insufficient protein.
- (c) The mRNA transcribes the protein without the #7 portion (exon) or with a mutated form of it.
- (d) An "Unfunctional" SMN2 protein is produced: SMA Results
In short: People with SMA do not have the original SMN1 gene (therefore they do not produce the protein needed for their motor neurons to survive).
They do, however, have back-up copies of the original gene called SMN2 (some people produce more than others: Our Ella has three copies.)
The problem with the back-up copy however is that it is missing or has a mutated key component (exon #7).
If you look at the RNA (b) part of the picture above you will see that while the SMN2 gene is "splicing" it skips or mutates the #7 portion (exon) of the gene. This skipping/mutation produces an "unfunctional" SMN2 protein...Spinal Muscular Atrophy is the result.
The SMN2 protein is not sufficient to keep the motor neurons alive for very long and they slowly die off; hence the progressive, degenerative aspect of SMA.
Researchers' Approach:
A pharmaceutical company is set to begin phase 1 clinical trials using SMNRx.
Clinical trials occur in 4 phases:
- Phase 1: Researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
- Phase 2: The experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
- Phase 3: The experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.
- Phase 4: Post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
Courtesy of: http://clinicaltrials.gov/ct2/info/understand
