Skipping over the stop codon.

OK, a brief science post.. OK, the gene that is messed up in Rett Syndrome is called the MECP2 gene. A gene is basically a set of instructions to build a protein. The MECP2 gene builds a protein that does something in neurons. So in someone who has Rett Syndrome, the instruction to build this protein is screwed up.

Let’s say the correct instructions are:

1. aaa
2. bbb
3. ccc
4. ddd
5. eee
.
.
.
.
24. xxx
25. yyy
26. zzz

OK, so the body knows that when it sees the step “aaa” it knows to begin building the protein and when it sees “zzz” it knows that it’s done building the protein. The “zzz” instruction is called a “stop codon”.

So what can go wrong with the instructions? In Edda’s case, there is a “deletion” which means one of the letters is missing, so you get instructions like this:

1. aaa
2. bbb
3. ccc
4. ddd
5. eee
6. ffg (the letter “f” is missing, everything shifts over 1)
7. ggh
8. hhi
.
.
.
24. xxy
25. yyz
26. zz

So for Edda, starting a certain point, all the instructions are messed up, every single step is “misspelled”.

Another way that the instructions can be screwed up is called a “nonsense mutation”. These look like this:

1. aaa
2. bbb
3. ccc
4. ddd
5. eee
6. zzz the insertion of a stop codon!
7. ggg
8. hhh
9. iii
.
.
.
.
24. xxx
25. yyy
26. zzz

So in step 6, the body sees “zzz” and stops building the protein. But if you figured out a way to get past the “zzz”, the rest of the protein can still be built because the rest of the instructions remain correct.

So this is what someone has figured out, how to skip over the stop codon! PTC Therapeutics has a drug called PTC124 which enables the body to go past the stop codon and build the rest of the protein. How they figured out to skip this misplaced one and not all the other 100 million correct stop codons in the rest of one’s genetic code is a mystery to me. I think they are publishing in this month’s Nature, but I haven’t seen it.

They are testing these already in patients with cystic fibrosis and Duchenne muscular dystrophy. They estimate that 20% of all genetic diseases are caused by nonsense mutations.

So this development, in addition to the recent news that Rett Syndrome can be reversed, puts a real chance of a cure for Rett Syndrome within the next 2-3 years for at least some folks suffering from Rett Syndrome.

Pretty cool!