Stop the Nonsense

Messenger RNA is used by the body to encode proteins based on the structure of certain genes. In mRNA as in DNA, genetic information is encoded in the sequence of four nucleotides arranged into codons of three bases each. Each codon encodes for a specific amino acid, except the stop codons that terminate protein synthesis.

But what happens if the DNA of the genes mutates, or becomes corrupted? Sometimes it causes the wrong proteins to be encoded. Sometimes, the DNA mutates in such a way that the Messenger RNA is prematurely truncated.

Example (thanks to Wikipedia):

    DNA: ATG ACT CAC CGA GCG CGA AGC TGA
   mRNA: AUG ACU CAC CGA GCG CGA AGC UGA
Protein: Met Thr His Arg Ala Arg Ser Stop

Now, suppose that a mutation occurs in the DNA:

    DNA: ATG ACT CAC TGA GCG CGA AGC TGA
   mRNA: AUG ACU CAC UGA GCG CGA AGC UGA

The RNA derives from the DNA (where UGA derives from TGA) In this case, UGA is a stop codon, so the protein produced by this interaction looks like this:

Protein: Met Thr His Stop

"Okay," you're saying, "but why go into all this detail?"

The answer is fairly simple. The type of mutation described above is called a "nonsense mutation." It has been estimated that n most genetic conditions, between 5-15 per cent of cases are caused by these types of mutations.

But a new drug by PTC Therapeutics, now in Phase II clinical trials, allows the cellular machinery to read through premature stop codons in mRNA, and thereby enables the translation process to produce full-length, functional proteins.

The drug, known as PTC124, has already had encouraging results in patients with Duchenne muscular dystrophy (the most severe form of muscular dystrophy) and cystic fibrosis. The drug has excited scientists because research suggests it should also work against more than 1,800 other genetic illnesses, including spinal muscular atrophy, hemophilia, lysosomal storage disorders, retinitis pigmentosa, familial hypercholesterolemia and some forms of cancer.

PTC124 won't be a cure-all for these types of conditions, but if it can be effective in 5-15% of cases, this could be one of the most promising new drugs of the decade.