November 23, 2013

Nonsense Mutation Research

10% of the worldwide CF population have a class 1 nonsense mutation. These mutations have a stop codon in the middle of the protein. The stop codon means that the ribosome stops making the protein at this point, so the normal protein is not produced.

Nonsense Mutations

Worldwide nonsense mutation statistics

Ataluren

PTC Therapeutics are currently developing Ataluren for nonsense mutations. It is believed that Ataluren helps ‘read through,’ allowing the ribosome to ignore the stop codon and produce the normal protein. The results have been mixed so far. It is thought that many copies of the protein instructions (RNA) have already been destroyed by a quality control system before Ataluren is able to help with protein production. See these posts for more information about Ataluren.

Nonsense-mediated decay inhibitors

This is a new approach that targets the quality control system, a system where nonsense protein instructions are noticed by the cell and destroyed.

The nonsense-mediated decay inhibitor blocks this quality control system. If this compound is used in conjunction with Ataluren, it is thought that more CFTR will get past the quality control system, allowing Ataluren to help with the production of more protein, with more functional CFTR reaching the surface. A nonsense-mediated decay inhibitor is involved with laboratory research in the UK.

Sources: CF Trust Press Release and Journal Article (image reproduced with permission from Elsevier)

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Category

1. Class 1 Nonsense Mutations, 3. PTC - Ataluren