Drug found effective in 'silencing' disease gene

A drug has been found to suppress the gene underlying a rare but fatal disease, according to results from an early-stage clinical trial.

Testing the treatment in healthy volunteers, researchers from US biotech firm Alnylam found that the drug 'silenced' a gene associated with a group of heritable diseases known as transthyretin-mediated amyloidosis (ATTR).

Researchers injected the drug, ALN-TTRsc, under the skin of 40 volunteers. The drug — actually short strings of genetic material in the form of RNA — was found to subdue the gene producing transthyretin (TTR), the protein that is faulty in those with ATTR.

Mutations in the TTR gene lead to production of misshapen proteins. These proteins can build up in tissues, eventually triggering organ failure. By halting the gene's activity using a technique known as RNA interference (RNAi), researchers found that levels of TTR protein in the blood reduced by more than 80 percent.

Within the body, DNA is transcribed into messenger RNA (mRNA) which, in turn, is used to produce proteins. Tiny sections of a type of RNA known as small interfering RNA (siRNA) bind to mRNA, destroying it before it can be translated into a protein, effectively switching off genes.

Accumulations of malformed proteins are known as amyloid deposits. Over time, these deposits can disrupt the normal functioning of organs, causing amyloidosis (3).

Familial amyloidotic cardiomyopathy (FAC) and familial amyloidotic polyneuropathy (FAP) are types of ATTR where malformed proteins accumulate in heart or nerve cells, respectively. FAP affects around 10,000 people worldwide and life expectancy is typically between five and 15 years from the time symptoms appear. FAC affects at least 40,000 people and has an average survival of 2.5 years, according to Alnylam. FAP can only be treated in its early stages by liver transplant or a drug called tafamidis. There are no approved treatments for FAC.

'We look forward to continued advancement of our ALN-TTRsc program, including presentation of data from the Phase I trial at the [Heart Failure Society of America] meeting in September, start of a Phase II study in familial amyloidotic cardiomyopathy patients by the end of this year, and - assuming positive results - start of a pivotal Phase III trial for ALN-TTRsc in 2014', said Dr John Maraganore, chief executive officer of Alnylam.