Year 2018 welcomes the novel family of FDA approved drugs for inherited diseases. These drugs which are backed by a Nobel Prize and 2 decades of research have the ability to cure inherited diseases without actually editing the delicate genome. It is said that they are powerful enough to give a backseat to CRISPR based gene therapy. One such drug is “Patisiran” developed by biopharmaceutical company-Alnylam for treatment of genetic nerve damage. It works on RNA interference (RNAi) technology.
As we all know that DNA along with messenger RNA (mRNA) produces proteins via transcription and translation process. RNAi does the work of shooting down the messenger and erasing the message for protein production. Scientists believe that this will be greater method for treatment of inherited genetic or immune disorders than gene therapy or immunotherapy. Gene therapy involves cutting out the mutated gene region and replacing it with the new gene but this tampering may have certain risks like ethical regulations, unspecific gene region cut and unpredicted changes in gene silently leading to cancer activation. However RNAi ensures that no bad disease is developed and no bad protein is produced by shooting down the compilation of the message by mRNA.
RNAi not just works on inherited diseases but also on non-inherited diseases like stroke too. In Stroke, group of proteins get activated together to kill the brain cells. RNAi can stop such activation thus protecting the brain cells. Sometimes even good proteins can turn bad upon being faced by any pathogenic situation leading to a disease. As RNAi are reversible when compared to gene therapy, RNAi can be used to silence the proteins temporarily in such circumstances and restore them back to their normal functional state after the change in situation.
So the question arises. If function of RNAi is really that great and it was discovered long back in 1998, what’s stopping this RNAi or RNA technology developed drugs to enter the market? It seems that the production in this technology is easy but the real problem lies in targeting and delivering the therapy to the specified tissue in question. RNAi works by addition of small snippets of synthetic nucleotides which homes the RNAi, delivers it to the disease-causing RNA to silence it. The problem that arises is host immune system gets triggered upon the introduction of these nucleotide snippets in the body and the activation can lead to massive inflammation and even death. To avoid the immune system risk these snippets can be coated in nanoparticles but they will just end up in liver or kidney thus making the RNAi treatment difficult to reach brain, heart or lungs.
Patisiran was successful and approved by FDA for treatment of rare disease called hereditary transthyretin-mediated amyloidosis (hATTR) by targeting the liver itself. The drug doesn’t encounter the delivery problem as the drug wrapped in nanoparticles will be delivered to patients through infusion. As Alnylam Company is focused on the discovery, development and commercialization of RNA interference therapeutics for genetically defined diseases, this approval has given a huge leap for the company to go forward with the technology. The company is seen developing other RNAi-based candidate therapies that aim to treat high cholesterol, bleeding disorders, and Parkinson’s disease.