New Advances in Gene Therapies for Rare Diseases


Published on September 5th, 2018

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The U.S. Food and Drug Administration (FDA) recently approved Onpattro (patisiran) infusion for the treatment of peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients.

This is the first FDA-approved treatment for patients with polyneuropathy caused by hATTR, a rare, debilitating and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart and other organs. It is also the first FDA approval of a new class of drugs called small interfering ribonucleic acid (siRNA) treatment.

The newly approved therapy, patisiran, is a drug with ten years in the making by the Cambridge-based Alnylam Pharmaceuticals, for genetic nerve damage. But in this case, the nature of the drug is perhaps more significant: patisiran is based on a technology called RNA interference, or RNAi, which allows doctors to silence genes that are not functioning properly.

This new family of drugs is backed by two decades of research and a Nobel Prize, and have the ability to cure inherited diseases without actually needing to edit the delicate genome.

“This approval is part of a broader wave of advances that allow us to treat disease by actually targeting the root cause, enabling us to arrest or reverse a condition, rather than only being able to slow its progression or treat its symptoms,” said FDA commissioner Scott Gottlieb in a press release. “New technologies like RNA inhibitors, that alter the genetic drivers of a disease, have the potential to transform medicine, so we can better confront and even cure debilitating illnesses,” he added.

“We want to congratulate the FDA on the approval for this new class of therapy. We are very excited that several biotech companies are using this gene silencing approach to solve Alpha-1 Antitrypsin Deficiency (Alpha-1), and at least one is already recruiting for clinical trials,” said Jean-Marc Quach, president and CEO of The Alpha-1 Project (TAP).

“In fact, Arrowhead Pharmaceuticals recently announced that it has completed dosing of a Phase 1 clinical study of ARO-AAT, the company’s second-generation subcutaneously administered RNA interference (RNAi) therapeutic being developed as a treatment for Alpha-1,” assured Quach.

Arrowhead intends to submit a late-breaking abstract with initial clinical data on ARO-AAT to the Liver Meeting®, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD), being held in November 2018.

RNAi works by shooting the messenger: seize, silence, or destroy the carrier, then the message gets erased (our genetic material relies on RNA to shuttle its information over to the necessary cellular factories that make proteins). To scientists, this is a particularly attractive way to treat inherited diseases.

A straightforward approach to dealing with bad genes is trying to replace a mutated gene with a healthy copy using gene therapy. This often involves cutting the genetic material and pasting new data into the new blank space. But the cut is not always specific, and there comes the risk: other genes could be changed, healthy ones can be altered or genes that could cause cancer can be activated.

By acting from a distance, RNAi avoids that risk. The mutated gene, and the genome itself, can be left alone. It doesn’t matter what the code is, if it can’t be compiled, then no running program. No RNA, no bad proteins, no disease.

In other words, RNA acts as a messenger within the body’s cells, carrying instructions from DNA for controlling the synthesis of proteins. RNAi interference is a process that occurs naturally within our cells to block how certain genes are expressed.

About the Alpha-1 Project

The Alpha-1 Project (TAP) is a wholly-owned for-profit subsidiary of the Alpha-1 Foundation singularly focused on providing critical funding and advice to speed the commercialization of therapies for the elimination of Chronic Obstructive Pulmonary Disease (COPD) and liver disease caused by Alpha-1 Antitrypsin Deficiency (Alpha-1).

TAP focuses funding into highly promising drug therapies or devices in the translational research or clinical trial stage of development to speed the commercialization of these therapies. It leverages the experience and scientific knowledge of the Alpha-1 Foundation as well as the drug therapy and device commercialization expertise of large pharmaceutical and biotechnology companies.

Learn more in The Alpha-1 Project website.


Sources: FDASingularityHubArrowheadBusinessWire and the Alpha-1 Foundation


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