In August of 2021, Intellia Therapeutics of Cambridge and its partner Regeneron Pharmaceuticals published a study reported in the Boston Globe, showing results of a single treatment using CRISPR-Cas9 technology. This revolutionary treatment reduces the effect of a misfolded protein produced in the liver of people with transthyretin amyloidosis (ATTR). Worldwide, the disease affects about fifty thousand people.
About Transthyretin (ATTR) Amyloidosis
Familial (inherited) amyloidosis is the result of the transthyretin protein changing its shape and forming fibrous clumps. The misshapen proteins accumulate in damaged organs resulting in abnormal function. The heart and nerves are especially affected.
The protein can be reduced by several approved treatments if taken regularly. The goal of Intellia’s clinical trial is to develop CRISPR treatment that can permanently reduce transthyretin in just one treatment.
At the start of its clinical trial last August, Intellia was the first biotech that successfully infused CRISPR therapy directly into the bloodstream. When the CRISPR therapy reaches the liver, the gene that causes the toxic protein is deactivated.
About the Study
Cas9 is often called molecular scissors because they break the transthyretin gene, thus reducing buildup and production of the disease-causing protein.
Scientists have indicated that their goal is to remove more transthyretin protein from tissues than the amount that has been stored. In this way, it may halt the progression of the disorder and may also help patients to eventually improve.
During the clinical trial last August, transthyretin levels were cut by Intellia’s lowest dose only two weeks after infusion. Then a medium dose caused an 87 percent drop of transthyretin in the blood. The toxic protein was cut by 93 percent after infusion of Intellia’s largest dose.
The trial has now been expanded from six to fifteen participants. Four doses of Intelllia’s therapy have now been tested.
This week, new data was released indicating that not only was treatment durable, but the highest dose brought improved results over last year’s lower levels.
Looking Forward
A follow-up of trial participants will determine whether disease-related organ damage can be reversed. However, the encouraging results bring Intellia closer to its goal of creating a gene-editing treatment for patients with genetic diseases.
