DNA therapy for Huntington's Disease

A DNA-based drug that can penetrate brain cells to block the production of a toxic protein might be about to revolutionise the treatment of the...
15 December 2017


A DNA-based drug that can penetrate brain cells to block the production of a toxic protein might be about to revolutionise the treatment of the degenerative condition Huntington’s Disease (HD). The success of a small initial trial of the agent, currently called IONIS-HTTRx, has prompted the pharmaceutical company Roche to license the drug and take it forward. 

The new agent is a synthetic DNA sequence selected to be the genetic mirror image of the gene coding for the nerve cell protein huntingtin, which causes Huntington's Disease.

Injected into the spinal fluid, the agent is taken up by brain cells where it seeks out and locks onto the genetic messages that cells produce in order to make huntingtin. This triggers these messengers to be broken down, preventing huntingtin formation.

In a small, Phase I clinical trial, 46 patients in the early stages of Huntington's received monthly injections of the trial drug at different doses over a 4 month period. Doctors measured the levels of the huntingtin proteins that were made before and after the treatment.

There were no adverse effects, but levels of huntingtin fell and, reassuringly, fell in a dose-dependent manner, so the more of the drug that a patient received the greater the drop in their huntingtin production. This strongly argues that the drug, rather than some other effect, is responsible for the change.

The results do not prove that the treatment will prevent Huntington's Disease in patients who receive the treatment. It's also important to bear in mind that the therapy would need to be repeated regularly for patients to continue to benefit. But since huntingtin causes the disease in HD patients, it seems logical that blocking the production of the mutant protein should arrest the disease progression.

Huntingtin appears to be important during embryonic development of the nervous system but, as far as scientists can tell, does not seem to play a critical role in the functioning of the mature brain. So, preventing its production in an adult doesn't appear to cause untoward effects.

The doctors behind the discovery are also excited because, now the concept has been demonstrated for HD, the same approach could also be used in a host of other neurodegenerative diseases including Parkinson's and Alzheimer's Disease where, like HD, brain cells are poisoned by an accumulation of a pathological protein. The ability to turn off the production of certain proteins in the brain, which is what has been achieved with IONIS-HTTRx, may well open to the door to new therapies for controlling these other conditions too...


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