Could There Eventually be a Cure for Huntington’s Disease?
Huntington’s disease, a neuro-degenerative disorder, affects roughly 5-10 out of every 100,000 people. The disease acts by deteriorating many structures in the brain, beginning with the Caudate Nucleus, which is involved in motor control. By the end of their lives, patients are expected to lose about 30% of their brain mass.
In the last few decades much has been learned about the disease: we now know that it’s genetic, caused by a mutation on the 4th chromosome, and leads the ‘so-called’ huntingtin protein to grow too long and fold in on itself incorrectly. Parents with Huntington’s disease each have a 50% chance of passing it on to their child. Symptoms usually appear between 35 and 45 years of age, and the life expectancy after the first appearance of symptoms is 10-20 years. There currently is no treatment for Huntington’s itself, so patients can only receive a little bit of relief from their symptoms while the disease progresses.
So far, there is no real consensus among scientists about how exactly the disease works, but it’s generally agreed that it all starts with the mutated huntingtin protein. What if that protein was somehow changed or blocked? This idea prompted some experimentation by Holly Kordasiewicz and her colleagues.
The researchers engineered short, chemically modified strands of RNA, which they inserted into the brains of mice via an animal approximation of Huntington’s disease. The modified RNA strands (or ASOs, short for antisense oligonucleotides,) were used to create huntingtin in place of the mutated genetic codes, resulting in a decrease in the amount of mutated protein present in the diseased brains. This change in the balance of healthy and mutant proteins was enough to stop the brain from degenerating further.
But here’s where the experiment takes a surprising turn: When treatment ended, the mutated huntingtin was still suppressed, even as the amount of ASOs declined. This trend continued for an average of 12 weeks, with mutant huntingtin finally returning to pre-treatment levels 4 months after the treatment had stopped.
Not only that, but in some cases the symptoms of the disease, especially the changes in movement, actually improved with the treatment. Even in older mice, with a longer and more severe progression of the disease, motor skills and anxiety levels began to improve 2 months after treatment ended; these improvements lasted another 7 months (which is when the researchers stopped measuring).
As a final round of this experiment, the ASO treatment was tried for Rhesus monkeys, which have more complicated brains that are much more similar to our own. This time, instead of injecting the ASOs directly into the brain, the researchers used a device called an intrathecal catheter. This device is used to deliver medicine into the space inside the spinal column, where cerebrospinal fluid flows into and around the brain.
The researchers found that with 3 weeks of daily treatment, the amount of mutant huntingtin in the primate brains remained at lowered levels for up to 8 weeks after treatment had stopped. They also found that the ASOs had been dispersed to many different regions throughout the brain, suggesting that symptoms could be treated at their sources in many different areas.
If these modified RNA strands can reduce levels of mutated huntingtin and suppress the production of more at a point when the disease has already taken root, what might happen if the treatment is given to much younger patients who haven’t yet seen any symptoms? Could it be possible that suppressing this step of the disease would allow the body to clear itself out, so to speak, and prevent the symptoms from ever showing up in the first place?
The overall implications of this experiment are groundbreaking: There may be a way to lower the production of mutated huntingtin protein, slow the progress of the disease, improve symptoms that have already appeared, and extend patient lifespan. Is this a cure? Not quite, but it seems like we’re closer to finding one than ever before.
The Brain and Huntington’s Disease – HD Roster
Intrathecal Pumps – Northwest Medical Rehabilitation