Experimental drug lends hope for Huntington’s disease

New hope for Huntington’s disease may be on the horizon.  A research team from the University College of London is stating an experimental drug, Ionis-HTTRx, injected into spinal fluid could be the biggest breakthrough in this neurodegenerative disease in the past 50 years.

What is Huntington’s disease?

Anyone who either knows of someone with Huntington’s disease (HD) or has it themselves is well aware of how devastating this condition can be.  It is an inherited and always fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain and has no cure.  It tends to strike during a person’s prime between the ages of 30 to 50 where it will worsen over a 10 to 25 year period deteriorating a person’s physical and mental abilities. 

To be at risk for Huntington’s means you have to be born into a family who carries this genetic disorder – it is considered the quintessential family disease since every child of a parent with HD has a 50/50 chance of carrying the faulty gene.  The only way to stop the passing down of this faulty gene is to not have children.

All of us have the gene that causes HD but only those who inherit the expansion of the gene will develop HD possibly passing it down to each of their children.  Every person who inherits the expanded HD gene will eventually develop the disease. 

Currently in the United States, there are approximately 30,000 symptomatic patients with HD and more than 200,000 at-risk of inheriting the disease. 

The symptoms of HD are similar to those having ALS, Parkinson’s and Alzheimer’s – simultaneously. The symptoms can include the following:

·       Personality changes, mood swings & depression

·       Forgetfulness & impaired judgment

·       Unsteady gait & involuntary movements (chorea)

·       Slurred speech, difficulty in swallowing & significant weight loss

Promising results from new study on HD

What causes the problem of HD is an error in a section of DNA called the huntingtin gene.  This gene normally has instructions for making a protein called huntingtin, which is necessary for brain development.  These instructions for building huntingtin are locked inside DNA in cell’s nucleus.  The instructions are carries by a short strand of genetic code, called messenger RNA but a genetic error corrupts the protein turning it into a killer of brain cells. The researchers with this new study found a way to possibly silence the gene. 

To combat this gene, they created a drug that is injected into the spinal fluid that bathes the brain and spinal cord.  This injected drug kills the messenger which then prevents the creation of proteins that are damaged, stopping the development of HD.

To try out their experimental drug, 46 patients were injected with the drug at the Leonard Wolfson Experimental Neurology Centre at the National Hospital for Neurology and Neurosurgery in London.  Each patient received four doses of either the new drug or a placebo.  Injecting the drug into the spinal fluid helps it easily reach the brain.  Patients who received the drug had the dose increased over time.  Before and after each injection, the concentrations of the toxic protein were measured in the patient’s spinal fluid. 

Results from this first in-human trial showed that those receiving Ionis-HTTRx saw a significant decline in levels of mutant huntingtin which causes symptoms of the disease.  The higher the dose, the greater the impact, making this the first time the protein has been lowered in pateints with HD.    Another important factor was that the drug was safe and well-tolerated by the patients. 

Even though there is still more long-term data and studies proving this drug can lower levels of huntingtin, it is significant groundbreaking importance to families of loved ones with HD.  The key will be to move quickly to a larger trial to test whether the drug slows disease progression.  Since the results are encouraging, there are plans to conduct a larger-scale trial in hundreds of patients across multiple centers.