Although there are treatments to help with the symptoms of Huntington’s disease there has been nothing to slow the progress of this neurological condition. Now, for the first time, science is offering some hope for people who carry the gene.
Dutch biotech company UniQure has had a breakthrough with a clinical trial in the UK and US of a gene therapy that slowed progression of Huntington’s by an average 75%. Meanwhile, groundbreaking work from New Zealand seems set to make it possible to have a transplant to replace any brain cells destroyed by the genetic disease.
At the University of Auckland’s Centre for Brain Research, they have developed a method of reprogramming human cells so they transform into medium spiny striatal neurons, the specific cell damaged by Huntington’s. In rodents, this technique has already been seen to improve the problems with movement that are typical of the disease, such as involuntary jerking and difficulty walking.
Bronwen Connor, head of the university’s pharmacology department, is optimistic cell replacement therapy will lead to improved quality of life for sufferers – estimated to be about one in 10,000 people, although prevalence is thought to be higher among Māori.
“The aim would be to treat patients early on in the disease progression when the symptoms are not too significant,” she says.
Cell replacement therapies have been around for a while, but the earlier versions used aborted human fetal tissue, which comes with ethical issues.
“For both Parkinson’s and Huntington’s, cells have been successfully transplanted and have survived for many years, producing the chemicals they need to produce,” says Connor. “What the field has been looking for since is a really safe, ethical source of donor cell.”
The technique pioneered by her team uses skin cells, most likely from donors in the case of a genetic condition like Huntington’s. Chemically modified RNA is used to introduce two genes and the cells are then put into a special cocktail that is similar to what they would experience in a neural tube.
“Two weeks later, we have precursor striatal cells that want to be specifically those medium spiny neurons. It’s pretty cool.”
Transplanting cells involves drilling a hole in the skull and injecting into the brain. The rat and mouse experiments have shown significant improvement in motor function within weeks. And months down the track the new cells were still healthy.
Connor says this is not a cure and it is likely to be combined with other treatments. Because the mutant Huntington gene would continue to attack brain cells, including the new arrivals, the replacement therapy could be used alongside gene therapy to block the abnormal protein that causes damage.
Connor points out it may also take some time for the new transplanted cells to be affected.
“People born with the mutant Huntington gene usually don’t develop the symptoms until around age 40 or 50, so it’s taken that long for the cell loss to cause symptoms,” she says. “If we go in at an early stage with new healthy cell replacements then potentially they might have 10 to 20 years of healthy function.”
A similar replacement therapy is being developed for Parkinson’s disease, which causes the loss of nerve cells in the brain that produce the neurotransmitter dopamine. There is also work under way to generate oligodendrocytes, the cells that produce the myelin sheath that is damaged in multiple sclerosis.
Replacement therapy has been tried out by other researchers as a treatment for brains damaged by stroke, but Connor says this is trickier as a wider variety of cells is affected. “With Huntington’s and Parkinson’s there is a selective population of cells that are targeted, so we know exactly what we need to make.”
The first human Huntington’s trial might be possible within five years. Thanks to a Health Research Council grant of $1.2 million, Connor is working towards scaling up the treatment for human use and establishing that it is safe.
“We’re not going to prevent or cure these conditions because the brain is too complex.
“But if we can intervene at an early stage when patients are still getting relief from their symptoms from medication that’s going to make a positive difference.”
