A landmark trial for Huntington’s disease has announced positive results, suggesting that an experimental drug could become the first to slow the progression of the devastating genetic illness.
The results have been hailed as “enormously significant” because it is the first time any drug has been shown to suppress the effects of the Huntington’s mutation that causes irreversible damage to the brain. Current treatments only help with symptoms, rather than slowing the disease’s progression.
Prof Sarah Tabrizi, director of University College London's Huntington's Disease Centre who led the phase 1 trial, said the results were "beyond what I'd ever hoped ... The results of this trial are of ground-breaking importance for Huntington's disease patients and families," she said.
The results have also caused ripples of excitement across the scientific world because the drug, which is a synthetic strand of DNA, could potentially be adapted to target other incurable brain disorders such as Alzheimer's and Parkinson's. The Swiss pharmaceutical giant Roche has paid a $45m licence fee to take the drug forward to clinical use.
There are an estimated 500 people in Ireland with the disease and one Irish family said the breakthrough was a potential lifeline for those living with the condition.
Ann from Co Kildare, whose husband is in the end stage of the disease, on Tuesday welcomed the results.
"I cannot put into words how momentous it is. I can say to my children we've gone this long hard road, with no hope, but now for the first time ever there is hope," she told RTÉ's Morning Ireland.
She said her husband has been sick for 26 years. “The entire family is worn out. The children grew up as carers, they don’t have any memory at all of ‘normal dad’ they’ve only known ‘sick dad’.”
“They’ve only known taking responsibility, being his carer, instead of him being their carer. It was complete role reversal.”
Two of Ann’s three children have been tested, one of them has tested positive for the disease and one negative. The third child has not been tested.
It’s hereditary
“My daughter who tested positive has watched the long, long progression of this illness. She has helped care for her dad all her life, so she knows what’s coming for her. That’s the cruelty of the disease, it’s hereditary.
“This news of a breakthrough for family members, it is so exciting. It gives us the first real, tangible hope since the gene was discovered in 1993.
“I have prayed every day for a breakthrough - living with this illness, you cannot put into words how devastating it is to suffer, how devastating it is for a family, especially children who know that this can be store in them.”
In the study an experimental drug was injected into spinal fluid which was found to safely lower the levels of the toxic proteins that cause the disease.
Dr Edward Wilde, principal researcher at University College London said: "So far we haven't shown reduction in the symptoms - the trial that we ran was a very short trial of 46 patients worldwide who took part - they only received four days of a dose of the drug over a four month interval, that's a very short period in a very long illness.
“We wouldn’t have expected to see any change in rates of progression and certainly don’t see any signs of stopping the disease.
“What we have seen is a really strong, really encouraging piece of chemical evidence that the drug is doing what it’s supposed to do, which is lowering the level of the toxic protein in the spinal fluid where it was injected.
“It’s a drug that does some pretty fundamental things to the human brain, to patients whose brains are already not working completely efficiently. The drug is made from DNA and is injected into the spinal fluid - it enters brain cells and alters the switching on and off of the Huntington gene which causes the conditions. In doing so, it tells the cells to make less of the toxic protein.
Degenerative disease
“Spinal injections are unusual in a degenerative disease - the safety results from the trial were very encouraging. There were no signs of concern related to the drug or the procedure. It really is a big thumbs up to take this drug to the next stage.
“The 46 who participated in the trial will be invited to take part in an open label extension study - over the coming months they will be invited to start receiving the drug in a research setting, they will all get the active drug, rather than a placebo.
“The next big step is a longer trial to see if it can slow the progression of Huntington’s disease, can it delay the worsening of symptoms. That trial is now being planned. It is likely it will involve hundreds of patients for a much longer period of time. That’s the trial we hope will get the drug licensed.
“In theory, this drug, if it works, will work for everyone that has the Huntington’s disease mutation. Everyone who has HD and everyone who is destined to develop Huntington’s has the same basic mutation in the same gene, this drug targets the product of that gene and so theoretically it should work to slow or even reverse symptoms in people who already have it.
“If we give the same drug early to people who have the mutation, but don’t yet have the symptoms, theoretically, it should delay or even prevent the onset of symptoms.
“We can now envisage a future where this drug is given early in life to people who have a positive genetic test. It can be used to change the course of their life - hopefully prevent the disease.” - Additional reporting Guardian