A genuine, none-better, good news story.
The defect that causes the neurodegenerative disease Huntington's has been corrected in patients for the first time, the BBC has learned.
An experimental drug, injected into spinal fluid, safely lowered levels of toxic proteins in the brain.
The research team, at University College London, say there is now hope the deadly disease can be stopped
The awfulness of Huntington’s disease is hard to describe. The disease is inherited, but it’s possible to pass along the Huntington’s gene through generations without knowing that you have it. And even those who develop Huntington’s generally do so in their 40s, often after having children … and unknowingly passing on the gene.
When the disease manifests, it hits everything. It has all the horrible features of motor-control diseases like ALS combined with memory loss, cognitive degeneration, and personality change, topped off with insomnia, anxiety, and a host of other physical, mental and psychiatric disorders. From the onset of the first tremble to being bedridden, unable to speak or swallow, is a decade-long trail or horrors. Plus there’s a juvenile form that manifests when people are children. It’s worse.
It’s now possible to take a genetic test that shows whether you will develop the disease, but many people in families where someone has had Huntington’s are—understandably—terrified to even take the test. Both because the idea of what’s coming is so horrible, and because of intense guilt over what they may have passed to their children.
So this potential treatment is a big deal. A huge deal.
Experts say it could be the biggest breakthrough in neurodegenerative diseases for 50 years.
On the trial, 46 patients had the drug injected into the fluid that bathes the brain and spinal cord.
The procedure was carried out at the Leonard Wolfson Experimental Neurology Centre at the National Hospital for Neurology and Neurosurgery in London.
Doctors did not know what would happen. One fear was the injections could have caused fatal meningitis.
But the first in-human trial showed the drug was safe, well tolerated by patients and crucially reduced the levels of huntingtin in the brain.
The Huntington’s gene codes for the production of huntingtin protein. It’s not a protein that’s unique to people with the disease. Everyone has a certain level of huntingtin for normal brain development before birth. A genetic defect that prevents the generation of huntingtin is fatal.
But not only do people with the Huntington’s gene continue to produce the protein throughout their lives, they make a different form that is larger and carrying more copies of the amino acid glutamine. The enzymes that normally cut up huntingtin cut this extended version of the protein at the wrong place, leaving behind fragments of protein that can’t be metabolized. The severity of Huntington’s is often defined by just how many extra glutamines get tacked onto each huntingtin protein. The more glutamine, the sooner and more severe the onset of disease.
One thing that often happens is that a gene passed on from the father can get worse across generations. So a man may have a version of the gene that causes symptoms to appear only very late in life, if at all, and never realize he is carrying the Huntington’s gene. But his children can inherit a more potent form that will affect them at a younger age.
That’s just one of several reasons why “people with the disease just shouldn’t have children” isn’t a reasonable way to limit this, or many other, genetic disorders.
The treatment will now move on to longer, broader trials. And the success of this treatment has a lot of fingers crossed that the good news will continue.
The UCL scientist, who was not involved in the research, says the same approach might be possible in other neurodegenerative diseases that feature the build-up of toxic proteins in the brain.
The protein synuclein is implicated in Parkinson's while amyloid and tau seem to have a role in dementias.