Scientists say they have slowed and even reversed some of the devastating and relentless decline caused by motor neuron disease (MND).
The treatment works in only 2% of patients, but has been described as “truly remarkable” and a “true moment of hope” for the entire disease.
A leading expert said it was the first time she saw patients improve, but this is not a cure.
The MND Association said there was “increasing confidence” in the therapy.
MND, also known as amyotrophic lateral sclerosis (ALS), is caused by the death of the nerves that carry messages from the brain to people’s muscles. It affects their ability to move, talk and even breathe.
The disease dramatically shortens people’s lives and most die within two years of diagnosis.
Les Wood, 68, from South Yorkshire, was the first British patient in the international study, published in the New England Journal of Medicine.
MND had forced him, an electrician, and his wife, Val, a nurse, to give up their careers as walking and using his hands became more difficult.
A mutation in a specific part of its genetic code leads to the production of a toxic form of the protein SOD1, which kills motor neurons. These mutations cause about 2% of MND cases, but one in five of those that run in families.
The 108-people trial, funded by pharmaceutical company Biogen, used an innovative type of drug called gene silencing. The drug tofersen effectively attenuates the defective DNA, so that less SOD1 is produced.
Treatment requires monthly lumbar punctures, where a needle is inserted between the bones in the spine to deliver the drug directly into the spinal fluid.
After six months of therapy, those who received the drug had lower levels of SOD1, but were not physically better.
After a year, however, the rate of the disease slowed — and in some patients, symptoms improved.
Les had his first dose in 2016 – and in home videos shot a year later, he said, “I could honestly say, hand on heart, I felt better.
“I actually walked into the house, without sticks, I thought, ‘This drug works.'”
Now he says, “MND is a progressive disease – so although my symptoms have continued to worsen, I wouldn’t be without the drug and the difference I know it has made to my quality of life.”
For Prof Dame Pamela Shaw, the director of the Neuroscience Institute, in Sheffield, and a veteran of more than 25 clinical trials of the disease, this was something incredible.
She told me: “This is the first where participating patients have reported improvement in their motor function – ‘I can walk without my canes. I can climb my garden steps, which I haven’t been able to do in two years. I can do my Christmas cards this year. write, which I couldn’t last year.'”
The results were a “real moment of hope” and the beginning of a “new era” in which we can expect progress in other forms of MND as well.
In the early stages, the researchers say, the drug stops further damage. It cannot lead to the formation of new motor neurons and it can take a year for the remaining ones to recover and form new connections to muscle tissue.
“It may take time for people to heal from the damage that has already been done,” said Dr. Timothy Miller, principal investigator at Washington University.
“The vast majority of people with ALS experience a relentlessly progressive descent, so the stabilization of function is truly remarkable.”
The treatment is aimed directly at the fundamental cause of this type of MND, so it won’t do anything for the 98% of patients without the SOD1 mutation – although it is hoped that the other mutations, in over 30 different genes, are involved. , can be addressed in a similar way.
“The approach used, reducing proteins that are harmful to MND, will likely have broader applications for more common types of MND,” said Prof Chris McDermott from the University of Sheffield.
Tofersen is under consideration for regulatory approval in the US and will be provided free of charge in the UK ahead of a decision on whether the NHS should pay for it.
dr. Brian Dickie, research director for the MND Association, said the treatment had the potential to provide significant benefit for a relatively rare group of people with the disease.
The big question, he added, was whether the drug should be given in the earliest stages of the disease, when it “may be even more effective,” or even to healthy people with the SOD1 mutation to prevent “the onset of disease.” to prevent”.
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