A cure for Parkinson’s disease could be on the horizon after scientists stopped symptoms in mice.
The revolutionary gene therapy destroys a toxic protein found in the brains of patients, a study found.
It offers hope of the first drug that treats the cause of the devastating neurodegenerative illness and might even have applications in some forms of dementia.
The poisonous chemical, called alpha synuclein, also clumps together in the grey matter of some dementia sufferers.
Senior author Professor Hideki Mochizuki, a neurologist at Osaka University, Japan, said: “We expect in the future, this method will be used to not only successfully treat Parkinson’s, but also dementia caused by α-synuclein accumulation.”
Parkinson’s affects 128,000 people in the UK. As well as damaging movement it affects the senses, memory and mood.
Blocking the accumulation of α-synuclein in the brain prevented its development in the lab rodents. This was done with a simple injection into their spinal canal.
Lead author Dr Takuya Uehara, a member of Prof Mochizuki’s lab, explained: “Although there are drugs that treat the symptoms associated with PD, there is no fundamental treatment to control the onset and progression of the disease.
“Therefore, we looked at ways to prevent the expression of α-synuclein and effectively eliminate the physiological cause of Parkinson’s.”
One in ten cases of Parkinson’s are hereditary. The vast majority are sporadic, meaning they occur at random with no family link. The a-synuclein molecule plays a major part in both forms.
The researchers say the findings published in Scientific Report provide “a ray of hope” for the millions of patients worldwide.
Although more common in the over 60s it can strike at any age, with 10 to 20 percent of patients diagnosed before they reach 50 and about half of those under 40.
And while not fatal in and of itself, the progressive degeneration often causes secondary effects that lead to death.
The exact cause is still a mystery, but it is believed both genetics and the environment are involved.
All patients show a loss of neurons in the brain that produce dopamine, a chemical that controls movement, and increased levels of α-synuclein.
These accumulate in Lewy bodies, molecules that develop inside nerve cells and are a pathological feature of both familial and sporadic Parkinson’s – as well as some types of dementia.
Dementia with Lewy bodies is the third most common cause of dementia, affecting about 100,000 people in the UK.
People with the disease experience distressing symptoms such as hallucinations, problems with movement similar to Parkinson’s and ‘cognitive fluctuations’ – variations in alertness, attention and thinking skills.
So the team designed short fragments of DNA that are mirror images of sections of the α-synuclein gene.
These were were stabilised using a chemistry technique called ‘amido-bridging’ that connects atoms.
The resulting pieces, called ASOs (amido-bridged nucleic acid-modified antisense oligonucleotides), bind to matching bits of DNA known as micro RNA (mRNA).
This prevented it from being turned into α-synuclein. After screening 50 different ASOs, the researchers settled on one that slashed the protein levels by 81 percent.
Co lead author Dr Chi-Jing Choong said: “When we tested the ASO in a mouse model of Parkinson’s disease, we found it was delivered to the brain without the need for chemical carriers.
“Further testing showed the ASO effectively decreased α-synuclein production in the mice and significantly reduced the severity of disease symptoms within 27 days of administration.”
The mice had been genetically engineered to develop a rodent form of Parkinson’s.
After the therapy they performed better in a series of tests devised to measure their motor function and control – such as walking on beams and wires and gnawing at pasta.
In Parkinson’s, toxic proteins build up in the brain to kill nerves, particularly those linked with movement.
It affects one million people in the US – and up to 10 milllion worldwide – causing muscle stiffness, slow movement, tremors, sleep disturbance, chronic fatigue, an impaired quality of life and severe disability.
Celebrity sufferers include Michael J Fox, Billy Connolly and Sweet Caroline singer Neil Diamond. It claimed the life of boxer Muhammad Ali.
Added Prof Mochizuki: “Our results showed gene therapy using α-synuclein-targeting ASOs is a promising strategy for the control and prevention of Parkinson’s disease.”
