Are we any closer to a cure for degenerative brain disease?

The study by scientists at the UK’s Medical Research Council raised the prospect that a pill could be used in the future to prevent the destruction of brain cells, part of the cause of degenerative brain disease.

We were extremely excited when we saw the treatment stop the disease in its tracks and protect brain cells Professor Giovanni Mallucci

One of the root causes of degenerative brain diseases such as Alzheimer’s and Parkinson’s is abnormally shaped proteins that stick together.

Enough of these proteins can trigger a reaction whereby the brain’s neurons shuts down production of protein in the brain. This ultimately leads to the death of these brain cells.

‘Extremely excited’

The drug tested by the Medical Research Council, which was injected into sick mice, turns the production of protein back on. The mice had prion diseases, such a Creutzfeldt-Jakob Disease, which are also caused by the abnormally shaped proteins.

Five weeks after treatment one group of mice remained free of symptoms such as memory loss, impaired reflexes and limb dragging. They also lived longer than untreated animals with the same brain disease.

Lead scientist Professor Giovanna Mallucci, from the MRC Toxicology Unit at the University of Leicester, said: “We were extremely excited when we saw the treatment stop the disease in its tracks and protect brain cells, restoring some normal behaviours and preventing memory loss in the mice.”

One of the most significant things we have learnt is just how much more complicated Alzheimer’s is than people imagined. Dr Simon Ridley

However, scientists were keen to stress that a human tests for such treatments are a long way off:

“We’re still a long way from a usable drug for humans – this compound had serious side effects”, Professor Mallucci said.

“But the fact that we have established that this pathway can be manipulated to protect against brain cell loss, first with genetic tools and now with a compound, means that developing drug treatments targeting this pathway for prion and other neurodegenerative diseases is now a real possibility.”

Side effects in the mice included weight loss and increased blood sugar. The experimental drug, known as GSK2606414, is made by pharmaceutical giants GlaxoSmithKline.

Turning point?

Professor Roger Morris, from the Department of Chemistry at King’s College London, said he suspected that the findings would be a “turning point in the search for medicines to control and prevent Alzheimer’s disease.”

However, as Dr James Pickett of the Alzheimer’s Society told Channel 4 News, “we have seen a lot of breakthroughs”. So how close are we really to a cure for brain disease?

Dr Pickett does not believe the findings of the MRC research are a turning point: “it probably doesn’t go quite that far, but it is an important part of the jigsaw”.

He said the findings show another mechanism, by which a pathway between the risk factors that are believed to trigger disease such as Alzheimer’s and the symptoms can be traced. It is this mechanism that can be the target of further research into treating or preventing diseaes suich as Alzheimer’s.

Risk factors include things like obesity, stress and infection. He said the idea that you could stop the pathway from these factors to the destruction of cells is “potentially very exciting”.

Complicated

Indeed, it the understanding of the pathologies and symptoms of Alzheimer’s disease has been a hugely significant part of research into the disease, Dr Simon Ridley of Alzheimer’s Research says.

He told Channel 4 News that such research has led to a much greater understanding of what is going on in the early stages of the disease, and has also shown that the disease can be developing for up to 20 years before symptoms begin to show.

It (Alzheimer’s) is like a cancer that only shows itself in the last stages when the body is riddled with it. Dr James Pickett

However, the causes of degenerative disease in the human brain, with its 100 billion neurons, still largely remain a mystery.

“One of the most significant things we have learnt is just how much more complicated Alzheimer’s is than people imagined,” he said.

“Many people thought we would have solved this a lot more quickly than we have, but we are now appreciating the complexity of what we are dealing with.”

Treatments and cures

He said that realistically he thinks a significant treatment for Alzheimer’s could be developed within 20 years.

“The pivotal moment will be when we have a treatment that stops the pathology, or slows it down. A realistic ‘cure’ is something that slows down or prevents,” he said.

“I would like to say this is achievable in 20 years. The standard response you get from the scientific community is five to 10 years, but when you look at what we said we would have achieved five to 10 years ago, most of it hasn’t happened. 20 years is probably more realistic.”

‘A cancer’

Part of the problem is the fact that the disease appears to be “silent” in the body for up to 20 years, and that is why Dr Pickett thinks one of the most important areas of research is being able to detect the disease at earlier stages.

There is an absolutely huge amount of research going on and the key thing is it is in a number of different areas. Katie Le Blonde

“It (Alzheimer’s) is like a cancer that only shows itself in the last stages when the body is riddled with it,” he said.

“We are funding quite a lot of research looking at people in their forties and fifties,” he continued. “We are looking at what is going on in their brains because that is probably the age when the signs are going to start showing.”

It is the “silence” that makes finding a cure difficult. Once Alzheimer’s is detected it is too late.

Human trials

However, trials are taking place on human subjects, and are yielding positive results, says Katie Le Blonde, research programme manager at Parkinson’s UK.

“There is an absolutely huge amount of research going on and the key thing is it is in a number of different areas,” she said.

She pointed to research in Bristol, funded by Parkinson’s UK, into a protein called GDNF which protect brain cells. Human trials of the protein are currently underway.

The idea of a cure, something that restores the brain to what it was, is much harder. Dr Simon Ridley

She also points to gene therapy – “using genes as drugs”. One such therapy being trialled in the UK is Prosavin. People suffering with Parkinson’s suffer from a loss of dopamine, a chemical produced by brain cells that plays a key role in the body’s chemical messages that co-ordinate body movements.

Prosavin converts cells in the brain into replacement dopamine “factories”, its manufacturer, Oxford BioMedica, says.

Another area is drug repositioning, whereby drugs that are already used to treat different conditions, such as diabetes, are found to have a positive impact on degenerative brain diseases.

However, treatments being researched are largely focused on delaying or slowing the impact of degenerative brain diseases. A cure is a different prospect all together.

As Doctor Ridley said, “the idea of a cure, something that restores the brain to what it was, is much harder.”