Earlier diagnosis may lead to better treatment for Parkinson’s

A brain scan can help diagnosis Parkinson’s disease earlier, which may lead to better treatment. Pawan Singh / The National / March 15, 2015

The toll Parkinson’s disease has on individuals can be devastating. Caused by the degeneration of nerve cells in a central part of the brain, it can make walking difficult or even impossible, and cause sufferers to shake. Often, it leads to depression and dementia. It is incurable.

The effect on the loved ones of those with the condition is hardly less devastating. With sufferers eventually unable to do anything for themselves, they require constant care.

As populations continue to age, it is probable that Parkinson’s will become more common. A recent study published in the journal Neurology predicted that the number of people suffering from Parkinson’s in the world’s most populous countries will double from about 4.4 million in 2005 to about 9 million by 2030.

If treatments in people are to be effective, the condition must be identified earlier.

Its classic symptoms –uncontrollable shaking and difficulty with moving – result from the disease’s destruction of a section of the brain called the substantia nigra.

This area produces a neurotransmitter called dopamine, which plays an important role in regulating chemical pathways that control movement. When dopamine levels fall, as they do in patients with Parkinson’s, co-ordinating movement becomes much more difficult.

But by the time these symptoms appear, it is often too late. Typically up to three quarters of the nerve cells in the substantia nigra will already have been destroyed by this point.

Even when symptoms become apparent, it can still be difficult to distinguish from other conditions such as Alzheimer’s. Even experienced clinicians may only able to accurately identify cases 80 to 85 per cent of the time.

Absolute confirmation only comes from the presence inside nerve cells of Lewy bodies, which are aggregations of a protein called alpha-synuclein. But that can only be done once the patient is dead.

Earlier diagnosis, then, would be a massive help. It would make it possible for doctors to intervene with protective and preventive therapies before the disease progresses, and allow for better management of the condition.

The ideal thing – because it’s easiest and cheapest – would be a blood test. Failing that, the ability to make a diagnosis by imaging would be a good second best. And that is exactly what a group of scientists in Al Ain are working on.

Prof Omar El Agnaf, a medical scientist at UAE University in Al Ain, has developed a molecular tool that could let doctors use brain scans to find out if a patient has Parkinson’s.

For several years, Prof El Agnaf and his team have been creating “smart compounds” – peptides, or small proteins, that accumulate in the brains of patients with Parkinson’s.

To start with, Prof El Agnaf’s group tested an array of peptides from a “library” of stock molecules available to researchers, selecting those that were highly specific at recognising and attaching themselves to molecular structures linked to Parkinson’s, such as those of alpha-synuclein.

So far they have been perfecting their method using mice that have been genetically engineered to develop Parkinson’s. They are given the smart compound, which has a “label” element such as the metal gadolinium attached. The compound, with its attached gadolinium, accumulates in the areas of the brain affected by Parkinson’s, and then the gadolinium shows up as red areas on an MRI brain scan. In mice without the illness, the smart compounds do not stay in the brain – and there are no red areas.

“If there is no pathology, the system will clear out the compound in a very short time, says Prof El Agnaf. “In about three hours, you don’t see it anymore. If it has the condition, it will stay – after eight hours it will still be there.”

Being able easily to see when a patient has Parkinson’s has an obvious benefit in alerting doctors to a condition that needs treating. But the treatments currently available are not great – according to Prof El Agnaf, the currently available therapies as mostly geared towards mitigating the symptoms of Parkinson’s, not stopping or even slowing the disease’s progress.

In large part, that is because diagnosis is usually so late, and so uncertain. Without accurate diagnostic tools or biomarkers for the disease, he said drug companies have often shied away from undertaking the hugely expensive clinical trials needed if new cures are to be developed.

But give doctors a readily available tool for diagnosis, such as that promised by the Al Ain scientists, and suddenly there will be a large pool of diagnosed patients who can benefit from better treatments, for whom the disease is not so far progressed as to make the advantage of stopping it marginal.

And that, Prof El Agnaf hopes, will spur the drug companies to action.

Developing a diagnostic tool is one thing. Actually seeing it reach a stage where it can be used routinely on patients is another. As with the testing of new drug treatments, the lengthy process of completing clinical trials and securing regulatory approval must be undertaken.

But Prof El Agnaf, who has collaborations with scientists in Belgium, Switzerland and the UK, believes his discovery has the potential to reach the market.

He is in discussions with a number of pharmaceutical companies and, if he finds the right partner, he believes in five to seven years from now, the method could be at a stage where it could be used with patients.

That means there is the real prospect that, in future, patients developing Parkinson’s will be diagnosed more quickly, and that medical researchers will have better tools at their disposal as they search for improved ways of treating this most destructive of illnesses.

For Prof El Agnaf, who has been researching the disease for more than 15 years, the sense of satisfaction would be immense.

“It is very exciting from a scientific point of view,” he says. “It is a very good breakthrough for us. We feel definitely we are very close to helping the patient. I have always looked to … translate something from the laboratory bench to the patient’s bed, from the lab to a diagnostic tool.

“I have been myself associated with some patients and seen their suffering. It is devastating. That is what motivates me. We feel now we are in a stage where we can give something back.”