A cure on the cards?

German researchers are convinced they can cure Alzheimer's, writes Derek Scally

German researchers are convinced they can cure Alzheimer's, writes Derek Scally

GERMAN RESEARCHERS say they have "very convincing proof" that they are one step closer to finding a cure for Alzheimer's disease.

Scientists working in the eastern city of Halle claim to have developed a new way to prevent the build-up in the brain of damaging proteins associated with Alzheimer's.

"We are convinced that our new findings offer a unique chance to prevent the destruction of nerve cells and to stop or inhibit the build-up of protein deposits," says Dr Hans-Ulrich Demuth of the company Probiodrug.

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It's 102 years since the German neuropathologist Alois Alzheimer identified the causes of the disease that carries his name: two abnormal structures in the brain known as amyloid-plaques and neurofibrillary tangles. Plaques are protein fragments that build up between nerve cells; tangles are twisted fibres of another protein - tau.

A century after that breakthrough, however, there is still no conclusive therapy for the disease that causes brain cells to die, resulting in memory loss and increasing difficulties with orientation and recognition.

An estimated 40,000 people have the disease in Ireland, with more than six million sufferers across Europe.

In their quest for a breakthrough, the German researchers spent the last decade examining harmful protein deposits in the brain and trying to find a way to reduce them - or eliminate them entirely.

They concentrated their attention on the enzyme glutaminyl cyclase (QC), found in higher quantities in the brains of Alzheimer's patients. This enzyme is responsible for the production of the protein that does the most damage.

The proteins occur naturally in the human brain but become dangerous when they form amino acid chains that cannot be broken down and cause blockages in the brain. Shut off production of the enzyme, so the theory goes, and the damaging proteins cannot be produced.

After a decade of research work, the theory went into practice at the University of Leipzig with two groups of mice. The scientists say that examination of the group receiving the enzyme inhibitor with their food showed up to 80 per cent less build-up of Alzheimer-causing proteins in their brains.

The treated mice were the same as the untreated control mice, without any side effects, except for demonstrable improved mental functioning.

The German researchers emphasise that it is an early finding in a long-term research process. Nevertheless, after the successful trials on mice, details of which were published in Nature, the researchers will now begin work on a trial on humans which will be completed "in seven years at the earliest".

"It's sad but I'm already getting e-mails from the relatives of sufferers asking if they can have the drug," says Dr Steffen Roßner of the University of Leipzig. "The pain this disease causes for all concerned is huge, so too, then, the will for a breakthrough."

It comes just weeks after another announcement of a new class of drugs, gamma-secretase modulators (GSM), which have been shown to reduce the levels of long proteins that caused the disease and promote levels of shorter protein elements that protect individuals against the disease.

The news has caused mixed reaction among Alzheimer's specialists in Germany.

"This is a new possibility that should be tested," says Kai Simons, an expert in Alzheimer's at the Max Planck Institute for molecular cell biology and genetics in Dresden.

However, he says the method could be described as a "breakthrough" only when it passes stage III testing, namely lengthy trials on humans.

Dr Lutz Fröhlich of Germany's Central Institute of Mental Health was even more cautious, warning that the approach might miss the main target of Alzheimer research: keeping brain cells alive.

In July, studies at the World Alzheimer Congress showed that reducing protein deposits in the brain is, alone, not enough to prevent damage to the brain's so-called "transport processes", causing memory loss so closely associated with Alzheimer's.

Probiodrug is confident that slowing down one Alzheimer's development will have a knock-on effect on other processes. The researchers say they are ready to take on their next challenge: developing a new enzyme inhibitor suitable for humans. The company is confident it can produce such a drug within a year and immediately begin clinical trials.

"For that we will need to work with people in whom Alzheimer's has been identified at a very early stage," says Roßner.