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5 September 2016

Hope in the fight against Alzheimer’s? A new drug focuses on prevention of the disease

A newly developed antibody-based therapy offers new insight on an old method in the race to develop an effective drug against Alzheimer’s disease. 

By Hasan Chowdhury

Last week, Gene Wilder – an actor of great comedic wizardry and star of the 1971 rendition of Willy Wonka – died at his home aged 83 following a three year battle with Alzheimer’s disease. Wilder decided not to impart any information to the public about his struggles with the disease during his lifetime; according to his family, the decision came in part as a measure of protection for his fans.

It’s possible, however, that another element contributed to Wilder’s apprehension to openly share his Alzheimer’s complications; little confidence can be taken in medication currently administered to tackle the disease, often resigning sufferers and their loved ones to assume the worst. In its most debilitative of forms, Alzheimer’s can induce severe memory loss and accelerate cognitive decline. The lacklustre state of treatment may explain why Wilder remained silent on his diagnosis.

A number of drugs have been tested in clinical trials to no avail. It has made pharmaceutical research surrounding Alzheimer’s a high-risk endeavour, one which risks seeing years of work and heaps of investment thrown away, particularly as recent evaluations have found that “99.6 per cent of newly developed drugs failed to make it past clinical trials.”

According to the Alzheimer’s Society, one million people are forecast to have dementia in the UK by 2025. Globally, 75.6 million people are expected to suffer from dementia by 2030. Alzheimer’s disease is one of the main causes of dementia – a progressive disease manifesting from damage to the brain by a range of ailments. It is now at risk of becoming an epidemic problem and in the search for effective medication, a sense of urgency grows.

Any hint of a breakthrough in Alzheimer’s research is usually met with both intense curiosity and scrutiny, which is why the latest contender to step up to the clinical trial plate has, once again, reigned in the attention of scientists and patients alike.

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US Biotech company Biogen and Swiss firm Neurimmune teamed together to lead a clinical trial testing a new drug which seeks to target Alzheimer’s disease in its earliest stages.

Reporting their findings in Nature, Biogen and Neurimmune describe an antibody-based drug called aducanumab, designed to target amyloidβ plaques in the brain – a hallmark of Alzheimer’s. It’s believed that an accumulation of amyloid protein in the brain is the main contributing factor to the disease as it targets healthy neurons and kills them. Targeting aggregates of amyloid with aducanumab could reduce the rate of cognitive decline in patients.

By experimenting with a range of doses of the drug, the researchers found that significant amounts of plaque were removed, particularly when patients were administered with higher doses. Some patients on the higher doses were completely cleared of amyloid from their brains merely a year after treatment.

Though the study was small with just 165 patients tested, a glimmer of hope has been found from the results, as previous antibody-based immunotherapy treatments used to clear amyloid plaques have been unsuccessful.

Discussing the results of the study in a press call, Biogen scientist Dr Al Sandrock explained how the success of this new drug is in its ability to help people before symptoms arise. By searching the brain over for amyloid plaques using a PET scan, aducanumab could target build up of the protein. Sandrock said: “One day you can imagine treating patients with no symptoms if they have amyloid plaques on the brain. We do that with cholesterol where people don’t have cardiovascular disease.”

As promising as the results are, it seems that this potential new Alzheimer’s drug won’t make it to the market without its fair share of problems. Previous antibody-based therapies have failed at later stages of development despite looking promising in mouse models and preliminary clinical trials. It’s also important to note that the study was designed only to test the safety of the treatment, and therefore further work will be required to see if aducanumab is directly involved in slowing down cognitive decline.

There are also more pressing issues. The study was far too small to accurately determine whether aducanumab could have wide scale use, and so a waiting game begins as a larger trial involving 2700 patients from 20 different countries takes place. The 165-person trial undertaken by Biogen and Neurimmune also resulted in patients having potentially devastating side-effects; arising in a number of patients was a condition called Aria, which poses a threat to the brain by causing excessive swelling. To get aducanumab through the next stages of clinical trials, side-effects will have to be ironed out.

Despite criticism, it is possible that this new drug is onto something. Very few treatments for Alzheimer’s, if any, have looked at prevention of the disease as opposed to management. Side-effects seemed to clear after three months, positioning aducanumab in a better place than others. By targeting amyloid plaques with the drug decades before signs of memory loss arise, millions could be steered away from future risks of Alzheimer’s disease and dementia.

Speaking to the Financial Times, Dr Roger Nitsche, president of Neurimmune said: “The effect size of this drug on amyloid removal is unprecedented.” If future large-scale clinical trials produce similar results, incentive to invest in preventative medicine for Alzheimer’s will be increased.