Alzheimer’s disease is the most common form of dementia, loss of mental function, responsible for at least 60 percent of cases. There’s no cure and currently no effective treatment – all that can be done is to try to deal with the symptoms.
In the brain of a person with Alzheimer’s disease, there are lower levels of a chemical called acetylcholine. Acetylcholine helps to send messages between certain nerve cells. In Alzheimer’s disease some of the nerve cells that use acetylcholine are also lost. Because of these changes in the brain, symptoms of Alzheimer’s disease get worse over time.
Donepezil, rivastigmine and galantamine all prevent an enzyme called acetylcholinesterase from breaking down acetylcholine. This means there is a higher concentration of acetylcholine in the brain, which leads to better communication between nerve cells. This may ease some symptoms of Alzheimer’s disease for a while.
In 2019, according to the Alzheimer’s Society there were over 850,000 people with dementia in the UK, representing one in every 14 of the population aged 65 years and over. By 2040, there will be over 1.5 million people with dementia in the UK, at the current rate of prevalence.
But now there’s some hope for more effective treatment, though not a cure, with the approval in the US of the first new treatment for Alzheimer’s in 20 years.
The disease takes its name from Alois Alzheimer (1864-1915), who first described the pathology of the disease. The first sign is short term memory loss. This develops to further symptoms including more severe memory problems, confusion, disorientation, personality changes and problems with language and speech.
Alzheimer’s Disease affects the brain physically. Amyloid-b protein deposits known as plaques build up in an abnormal way in the brains, forming tangles which damage connections between brain cells. The brain actually becomes smaller than normal, and as the disease progresses, the symptoms become worse. But because it develops slowly, it can often be difficult to recognise, but memory loss and confusion leads to eventual death.
After many years of disappointing studies of potential treatments for people living with Alzheimer’s disease, the U.S. Food and Drug Administration recently approved a new drug called Aducanumab, which holds out some promise for treatment, though not a cure. The drug is controversial, though, because it didn’t follow the usual regulatory path, and some advisory panels are still not convinced that it works.
Biogen Inc., a Cambridge, Massachusetts-based biotech company, and Japanese pharmaceutical company Eisai Co. developed a drug named Aduhelm and tested it in three large clinical trials in people with early Alzheimer’s disease. But the studies were halted in 2019 after showing no benefits. however, studies were revived after a new look at the data suggested that the drug reduced levels in the brain of the sticky protein called beta-amyloid.
When the protein accumulates, plaque is the chief cause of brain cell death and hence deterioration of patients. Aduhelm is the first drug shown to reduce the plaque.
“We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come,” said Biogen CEO Michel Vounatsos.
Dr. Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, said: “Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s.”
She added that approval would bring therapy to patients faster, while “spurring more research and innovation.”
The FDA gave the drug accelerated approval, a process usually reserved for treatments aimed at serious or life-threatening illness, based on the reasonable likelihood that it would produce benefits for patients. But the regulators required studies on the drug to continue for years to come, after its own regulatory committee recommended against approval last autumn.
Dr. G. Caleb Alexander, professor of epidemiology and medicine in the Johns Hopkins Bloomberg School of Public Health, served on the approval committee and told the Baltimore Sun: “There is an incredible amount of unmet need in a real sense, a palpable urgency for patients and their loved ones who may be experiencing the disease firsthand. But there is an enormous amount of uncertainty if the product works.
“Ultimately the FDA decided to allow approval of the product not on the basis of its demonstrative effectiveness in improving symptoms of Alzheimer’s, but on the ability to lower the levels of beta-amyloid.”
Shipping of the drug, which costs $56,000 a year, can begin immediately, but it is up to individual doctors whether they prescribe it. It’s not yet clear what stages of Alzheimer’s will respond to the treatment, and side-effets may include brain swelling, headaches and confusion.
Harry Johns, president and CEO of the American Alzheimer’s Association, said that the approval of Aducanumab was “a victory for people living with Alzheimer’s and their families”, and will give patients “more time to live better.” But he emphasised that the approval is not the end of the fight against Alzheimer’s, but rather “about reinvigorating scientists and companies in the fight against this scourge of a disease.”
Prof Bart De Strooper, director of the UK Dementia Research Institute, said that the decision to approve Aducanumab marked “a hugely significant milestone” in the search for treatments for Alzheimer’s disease, as in the past decade, more than 100 potential Alzheimer’s treatments have failed. But he warned that there were still many barriers to overcome, and Prof Robert Howard, professor of old age psychiatry at UCL, went even further, calling the approval of the drug “a grave error” that could derail the ongoing search for meaningful dementia treatments “for a decade”, and saying that the FDA had ignored data from the trial which showed no slowing of decline in cognition or function.
Alzheimer’s Research UK said it had written to the Health Secretary Matt Hancock asking the government to prioritise the approval process for the drug in the UK, but even with a fast-track approach, this may take 18 months.
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