An under-investigation drug has resulted in reduced cognitive decline in patients with early Alzheimer’s, promising to become one of the first neuro-protective therapies for the disease. The companies, Eisai and Biogen, recently announced the results of a phase III trial conducted with 1,795 participants, who already had plaques of the protein called amyloid in their brains.
The yet-to-be peer-reviewed report showed that there was 27 per cent less decline in the cognitive function of people who took the medicine Lecanemab as compared to those who did not after 18 months. The cognitive decline of the study participants was measured on the DR-SB: Clinical Dementia Rating-Sum of Boxes scale that assesses performances of the patient in six areas — memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.
Why are the findings significant?
“This is probably the very first drug that has claimed to slow the progression of the disease. At present, the treatment for Alzheimer’s is mainly symptomatic. There are a few pills that improve memory in early stages but they do not help in the other facets of Alzheimer’s. There is certainly a need for such neuro-protective drugs for dementia and there are several drugs in the pipeline,” said Dr Rajendra Dhamija, a neurologist and director of the Institute of Human Behaviour and Allied Sciences (IHBAS).
He, however, added the rider that the current trial provided very limited data for the drug to become standard practice. He said there was a need for much larger scale study with various population groups to show that medicine is effective across populations.
The increasing lifespan and very high burden of diseases, such as diabetes, hypertension, and obesity, are expected to “dramatically” increase the prevalence of dementia in India, according to a 2021 Nature study by researchers from the Indian Institute of Science. Dementia is an umbrella term for a group of disorders that lead to impaired memory, decision-making and social skills – Alzheimer’s is one of the most common types of dementia.
The Dementia in India report 2020 estimates that there are 5.3 million people over the age of 60 years living with dementia in India, with the prevalence projected to increase to 14 million by 2050.
“Drugs such as this or many others under development may not do much for those who already have full-blown Alzheimer’s but such drugs may reduce the incidence in the future,” said Dr Pravat Mandal, a medical physicist and scientist at the National Brain Research Centre.
What do the findings tell us about the theories on what causes Alzheimer’s disease?
Not only have several therapies for Alzheimer’s and other dementia – a group of neuro-degenerative diseases –failed to achieve result over the years, scientists still do not agree on what causes the disease — pathological clumping of amyloid protein, autoimmunity, or high levels of iron in the brain are among several proposed hypothesis.
The researchers have claimed that the success of Lecanemab — drug that selectively binds and neutralises toxic beta amyloid aggregates – proves the amyloid hypothesis. This theory posits that abnormal accumulation of the beta amyloid in the brain is one of the main causes of Alzheimer’s disease.
Many others have claimed the disease to be auto-immune in nature, with the beta amyloid cell in fact playing an important role in the defence of the brain from bacteria. The problem occurs when the cells cannot tell the difference between the fat molecules that make up the envelopes of the bacteria and the brain cells and end up attacking and damaging the brain cells.
Dr Mandal explains that the changes occur because of the increase in iron levels in the brain. He said, “The amyloid malformations are in fact a consequence and not a cause of the disease. The disease as well as the amyloid malformation occurs when there is an increase in the levels of iron in the brain and the depletion of the primary antioxidant, glutathione.” He said glutathione can bind with the free iron and prevent the build-up along with other features of Alzheimer’s.
“The solution is very simple – we just need to give people with mild cognitive impairment an iron chelator (a substance that can remove the excess iron) along with the glutathione supplement. The supplement is already available in the market but people never thought of its benefits for the brain till now,” said Dr Mandal. His lab is set to begin a clinical trial October onwards to prove this hypothesis. “We will have to show that the drug actually enters the brain and that there is a protective effect. No drug will probably be able to cure Alzheimer’s, our aim will be to keep delaying it,” he said.
Other than medicines, what can be done to prevent Alzheimer’s?
Non-communicable disease such as diabetes, hypertension, and obesity are all risk factors for Alzheimer’s, so efforts to reduce these factors such as daily exercise, healthy diet, quitting smoking, and good sleep can go a long way in reducing the risk of the disease.
Other than that, doctors suggest that people, especially the old and those with family history, keep their brains active and engaged.
“Learning new languages, developing hobbies like music, solving puzzles like Sudoku keep the brain active and cognitively fit. It is also important for the elderly to go out, make new friends and socialise,” said Dr Dhamija.