Trial testing new avenues to prevent Alzheimer’s disease

Last month, a wave of excitement swept through the world of Alzheimer’s disease research after Lilly announced trial results for its drug donanemab.

The researchers found that the drug slowed cognitive decline in 47% of those who took the drug, compared with 29% of those who took a placebo. . “Delayed” here means that from 6 months he will be disease free for 1 year, as determined by multiple factors.

Donanemab, which is still in clinical trials, follows another drug from Japanese pharmaceutical company Eisai, lecanemab, which has been rapidly tracked by the US Food and Drug Administration. A third drug called aducanumab was approved by the FDA in 2021, JAMA Neurology As reported last October, donanemab and aducanumab were not ‘cost-effective’ given the limited cost and quality of life improvements.

What these drugs have in common, except that they are monoclonal antibodies (synthesized in the lab to mimic natural antibodies), are the brain cells that are thought to be most responsible for the disease. is to neutralize the accumulation of amyloid protein in Elevated amyloid levels lead to the triggering of another protein called tau that forms plaques and damages brain cells, leading to the cognitive decline typified by the disease.

An additional set of complications related to donanemab occurred in this trial. Donanemab, like lecanemab and aducanumab, can cause fatal cerebral hemorrhages and seizures.Nearly a quarter of participants in the Eli Lilly trial suffered from bleeding, and three died from bleeding.

The limited success of drugs that target amyloid protein accumulation alone suggests that there may be other factors that trigger the disease. One of them is the oxidative stress hypothesis, which states that the brain can be kept healthy as long as the ‘free radicals’ generated in the process of various biochemical reactions in the body are suppressed by ‘antioxidants’. This theory predates nearly a quarter-century of research into the causes of amyloid-related dementia, but recently researchers around the world, including India, have planned trials and treatments to test its implications. and is becoming more important.

Free radicals often damage healthy cells and are thought to play a role in a variety of diseases, including Parkinson’s disease. A variety of “antioxidant enzymes” are natural defenses against such unwanted oxidation. Superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase or aldehyde dehydrogenase, non-enzymatic antioxidant factors, etc. A 2013 study published in the same journal states that “antioxidant enzymes catalyze the reduction of free radicals, weakening the power of free radicals and thus reducing oxidative cytotoxicity.” Cycatria danubina.

As long as there is a balance between oxidizing molecules and the antioxidants that neutralize them, the body stays healthy. There are several of these antioxidants, but the representative one is glutathione.

This entity has a way of directly blocking free radicals and also maintains vitamins E and C in their reduced form, giving them antioxidant properties.

Dr. Pravat Mandal of the Manesar National Brain Research Center found that low levels of glutathione and high levels of iron and copper (which are highly oxidative) in the brain are associated with cognitive impairment in brain imaging studies conducted in his laboratory. associated with early signs. typical of Alzheimer’s disease. “Oxidative stress is present in everyone’s brain. As long as oxidative radicals are kept in balance by glutathione, brain function is fine. Scientists have speculated about these links for years.” But it wasn’t until my lab’s brain-imaging studies in Alzheimer’s patients showed reduced glutathione levels and oxidative build-up that I got more interest in this research,” he said. Hinduism. “My experience observing brain imaging of Alzheimer’s patients in various stages of cognitive decline has shown that glutathione deficiencies in key brain regions are marked and even associated with psychiatric problems. Oxidative stress is therefore a precursor to amyloid plaques.” ACS Chemical Neuroscience Last week we discussed the role of oxidative stress.

Later this year, Dr. Mandal and doctors at AIIMS in Delhi plan to begin a clinical trial to see if patients with cognitive impairment can benefit from 500mg of glutathione taken orally. Separately, his group is working with Gurugram’s Medanta Hospital to see if a blood test can determine if glutathione levels are extremely low in the brain, which is currently detected by magnetic resonance imaging (MRI). ) can only be determined.

Although the disease is irreversible once plaques form, identifying the conditions that cause these plaques could significantly improve life expectancy, Mandal said.

55 million people worldwide have dementia, the most common cause of which is Alzheimer’s disease. This number is expected to double every 20 years to about 78 million by 2030, according to estimates from Alzheimer’s Disease International. According to the India Dementia Report 2020, about 7.6 million people are expected to be affected by the disease in India by 2030, the majority of whom will likely be diagnosed with Alzheimer’s disease.

• What these drugs have in common, except that they are monoclonal antibodies (synthesized in the lab to mimic natural antibodies), are the brain cells that are thought to be most responsible for the disease. is to neutralize the accumulation of amyloid protein in

• The limited success of drugs that target amyloid protein accumulation alone suggests that there may be other factors that trigger the disease.

• An additional set of complications related to donanemab occurred in this trial. Donanemab, like lecanemab and aducanumab, can cause fatal cerebral hemorrhages and seizures.