21 September 2017

"The mad Man"

How the World resists Alzheimer's disease


September 21 is the World Day against Alzheimer's Disease, which takes more and more human lives every year. Yuri Deigin, Vice-president of the Science for Life Extension Foundation, talks about how science is trying to defeat it.

"Alzheimer's disease is me, who ceases to trust myself, a laughing stock for my own jokes, periodically unable to cope even with such a banal task as finding slippers. It is impossible to fight this, you should not have false hopes for the honorary title of “survivor”. The disease steals you from yourself," said the famous English science fiction writer Terry Pratchett about the diagnosis that killed him at 66 after 8 years of struggle.

As "senile dementia of the Alzheimer's type" develops, as doctors formally call it, neurons gradually die in various areas of the brain. First, the targets are those that are responsible for short–term memory, then for long-term memory, and so on. So, day after day, a "reasonable person" loses his mind and turns into a madman: the disease erases his personality, leaving only a physical shell. However, she also dies after eight to ten years, when Alzheimer's gets to the life support systems and turns them off one by one.

A graduate of the Central College of Art and Design offered to get an approximate idea of how people with acquired dementia feel. Saint Martin (Central Saint Martins) Di Peng, who designed a special helmet for this. His visor affects your vision, you can hardly distinguish the faces of your loved ones. Imitation of auditory hallucinations does not allow us to perceive reality adequately, and finally, a special microphone makes speech difficult and changes the spoken words, depriving them of meaning. Thus, you are almost unaware of what is happening and practically lose the opportunity to communicate with people.

In fact, this helmet is a rehearsal of what awaits many of us abroad for 60 years: at this age, 5% of people have Alzheimer's, 30-40% of 80–year-olds are already ill, and by the age of 90, this pathology is already observed in almost 50%. And there is still no panacea for it.

The scale of the problem

Over the past decades, medicine has stepped far forward and demonstrated impressive successes in various fields: scientists and doctors have found ways to prevent, bring into remission and even completely cure once invincible diseases, simultaneously increasing the duration of human life and, as a result, the number of elderly people: today there are already a billion people over 60 years old on the planet, by 2030, there will be 1.4 billion, and by 2050 – 2.1 billion.

The downside of these successes can be seen in the latest information reports of the World Health Organization (WHO): among the 10 leading causes of death worldwide, Alzheimer's disease and other types of dementia have risen to the 7th place. It is significant that back in the early 2000s, this place belonged to HIV and AIDS, which are now not even in the top ten.

Given that there is no effective therapy or prevention of acquired dementia yet, the scale of the upcoming epidemic is frightening. Already today there are almost 50 million patients with Alzheimer's or similar dementia in the world (in some countries only general age-related dementia is diagnosed), and by 2030 this figure will grow to 75 million.

The chances of remaining "sane" are melting every year, and the notorious senile senility has long ceased to be a cause for jokes. If we are unlucky enough to die from cardiovascular diseases or other leaders of the WHO rating, then with a high degree of probability we will face a slow, painful and humiliating death from Alzheimer's disease, which accounts for 70% of all cases of dementia.

Tolling of the alarm

"All I could think about was, 'I know three people who have seen improvements since the discovery of a brain tumor. I haven't heard of anyone who got better after being diagnosed with Alzheimer's," he recalled Terry Pratchett on the day he was diagnosed with the disease.

This is still the case: scientists do not yet have a complete understanding of the mechanisms of Alzheimer's pathogenesis. One can only single out some factors that increase the likelihood of developing the disease.

For example, people who expose the brain to negative physical effects are at risk: football players or boxers. There are studies that show that the development of dementia may be associated with insulin resistance in the brain, some scientists even call Alzheimer's "type 3 diabetes". At the same time, people who suffer from ordinary diabetes are much more likely to be affected by Alzheimer's disease. However, to hope that a healthy lifestyle will guarantee to avoid this fate, alas, is not worth it: Alzheimer's sufferers and Zozhniki.

There are also no means that could cure or at least slow down the disease. The drugs approved to date are acetylcholinesterase inhibitors. They help to make up for the lack of acetylcholine (a neurotransmitter that transmits signals between neurons) in the brain, which is observed in the pathogenesis of Alzheimer's disease.

This makes it possible to slow down the development of the disease by only a small percentage, as well as to give at least a little hope to patients and their relatives. However, the stigmatization of mental patients and the fear of being branded "feeble-minded" lead to the fact that older people often hide their forgetfulness and other changes, which are usually the first symptoms of the disease, and as a result do not receive even this minimal help.

Scientists and doctors around the world understand the catastrophic situation, and therefore they sound the alarm, and they are given billions of research grants. Thus, the budget for the study of Alzheimer's disease in one of the largest organizations funding scientific research, the American National Institutes of Health (NIH), in 2017 will amount to almost $ 1.4 billion.

Big Pharma vs Alzheimer's

Despite the attention focused on Alzheimer's disease and the enormous amounts of funding allocated, scientists are still losing in this fight: from 2002 to 2012, only 1 out of 244 candidates for registration of a drug for this disease received FDA approval and joined the ranks of safe, but not too effective acetylcholinesterase inhibitors.

Nevertheless, the battle continues: researchers are trying to combat individual manifestations of the disease and hope that they may be the cause of its occurrence. We are talking primarily about the accumulation of amyloid plaques (from beta-amyloid peptide) and neurofibrillary tangles (from tau protein), which were found in the brains of patients.

Alas, the most popular approach today, associated with the elimination of beta-amyloid plaques, has not yet met expectations. Leading pharmaceutical companies have been trying to defeat the "bad protein" for many years, but one by one they report failures. Among them, for example, Merck, Pfizer, Johnson & Johnson and Elan Pharmaceuticals. However, there is still hope that Big Pharma has something else in store in the pipelines. Research continues.

Another approach to therapy is associated with a genetic predisposition to the development of Alzheimer's disease: one of the three alleles of the apolipoprotein E gene repeatedly increases the risk of this dementia – carriers of two copies of this allele may have a 91% chance of Alzheimer's, and the average age of its diagnosis is 68 years. However, firstly, even the absence of an ill-fated allele does not guarantee that the development of dementia will be avoided, and secondly, it is unclear how to help those who have this allele. So while the "genetic" approach to Alzheimer's therapy is not popular. Perhaps the situation will change as gene therapy improves.

A new hope

"There is a good way to avoid Alzheimer's disease – to die at the age of 30," he said Pratchett.

Given the history of failures of various approaches to therapy, it is difficult not to see a fair amount of truth in the writer's gloomy joke: it is not for nothing that this deadly pathology belongs to the class of "age-dependent", such as cancer and cardiovascular diseases.

The fact is that as the body ages, it gradually loses the ability to maintain homeostasis, which eventually leads to a number of diseases and then to death. This systemic degradation begins from the moment of puberty, and the first twenty years proceed almost imperceptibly, but inexorably. Little by little, our muscles atrophy, vision and hearing deteriorate, the immune system ceases to properly perform its functions – it is possible to list the "companions" of this pathogenic process for a long time.

The most unpleasant thing is that cognitive functions begin to decline from the age of 25, and then the "sword of Damocles" of dementia rises above our head. Moreover, every 10 years we lose about 5% of the volume of brain matter: by the age of 80, the brain weighs about a kilogram, whereas in 20 years it weighs one and a half. In many people, these processes lead to the development of Alzheimer's or other dementia. So, if we could return the body to a younger state, then the threat of Alzheimer's disease would recede.

It sounds like science fiction, but scientists have been working for a long time to make this a reality.

In search of Aging Therapy

Gerontologists are confident that aging can be defeated or at least slowed down. The latter has already been successful in the course of successful life extension experiments for dozens of different species of model animals – from worms and flies to mice and primates. For example, during one of them, specially bred fast-aging mice lived 30-50% longer, depending on the control group.

It also gives optimism to the existence of animals in nature with the so-called "negligible aging": the risk of their death practically does not increase with age, and they die with the same frequency at any age, unlike humans. In addition to thousand–year-old trees or well-known long-lived turtles, an example is the bowhead whale, which lives for about 200 years, or some species of perch, which are almost as good as him in this.

More and more researchers are involved in the fight against aging as the root cause of all age-dependent ailments and are trying to change our biology. These include, for example, the teams of the Buck Institute for Aging Research and the Salk Institute, as well as a number of startups: a subsidiary of Google (which has since been transformed into Alphabet Holding) purposefully created to combat aging under the name California Life Comany, or Calico for short, the company of the pioneer of genome decoding Craig Venter, Human Longevity Inc., Ambrosia and Unity Biotechnology companies, in which the open transhumanist Peter Thiel and others invested.

Let's hope that their efforts will be crowned with success. After all, in this case, we will be able not only to get rid of the threat of age–related pathologies, but also to radically prolong a healthy human life - then we will not have to die either in 30 or 80 years.

Portal "Eternal youth" http://vechnayamolodost.ru  21.09.2017

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