14 May 2018

Genetics, technology, optics

Five newest ways to fight diseases

Discovery Channel, Naked Science

Man has earned the title of the crown of evolution: there are species that are better adapted, but only humans have achieved the greatest success in finding new ways of survival. Discovery Channel talks about innovative ways to fight diseases.

Tuk-tuk, Neo: A digital pill for insanity

Already this year, the innovative drug Abilify MyCite will go on sale – an electronic tablet that will allow you to track the schedule of taking medications in patients with reduced willpower. The joint development of the Japanese company Otsuka Pharmaceutical and the American company Proteus Digital Health is designed for people with schizophrenia, bipolar disorder, various types of depression and other mental disorders. Each tablet of an antipsychotic drug contains the active substance aripiprazole and a chip sensor. When the medicine dissolves in the stomach, the sensor is oxidized and sends a signal to the sensor attached by a patch to the patient's body.

Data on the dose of aripiprazole and when it was taken are sent from the sensor to the smartphones of those who control the schedule of taking pills: the patient will choose four people who will install the application and receive this information. The doctor, family and friends will be able to help the patient to be treated: if the signal does not arrive on time, they will call him and remind him that it is time to take medicine. The sensor is very small in size, harmless and is excreted naturally.

The release of Abilify MyCite has caused a lot of ethical controversy, but the FDA approved the "smart pill" in November 2017. The technology is planned to be used in the treatment of human immunodeficiency virus and senile dementia. According to WHO, senile dementia syndrome is now observed in more than 50 million people in the world, but regular intake of antipsychotic drugs can alleviate the symptoms, and with them the life of the patient's relatives. After all, a person with severe dementia does not recognize relatives, does not take care of himself and can be extremely aggressive, and with mild dementia, he remembers new data poorly and gets confused in time and space, which, in comparison with other symptoms, is more tolerable for both the patient and others.

Separate garbage collection: DNA against HIV

The search for a way to defeat the immunodeficiency virus in DNA itself began in 2003, when the American National Institute for Human Genome Research NHGRI organized the international research consortium ENCODE (The Encyclopedia of DNA Elements). Previously, it was believed that 20 thousand protein-coding genes account for only 1.5% of the genome, and the rest is "junk DNA", but ENCODE participants found out that the solution to one of the greatest medical problems of our time – the cure of the immunodeficiency virus - can be hidden in the "garbage".

When studying DNA, ENCODE researchers found sites belonging to ancient viruses – they embedded themselves in the genome to produce their own kind and cause disease, and then for unknown reasons stopped their activity, remaining immured in DNA. Now oncoviruses and human immunodeficiency virus behave in the same way: if you understand why their ancient predecessors stopped replicating, you can defeat HIV, Burkitt's lymphoma, Kaposi's sarcoma, lymphogranulomatosis, liver carcinoma and other diseases caused by DNA-containing oncoviruses. In the meantime, the matrix of these viruses is inseparable from the "junk DNA" and the task of scientists is to find a safe way to eliminate it without destroying the molecule.

The method of vaccination as a weapon in the fight against HIV is not suitable because of the highest variability of this virus and the special organization of the genome. As soon as the immune system adjusts to the antigenic portrait of the virus that is circulating now and suppresses its advantage, it receives a new version of the same pathogen. Now the copies of HIV produced by the matrix are suppressed with the help of antiretroviral therapy, but there is hope for victory over the viral matrix. In 2015, doctors transferred the disease from the category of fatal to chronic due to the use of a significant range of drugs that restrain the reproduction of the virus within the limits that allow the long-term existence of an infected person. In 2016, scientists from the Dresden Technical University created the Brec1 tool, which eliminated HIV-1 in mice – a more contagious and widespread strain than HIV-2. There is no data on successful human trials yet, but the main danger is that HIV is a retrovirus with a long incubation period: the longer the causative agent of the disease is in the DNA, the less likely it is to be defeated, and at the terminal stage, with AIDS, even a banal cold can kill a patient.

Put on, saw, measured: lens for hyperglycemia

As you know, with type I diabetes, daily monitoring of glucose levels is vital, and injections and tests are inevitable. Before the invention of the insulin pump, which both checks glucose levels and injects insulin, there was no alternative to injections and test strips at all, but not so long ago there was another tool for monitoring the condition of diabetic patients. South Korean scientists from the Ulsan National Institute of Science and Technology (UNIST) we created "smart lenses", taking into account the experience of colleagues from the company Verily, who developed the previous version.

Verily lenses had too large electronic components, and in South Korean all electronic elements are evenly distributed so as not to block the field of view. The cornea is protected by a layer of polymer, under which an ultra-thin sensor is located: it does not cause any discomfort, as proved by successful tests on rabbits, whose eyes are close to human in size. The principle of operation of "smart lenses" is based on the oxidation of glucose in tears under the influence of the glucose oxidase enzyme contained in the sensor: if everything is normal, the LEDs in the lens will work, but when the sugar level rises, they will go out, and the patient will realize that it's time to give an insulin injection. Perhaps the lenses will also be useful in the treatment of viral diseases – for this you will need to replace the enzyme in the sensor with the one that corresponds to the disease.

The idea of "smart lenses" for diabetics came not only in South Korea – the official Google blog also reported on such a development, when scientists from the Google X laboratory, led by Babak Parviz, associate professor of Electrical Engineering at the University of Washington and founder of the Google Glass project, created a lens with a sensor for every-second monitoring. Clinical trials have been successful, and while the product is being adapted for market entry, Google X is working on other projects. For example, smart glasses that will allow people with residual vision to transform light and movement into visual images and text. Stephen Hicks from Oxford University is in charge of this project.

Opium for the people: a vaccine against heroin

Methadone replacement therapy is banned in Russia, and in countries where it is still used, it is expensive and not always effective due to the fact that against the background of multi-day abstinence, the desire of drug addicts to be cured is often small or absent at all. A universal "withdrawal injection" has not yet been invented, but nevertheless there is already a way to alleviate the suffering of people who have decided to give up the use of opiates. Researchers at the Scripps Research Institute have created a vaccine that blocks chemicals for eight months, forcing the immune system to attack the molecules of heroin and the super-strong synthetic opioid fentanyl. Similar in structure to endorphins, they easily bypass the barrier between the circulatory system and the central nervous system, affect the m-opioid receptors in the brain and spinal cord and other organs and cause a state of euphoria. Mental and then physical dependence appears: with prolonged use, the m-receptors die off, and the body becomes resistant to the opioid, requiring an increasingly large dose of the drug for euphoria.

The vaccine of scientists at the Scripps Institute will give drug addicts immunity for eight months, and the main achievement is that with the introduction of the drug, psychological dependence will be destroyed: the patient will not only not feel the usual euphoria when taking heroin, but will also be protected from overdose. To create a vaccine, a heroin molecule was combined with a carrier protein and an adjuvant that increases its effectiveness. Out of twenty options, the best combination in terms of efficiency and stability was chosen – tetanus toxoid and aluminum alum. The drug retains its properties for 30 days – this allows it to be transported and tested on humans, and tests on mice and rhesus monkeys have already been successful.

An antiheroin vaccine is also being created in Russia: last year, researchers at the National Research Center for Narcology announced successful trials of a drug that does not allow the drug to pass to the central nervous system due to the production of antibodies, like the American counterpart. The researchers said that the vaccine will be effective for a year, but so far it is causing more controversy than approval, as was the case with the "smart pill" for schizophrenia. Another nuance is that the treatment of dependence on morphine, heroin, desomorphine and other drugs of the opium group is complicated by the patients themselves: drug addicts often endure detoxification for 20-40 days so hard that they break down only for the sake of ending the torment.

Cancer editing: Gene reprogramming of cells

Vaccination will help both drug addicts and cancer patients: there is already evidence that drug treatment of cancer and its prevention are possible. In early March, the authoritative portal Medicalexpress reported that scientists from the University of Michigan combined Qß particles (crystalline bacteriophages of Escherichia coli coli) with carbohydrate antigens of TAS (tumor-associated carbohydrate antigens), which provoke the growth of metastases. The resulting vaccine can slow down the growth of cancerous tumors and prevent the formation of new foci of the disease. Whether this is true or not, experiments on dogs with osteosarcoma, which people also suffer from, will show, and if successful, veterinary medicine will also move forward.

The chances of a positive outcome of the trials are high: T-lymphocyte-based gene therapy already exists. In August 2017, the FDA approved the drug Kymriah from the American company Novartis, which helped dozens of people to cure lymphoma. In the experiment, 81 patients from different countries had their T-lymphocytes taken away, reprogrammed in the laboratory and injected again into cancer patients. The trigger for lymphocytes was the cancer tumor protein CD19: T cells attacked metastases, destroying them, and 73% of patients from the focus group were cured of recurrent diffuse B-large cell lymphoma in six months - this is a very significant success.

Tests on the use of gene therapy in the treatment of follicular lymphoma (71% recovered) and leukemia were also successful – in the latter case, the drug is made individually and each reprogrammed lymphocyte can kill one hundred thousand cancer cells. Drug prevention of cancer is also possible: it has been proven that the HPV vaccine Gardasil 9 from Merck & Co, which is licensed in more than 60 countries around the world, can protect against nine genotypes of human papillomavirus and genital cancer in 97.4% of cases. Another latest development is the FDA–approved drug Keytruda for the treatment of tumors associated with individual biomarkers: its active substance pembrolizumab affects disease foci in more than 10 parts of the body. All this makes cancer treatment more universal, but so far it is prohibitively expensive for many patients: for example, in April, foreign media reported that the annual course of the drug Kymriah costs 475 thousand dollars.

At the speed of light: ultraviolet against the flu

Ultraviolet radiation accelerates chemical and biological processes, which has been actively used in medicine for a long time, but in February 2018 it became known that ultraviolet radiation can be safely used to fight viral infections. The rays of the "long" part of the short-wave range (far–UVC with a wavelength of 207 nanometers), penetrating into the upper layers of the skin, successfully inactivate the action of viruses - and do not have a carcinogenic effect, as was believed until last year. Scientists at Columbia University Medical Center have proved that far-UVC radiation can be effectively used in the fight against A (H3N2) strains and B/Yamagata, which turned out to be stronger than vaccines this winter and raised a wave of flu cases in Europe.

The center's researchers claim that far-UVC rays are as effective as bactericidal ultraviolet lamps, but, unlike them, they are safe – this has been confirmed by successful studies. The H1N1 virus strain was irradiated with a lamp with a wavelength of 253.7 nanometers and UV rays with a length of 222 nanometers, while far-UVC destroyed the influenza virus without "side" mutagenic effects. The authors of the study believe that humanity should use all the possibilities of a new tool in the fight against influenza: it acts on all strains, which means that harmless ultraviolet irradiation of crowded places during an epidemic can significantly reduce the spread of viruses.

Flu is not at all a severe type of cold, as many believe: this deadly virus, which can infect anyone, leads to three to five million cases of infection and 250-500 thousand deaths worldwide every year. People are finding new ways to fight infectious agents, and this gives hope for victory over them – at least temporarily, as in the situation with the outbreak of Ebola in Central and West Africa in 2014. Viruses mutate, and there is no guarantee that humanity will be able to defeat the flu in the same way as smallpox, which in the Middle Ages mowed down entire cities and peoples. What are the chances of people in the battle with invisible killers, a new Discovery Channel project dedicated to the three most dangerous viruses – smallpox, influenza and Ebola will tell. In the program "Viruses" you will learn what people have learned while fighting infectious agents, what role viruses have played in the development of civilization – and what else they can play.

Watch the program "Viruses" from May 16 on Wednesdays at 22:00 on the Discovery Channel.

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