Team:NJU-China/Practices

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    Interviews and Propagation

    The perspective of our therapy has always been the major concern since we started our project. We kept thinking whether our therapy could be applied clinically or really help patients who suffer from drug abuse in terms of drug effects, expense, etc. Thus, we decided to consult the policemen, patients, neurobiologist and doctors about the feasibility and clinical appliance of our project. On the other hand, we went to communities on International Day Against Drug Abuse to propagate that all people should keep away from drug. Also we appealed people to refuse drugs and ultimately we got 528 signatures from people who declared their determination to fight against illegal drugs.



    Interview at rehab


    Location: Women forced quarantine rehab of Jiangsu Province

    Present situation:
    Capability of the rehab is 2000 person, but it still can’t satisfy the magnificent needs. It applies semi militarization management, including laboring and psychological counseling on a daily basis. Rehab is short-handed in policemen, and the average patients that one policeman take charge of are over 10.

    Vice superintendent:
    1. The rehab is established by government, since policy nowadays strongly supports rehab projects. But due to the problem of personnel organization, now rehab is relatively short-handed.

    2. Rehab applies the quarantined method. Common drugs can be detoxed within a week, but heroin requires relatively longer time period. It takes about two years for patients to rejoin the society, but relapse rate is pretty high, especially for heroin. Many people went in an out for six or more times; some even relapsed within 24 hours.

    Director (in charge of psychological counseling)
    1. She mentioned that our project aims at curing physical pleasant sensation, but it should cooperate with psychological counseling as well.

    2. She claimed that the cost of our medicine is pretty high, especially for individual cases. He suggested that we can start from patient who is well-off and not so heavily addicted.

    3. Withdrawal reaction of heroin is quite severe, so that some drug addicts tend to violate laws to get heroin.

    4.Now ratio of infecting AIDS from drug taking is high. Ratio of juvenile drug taking is also rising, and the lower age limit drops from 17 to 15

    Policeman:
    1. If our medicine could bring some terrible or even disgusting feelings to drug addicts when they are taking drugs, it may be more effective in preventing relapse.

    2. Addiction of methadone is actually stronger than heroin. It is not the ultimate cure but just a method of using drugs with less toxicity as a substitute.

    Patients:
    1. Using methadone is not a desirable choice. It is addictive, and its physical reaction when addiction seizures is bigger than heroin’s. Some patients even choose relapsing heroin to relieve physical pain brought by methadone.

    2. Patients accept our medicine which could cure physical pleasant sensation of relapse, and don’t mind about GM medicine, for detoxification is of utmost importance.

    3. The costs and side-effects are their central concerns. If the medicine is expensive, then it will lose the possibility of wide promotion. Even though patients are willing to try, it will be too costly to use. On the other hand, patients oppose medicine that has strong side-effects, for their physical conditions are already seriously damaged by drugs.

    4. They claimed that central reason for relapse is not for physical dependence, but psychological one. Some people relapse because of feeling of emptiness; some rejoin former addicts crowd; some think luckily that a single one time is safe from addiction or prison.

    Final reflections:
    1. Detoxification needs concerted efforts from society, community and family, in which psychological withdrawal weighs most. Our medicine aims at curing physical addiction as much as possible. As for psychological part, maybe we can enable our medicine to bring disgusting feelings to medicine-takers when they take drugs, or maybe we can research on the psychological dependence of brain in the future.

    2. Acceptability of our project is quite high from policemen and patients, and they have high expectations for the medicine to pass through clinical trials and enter the market as soon as possible. This strongly illustrate our project has profound meanings.

    3. As the most widely used medicine for detoxification, methadone is not so ideal in patients’ eyes, and their addiction is even stronger than drugs. As a consequence, research of new detoxification medicine is urgently needed.

    4. Trend of abusing methamphetamine is rising, which requires society to voice out its tremendous danger. Some people use methamphetamine to get rid of heroin. Even though they were addicted to methamphetamine, the reaction of heroin did relieve after taking methamphetamine. That makes us wonder if there exists counteraction at the site of action between heroin and methamphetamine, and if a medicine imitating methamphetamine could be designed, which also have the ability to substitute heroin, but dose no damage to the brain and is also safe from addiction. Due to the unawareness about addiction mechanism of methamphetamine, designation of such medicine could begin after the whole process is unfolded.

    Interview with neurobiologist


    We consulted two neurobiologists, Professor Jian Jing and Professor Liang Li from Nanjing University, to help us evaluate our project from a more academic perspective.

    Professor Jing first praised us for creativity and novelty of our project and for our brilliant job done in terms of difficulty of our project. Nevertheless, both of two neurobiologists point our several defects of our project to help us direct the future work.

    Although our therapeutic exosome is capable of delivering siRNA into brain after proper modification, it fails to distinguish specific regions in the brain. The ventral tegmental area (VTA) in the midbrain contains dopaminergic neurons and is responsible for opioids reward. Downregulating the level of MOR protein in other regions of brain may bring about severe safety problems because MOR is indispensable of pain relieving. Professor Jing recommended us to further modify exosome so that it can be directly and precisely targeted to VTA in the midbrain.

    Professor Jing also casted doubts on whether our therapy could work on the human beings although our experiments on mice were effective. There are many cases where drug effects tested on animal models are inconsistent with effects tested on human beings.

    Professor Li argued that we should consider culturing primary neurons in vitro because these cells can give more authentic feedback. Neuro2A cell line we tested in our experiment is immortalized and differs from cells in real situation.

    Other questions include whether downregulating MOR with the efficiency of 50% is sufficient to suppress the rewarding effects? We tried to answer this question using both computational and experimental methods, and the details of which are available in modeling and experiment sections.

    Finally, we need to redesign siRNA because the siRNA we currently used is designed to target mouse MOR gene. We should also consider the safety issues concerning immune response caused by other proteins encapsulated in exosomes when applying our therapy clinically.

    Interview with doctor


    We visited our local Methadone Clinic in Jinshan Hospital, Nanjing. Doctor Guangwei Geng was very generous with his time, sharing his opinions on the current situation of drug abuse and clinical challenges he met, as well as comments about our project with our team members.

    Doctor Geng first introduced the situation of drug abuse, specifically of heroin abuse in Nanjing. The statistic has shown that over 2,000 people are registered as heroin abusers out of a total population of 8 million, demonstrating that drug abuse, especially involving heroin or other opioids, is still a severe problem which is urgent to solve.

    We then shared our knowledge on the mechanism of opioids addiction and the principle we based on to develop our therapy with Doctor Geng. Doctor Geng believed that the current therapy of drug detoxification is quite limited because we know nothing about drugs, other than opioids, of mechanisms underlying addiction or current existence of any possible treatment methods. He held a positive view on our project, indicating that our project provided a brand new approach to dealing with treatment of drug addiction and can have a potential for further application.

    However, Doctor Geng also pointed out some drawbacks of our therapy, giving us clues on improvement of our project. The high expense of our drug may impede the progress of further clinical application. We have carefully examined this problem and figured out some potential directions in our future work section.

    Doctor Geng recommended us to perform clinical trials as soon as possible because we, at present, merely have data on the basis of mice experiments. He also guided us on the recruitment of volunteers to perform clinical trials. He suggested us to focus on patients addicted to morphine first and also give priority to those who develop a slight degree of addiction. As stated by Doctor Geng, the effect of our therapy is more explicitly observed in this group of people. In addition, under the circumstances that the government encourages to accelerate the development of drugs for detoxification, we have to be familiar with the standard procedure of administrative examination and approval.

    Human practice in International Day against Drug Abuse

    We have already known that the drug does harm to our human society. According to that, our team wishes to expand the value of our project to help solve the drug problems. We did some human practice to propagate the harm of drug. Furthermore, we try to figure the problem out on clinical treatment in order to find a new medicine for drug addiction. Firstly, we made some brochures that include the introduction of various drug, the existing methods of drug treatment and terrible instances of people who addicted to drug. With those materials, we went to communities on International Day Against Drug Abuse to propagate that all people should keep away from drug. Also we appealed people to refuse drugs and ultimately we got 528 signatures from people who declared their determination to fight against illegal drugs.


    Figure 1. (a) One of the brochures made by ourselves that introduce drug. (b) Introduction of the existing methods of drug treatment and instances of people who addicted to drug. (c) Introduction of Methamphetamine in our brochures. (d) The brochures we made to show our project.

    Figure 2. Our propagation in communities in four Districts during three days.

    Figure 3. We appealed people vary from kids to old men to sign for refusing drug.

    Figure 4. The signatures we collected for rejecting drug.