IPS Cell Technology

Today’s Close-up, IPS Cells

“Today’s Close-up” can tell you the things about what is happening in Japan right now. Sometime it picks up a bright topic, and sometime it talks about a dark topic. My estimate is 20% of the bright ones and 80% of the dark ones. That doesn’t have to make you feel so pessimistic about our society in Japan. In another word, if the society has lots of problems, should there are a bud of a chance to change our society for a better future. If individuals who are aiming for social entrepreneurs, “Today’s Close-up” is about a program that gives a chance to find the seeds of the business.

If you say, there are entrepreneurial opportunities in eliminating the frustration of our customers; I think social entrepreneurs should notice that it is frustrating that society suffers. And social problems have been recognized by many people once, individuals or NPO, even private companies providing a method of solving those issues have been presented in our society, we, society, municipality, and country, should support and continue to operate by applying.

Japan is a country of improvement and reform. Individuals, who is thinking even if there are any problems, exist and try to find out the solutions. We will be aware of such individuals! Cheer such individuals! “Today’s Close-up”, is providing so many hints to improve the Japanese society.

IPS Cells, New Horizon in Drug Development

Scientists of this lab are speeding up habits to develop a new drug to treat Alzheimer’s disease.This is T-817MA. Technology using induced pluripotent stem cells are IPS cells plays a key role.

The researchers are using IPS technology to develop new drugs to treat various diseases. The drug could promote the growth of bones in patients with Skuffle dysplasia. Skeletal dysplasia is a term for a group of rare diseases that have non-known-cure.

Mother {If there is a drug that can help her, all the inconvenience she endures will disappear.}

A group of Japanese researchers on Thursday announced a result of studies that could be a big step forward in developing such a drug. The researchers took a new approach. They used IPS technology to recreate the condition of the disease. Then tested the effects of various drugs.

Researcher {We were able to make this discovery thanks to IPS technology.}

IPS technology said to have opened a new horizon in drug research. We will look at what’s happening in the cutting edge drug development.

Drug Development Using IPS Cell Technology

Welcome to today’s close-up. Researchers last week conducted the world’s first transplant of retinal tissue derived from IPS cells. The subject was a patient suffering from a serious eye disease. People often associate IPS cells with regenerative medicine that we now know IPS cells have a great potential to help a lot of patients by facilitating drug development. Kyoto University researchers say they have identified a substance that could be used to treat patients with skeletal abnormalities. The research involved IPS cells created from the skin cells of the patients. This is a totally new approach to drug development. The researchers say they will start clinical trials within the next two years.

The researchers create IPS cells by putting certain genes into mature cells. IPS cells can be turned into almost any kind of cells, such as neuron, blood vessels and heart muscles. They can also help drug development. IPS cells created from the patient’s own cells can be created in the lab dish disease affecting the patient. That’s how the Kyoto team identified substance that may work as a treatment for skeletal dysplasia. IPS cells could soon create a new horizon in drug development. But many pharmaceutical companies say it is still early days in the field of cell technology. The Kyoto University team’s achievement may change that. If it’s research succeeds in delivering effective drug to patients who needed, drug development using IPS cell technology will take off.

Skeletal Dysplasia

Sakata Urata  is a second grader the city of Wakayama, in western Japan. She suffers from skeletal dysplasia. This rare disease stops the growth of limbs for the formation of the degraded cartilage. Her mother Hiromi places tools around the home to help her reach things. The disease often has complications. She suffers from inflammation of the middle ear and sleep apnea syndrome. The treatment now available for patients with skeletal dysplasia involves a series of surgical procedures. The bone in the patient’s limb is cut in two, the separated parts are placed slightly apart from each other. That’s how the bone regenerates to fill the gap to make the limbs longer.  This is an extremely painful procedure. Hiromi is looking forward to the development of a  painless treatment for her daughter.

Mother {If there’s a drug that can help her, all the inconvenience she endures will disappear.}

Kyoto University center for IPS cell research and application have been trying to develop just such a drug. They began discussion on a research proposal earlier this year. Professor Noriyuki Tsumaki has been working under Professor Shinya Yamanaka, who created human IPS cells seven years ago.

Yamanaka {If a drug proves to be effective, it will help improve the patient’s condition. I think you should start preparations.}

Tsumaki started by re-creating skeletal dysplasia the cellular level in a lab dish. His team first creates IPS cells with skin cells  taken from the patient, then convert them into cartilage tissue.

Researcher {These are the cells in precartilage state.}

IPS cells created from the patient’s own skin cells contain a gene responsible for causing skeletal dysplasia. The presence of the gene allows replication of the disease and cartilage grown in a lab dish. IPS cells have been cultivated for 90 days and converted into cartilage tissue. Normal cartilage tissue turns red when a reagent is applied. This tissue does not. That means it’s an abnormal growth of cartilage replicated in a lab dish. The replicated diseased tissue is expected to make a much more efficient development of effective drug. Until now, the first stage of the drug development is involved tests on animals such as mice. But all too often, the drug that works well on mice didn’t work on humans. If IPS cells created from human can be used to check the efficacy of drugs on the development. That would be no need to test them in mice.

Tsumaki {This will be a whole new approach to drug development.}

It is easy to create a large number of cells represent a replication of the disease in question. So it will be easy to try out a wide selection of potential drugs during the process. This will allow researchers to randomly test a wide variety of drugs. By trial and error, Professor Tsumaki made a very interesting discovery. Statin is a drug which lowers blood cholesterol level. The drug is widely used to people suffering from heart diseases. Professor Tsumaki became interested after he learned that statin can also increase the bone density of people with osteoporosis. He put statin in replicated abnormal cartilage cells in the lab dish. It cultivated them in two months. When Professor Tsumaki applied reagent, the tissues turn red. That show the cartilage tissue was growing healthily.

Tsumaki {I didn’t think the drug would correct the abnormality so well.}

He tried statin on mice. It worked.

Researcher {These are mice suffering from the disease.}

Statin was given to the mice. Two weeks later, the length of their bones was measured.

Researcher {It is 9.266 mm.}

Reporter {Isn’t that within normal range?}

Researcher {Yes.}

The mouse on the right was given statin. The mouse has grown larger than the mouse on the left, which wasn’t given the drug. The legs of the mouse on the right have grown to almost normal length.

Tsumaki {The bones of the mouse have grown. The drug could work for people with this disease. Without IPS cells,  we wouldn’t have been able to find this out.}

Recreate The Biology Of The Disease

Kuniya, Host of TV Program {Joining us today is Professor Shinya Yamanaka. The planned clinical trial is likely to be the first time in Japan that drugs made with IPS cell technology and use the humans.}

Yamanaka {When Professor Tsumaki first came to me with his research data,  it has been just as shocking as when I first succeeded in creating IPS cells. Until now,  the pharmaceutical industry has seen drug development as something that requires huge amounts of time and money. We need to change this preconception. This conventional mindset. I’m especially excited about Professor Tsumaki’s discovery using IPS cells. It could become a significant and successful example of how to trigger change in that mindset.}

Kuniya {So what you mean is the conventional drug development methods used by pharmaceutical companies have prevented effective investment and research.}

Yamanaka {This established process of drug development is to find molecules that cause the disease and to make drugs that detect those molecules.  But by using IPS cell technology, we don’t target the molecular course. Instead, we recreate the features of the disease and look for drugs to suppress the symptoms.  It’s a new approach. We use IPS cells to recreate the biology of the disease. This method doesn’t allow us to understand the molecular mechanism behind the disease. But we can put that problem aside for now. If something can treat a disease in IPS cells taken from patients, then it is very likely  it will also work on the patients. It is that kind of major change in mindset. Professor Tsumaki’s research also breaks with preconceptions because he began working with cells from human patients, not mice. After he found that statin was effective in human IPS cells,  he proved it worked in mice just to make sure. But to be honest,  I don’t think he needed data from mice to  verify his findings.}

Statin-Based Drug

But there is still a long way to go before statin-based drug to treat skeletal dysplasia becomes available. Statin had developed to treat adults. There is a little danger about whether safe to use these drugs to treat children as a fear of serious side effects. Professor Tamaki and his  team hope to start clinical test on a statin-based drug  within the next two years. They will carefully study the appropriate dosage and administration method for children.

Yamanaka {The Statins now available to us were designed to lower cholesterol levels in adults. Oral administration of statins to children suffering from skeletal dysplasia could cause side effects. Very few positive effects could be expected. We must first carry out clinical trials to optimize the use of statins in children that includes how to administer them.}

Kuniya {But how can you tell whether the disease pathology we created an IPS cells is the same as in the patient?}

Yamanaka {That is a very important question and a difficult one. In the case of cartilage we are  pretty confident that IPS cells can reproduce actual conditions. Cartilage cells are very simple. It is relatively easy to recreate them outside of the human body. But when it comes to diseases more complicated organs such as the nervous system and the brain. We need to accumulate more data. We have to find out how closely IPS cells can externally reproduce how the disease actually affects patients.}

Kuniya {How widely can this technology be applied? Can it to be used only to develop drugs to treat congenital genetic disorders?}

Yamanaka {The technology can be applied if we can reproduce the disease pathology using IPS cells taken from patients. That means it can probably be used to treat genetic disorders caused by a single or limited number of genes. Many of the so-called incurable and rare diseases are potential targets for drugs developed using IPS technology, and scientists have found that more common illnesses such as Alzheimer’s and manic depression can also be reproduced using IPS cells. Those two diseases also candidates for developing drugs using IPS technology.}

Amyloid Beta Protein

IPS cells, helping researchers find out how Alzheimer’s disease develops in human brains.

The Professor Haruhisa Inoue of Kyoto University’s IPS research center studies cerebral neurons. He and his team produced IPS cells from the patient’s skin. They successfully recreated cerebral neurons affected by Alzheimer’s disease. The black-yellow part showed  amyloid beta protein. The scientist believes a build up of this protein in neurons destroys the cells. But Inoue’s team that found that  wasn’t necessarily true.  They analyze neurons created from IPS cells from several patients skin cells. They found conditions differed among the patients.  They discovered at least three different ways amyloid beta protein builds up.

Inoue {Like most researchers, we had believed that amyloid beta protein would accumulate inside the neurons, but we were wrong. We might be able to identify more patterns.}

T-817MA

The discovery has dramatically changed how  drug makers are developing new medicines to treat Alzheimer’s disease.

Researcher {This is T-817MA. Researchers of this firm are studying T-817MA.}

They say it could be a new drug. This is an experiment the team carried out using animal cells. Amyloid beta protein usually kills neurons, but the team found that cells given T-817MA survive. Medical researchers have high hopes for IPS technology. It could dramatically change how new drugs are developed. To gain government approval for new drugs, pharmaceutical firms have to administer them to healthy people and confirm their safety.

But they believe using IPS cells could allow them to skip this possibly risky process. Researchers at this firm think IPS technology could enable them to more clearly determine which types of patients respond positively to new drugs. Drug makers are required to conduct clinical test to prove the effectiveness of new products. The government doesn’t approve drugs that are useful in treating only small numbers of patients. The researchers of the company and trying to identify which types of patients respond well to the new drug. To do so, they use IPS cells created with cells taken from patients and recreate the disease condition. They plan to apply for government approval for the drug which works on specific types of patients. The firms plan to put the new drugs on sales in seven years time.

Yuzo Toda, vice-president of Fujifilm {One of the purposes of our research is to categorize Alzheimer’s patients, instead of lumping them all together. I believe this is a revolutionary approach that will completely change how new drugs developed.}

Tailor-Made Medicine

Kuniya {Professor Inoue announced that his research results found there were three different types of Alzheimer’s disease. What impact will this discovery have on the development of drugs for Alzheimer’s disease?}

Yamanaka {The impact will be huge. We can take cells from 10 patients to produce IPS cells and replicate their conditions. By doing that, we can predict who will respond to a drug and who will develop side effects. This will allow us to create patient-specific drugs. We call this tailor-made medicine. Many people think tailor-made medicine is just a dream. They may think this is too expensive. But there is no need to give up on this idea. It might be difficult to produce drugs made exactly for each individual like made-to-measure cloth. But how about partly tailor-made drugs? I think IPS technology has already enabled the development of drugs that are effective in treating certain groups of patients.}

Kuniya {The government at present does not approve drugs that are effective in treating some people, but not others. As a result, many drugs end up never being used. I think the number of research team have had to abandon their studies midway.}

Yamanaka {Yes. I hope the IPS technology will help researchers complete development of new drugs. That would have been abandoned under the current approach.}

Side Effects

Kuniya {I suppose another important aspect in drug development using IPS cells is the potential in assessing toxicology.}

Yamanaka {There are cases in which drugs with no toxicity are assessed as being harmful and there are drugs with toxicity posted off as being safe. We are hoping that the use of IPS cells will reduce that kind of erroneous assessment. Most clinical trials involve 1000 people at the most. So even if a drug has no side effects in 1000 people, if it were administered to 10,000 patients, it could cause critical arrhythmia in one or two of them. In that case the drug would be banned under current regulations. But if the drug could be tested on cardiac cells created from IPS cells, we could identify patients who would suffer side effects and make sure the drug was not administered to them. If a drug works on most patients, it should be made available by clarifying who must not take it.}

Kuniya {Professor Yamanaka, you have  spoken about the various potential and benefits in drug development using IPS cells. What do you think is the key to getting pharmaceutical companies to change their way of doing business, so they are actively investing in drug development using IPS cells?}

Yamanaka {IPS cells are still very special. Scientist with experience in culturing other types of cells almost certain to fail in their attempts to culture IPS cells if they try to do it without any training. That means it will be a very long time before IPS cell technology can be used widely in drug development. I am not expecting IPS cells to bring remarkable results in the drug area. I liken them to a  runner who overtakes 10 competitors in just one section of a long relay race. Instead, I see IPS cells contributing to gradual, but steady progress in the whole process of drug development, and helping improve its success rate from 10% now to 20%. The most important thing is to make steady progress and I hope our center for IPS cell research and application can be the driving force in drug development. We will continue our efforts. We won’t give up just because results are not achieved in the short-term.}

Summary Of TV Program

Hopes are rising that IPS cells can help in the search for materials that can be used in drugs and also to confirm the safety of drugs. Not only that, using IPS cells could make it possible to identify which patients will best respond to a drug and to determine those who have side effects and those who won’t. This could pave the way for more drugs to be approved for use. Professor Yamanaka had said the use of IPS cells in drug development will not be anything remarkable. He spoke of his constant struggle to use new technology in the medical field. Professor Yamanaka also says he hopes the latest study will help more people understand the potential of IPS cells. He said he wants to work with the pharmaceutical industry and other researchers to promote the use of IPS technology.

Conclusion; where are we going from now?

A little step, but it could be a huge one for a long run. That is how I felt after watching this TV program. In the lab, the doctors and researchers have already shared a common acknowledgement that IPS cells have such a tremendous potential curing lots kind of patients. There is still a little work to do, but in the near future, we could expect that some of the incurable diseases would turn into the positive side.

Tailor-Made Medicine! Everybody will register with each personal data such as basic physical information, his or her history of illness, and his or her genetic tendency at the nearest hospital. At the hospital, the doctors collect this data and see if some unusual things had not occurred onto particular person. Data will come through the devices attaching to each person’s body like smart watches. If the doctor finds something is wrong with one human, high blood pressure or unusual body temperature, then the doctor will diagnose the symptom and send his or her home with Tailor-Made Medicine.

What if the disease would have reached already at some point where there would be no effective medicine available? In that case, we could use IPS cell technology. If the patient had an incurable stomach disease, then the doctor would decide to have spared stomach grown for that particular person. By using IPS technology, we could make our own organs and replaced them if some parts of the original ones have grown with diseases.

Then, I have a question. Are we going to die physically eventually?

In The Long Run

If the wonderful technology were available to the all the human being on the earth, that would be blessed. But that is a wish I guess. In this modern society, we have already the situation where the haves and the have nots are sharing available resources. The person with financial affordable will benefit with updated technology and the person with no financial advantage will suffer with the diseases.

What about religion? Are we happy with living for a long time forever? Can you imagine that you will live 100 or more than 150 years with healthy body? How that affects us mentally? We can accept this eternal life? What would be a mental blockage that affecting us to make choices?

We always tend to have a trend. We gain something, and then we lose something.

IPS Cell Technology


 

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