Challenge to develop a novel therapeutic drug for muscular dystrophy!
Reached the funding target!
Crowdfunding, which supports the "animal testing of new therapeutic molecules for muscle dysfunction" being conducted by Academist Co., Ltd., has greatly helped many people. February 15, 2021 (Monday) before 6:00 pm, the total amount of donations exceeded the initial target of 1 million yen. Thank you very much for your help. The first target amount was achieved in 12 days and 7 hours 47 minutes. This is a very fast pace. This was made possible by the supporters' deep understanding of the importance of our animal testing of Duchenne muscular dystrophy. I'm really happy about that. We could clear the first goal of 1 million yen, but this was the minimum amount of money needed to acquire the minimum amount of in vivo data. We set a second goal because we thought that we would not be able to obtain accurate animal test data unless we could perform pharmacological experiments using a sufficient number of muscular dystrophy mice. Ultimately, we aim to cover the total cost of the experiment. The animal testing that sets the final target amount to around 2 million yen, we gradually achieve the latest goals step by step, and reveals a wider and more accurate pharmacological action spectrum of the therapeutic molecule in the animal body by expanding the funding. We appreciate your understanding and cooperation. First of all, I would like to express my deep gratitude for your donating the initial target of 1 million yen. Thank you for your continued support and cooperation.
2nd goal: 1.25 million yen (1 million yen) For covering the reagent fee with increased usage
3rd goal: 1.53 million yen (1.22 million yen) For covering the cost of the mice in the animal testing
4th goal: 1.7 million yen (1.36 million yen) For covering the cost of mass synthesis of drugs
5th goal: 1.97 million yen (1.58 million yen) For covering the labor cost of increased work time
◆ The amount in parentheses is the amount after deducting the commission that can actually be used for the experiment.
Experiments will be conducted with 6 muscular dystrophic mice (genetically modified Mdx52 mice).
In addition, one non-administered control mouse (control mouse of the same strain)
◆We'll use control mice that have the same genetic background as the genetically modified Mdx52 mice.
A total of 7 mice are used. We'll purchase all of these from RIKEN BRC in Tsukuba city. RIKEN BRC mice cost ¥ 30,800 each.
Therefore, 7 animals × ¥ 30,800 = ¥ 215,600. Tax ¥ 21,560 is charged on this. Total of ¥ 237,160 --- A
In addition to this, inspection fee for quality control is required separately, and a RIKEN BRC standard inspection fee of ¥ 37,400 will be charged for each animal.
7 animals × ¥ 37,400 = ¥ 261,800. Tax ¥ 26,180 is charged on this.
Total _ ¥ 287,980 --- B
Therefore, total all cost in purchasing mice (A + B) _ ¥ 525,140 is required.
Comment from academist staff
Aiming to realize a more active and social life for patients
academist Shimojo
Limitations of current Duchenne muscular dystrophy treatment
Do you know the disease called “muscular dystrophy”? Muscular dystrophy is an intractable disease that causes various disorders in the muscle function in the body due to mutations in genes. This disease is also a rare and intractable disease that is said to occur in several to dozens of people per 100,000 population.
There are various types of muscular dystrophy, and one of them, Duchenne Muscular Dystrophy (DMD), occurs when a protein called "dystrophin" that supports muscle cells cannot be produced normally due to a mutation in the dystrophin gene. As dystrophin gradually disappears from muscle cells and muscles throughout the body are lost, the patient becomes unable to walk independently and has difficulty breathing spontaneously. Besides, the heart is also made up of muscles, so people often die of heart failure.
The dystrophin gene in DMD patients is missing a part of "exon", which is a region that has information for synthesizing proteins. In a genetic information system, three base-pair sequences are used as a reading unit (codon) to synthesize messenger RNA (mRNA) into protein (= translation), but in DMD, dystrophin genetic information’s translation is lost due to deleted exon sequence, which is not a multiple of three. Therefore, Translation by each codon in dystrophin mRNA is disturbed. As a result, translation stops in the middle, and normal dystrophin synthesis is not completed eventually.
Current DMD medications correct the deviation of the reading frame of this dystrophin gene sequence by "skipping other normal exons" so that the genetic information of dystrophin can be read to the end. However, because the skipped normal exon’s genetic information is not synthesized into proteins, dystrophins are shorter than normal and have poor performance. Therefore, even if the drug can produce the minimum amount of dystrophin necessary for survival, it will be difficult to recover to a life where the DMD patients can walk independently.
A new therapeutic molecule that enables translate to maximum length dystrophin
In an experiment using a cell-free protein synthesis system that was just developed in the laboratory I belonged to in the doctoral program at the University of Tokyo, I succeeded to synthesize intentionally shifted protein at the part where genetic information is translated to synthesize proteins. In this basic research, I have developed to design a novel molecule that can synthesize genes such as dystrophin, which cannot be translated normally due to gene mutation, into the maximum length protein without skipping the genetic information of normal exons.
I launched a biotech company in 2016 to commercialize such a new therapeutic molecule and have been conducting research. In March 2020, I completed the patent application for this therapeutic molecule to the Japan Patent Office (Japanese Patent Application No. 2020-41637).
So far, the effects of this therapeutic molecule have been investigated in experiments using DMD patient-derived cells, and the results suggest that the normal translation of the dystrophin gene has been restored. The next goal of the experiment is to clarify the effectiveness of this therapeutic molecule at an " individual level" rather than at a "cellular level".
To confirm the effect of the new drug in an animal test using mice
In cell-level experiments, therapeutic molecules can be transfected directly to cells, but “at an animal individual level” experiments, the effect must be confirmed by intravenous injection. The therapeutic molecule administered to the blood needs to enter the bloodstream to reach the target muscle cells, such as skeletal muscles and myocardium, permeate the cell membrane, and enter the cells safely. During that time, if the therapeutic molecule must not be degraded by enzymes in the blood or bound to other proteins and must not lose its effectiveness.
Therefore, in this animal test, a special drug delivery system (DDS) is employed to maintain the stability of the therapeutic molecule in the body until it reaches the target muscle cell. The system has already been used in clinical trials for other diseases, allowing testing in mice under conditions closer to clinical application in humans.
Using the DDS, it is investigated whether dystrophin is expressed in the fibers of muscle tissues such as skeletal muscle and heart in DMD mice systematically administrated by the therapeutic molecule, and the effectiveness of the therapeutic molecule is statistically analyzed. If the test gives a positive result, I’m planning to measure the efficacy of DMD mice on motor function.
Calling for your research funding support
In this experiment, I aim to obtain even a little positive result in the development of the new therapeutic drug and move the project forward, leading to the next development step. In the future, further animal tests will be required to measure the dose, toxicity, and lethal dose of therapeutic agents in detail, and subsequently animal tests using large mammals are required. It is currently difficult for a private drug discovery venture company that has just launched to procure research funds for drug development of rare intractable diseases, therefore I hope this crowdfunding becomes a "priming" for raising funds necessary for future development.
Furthermore, through this crowdfunding, I hope this activity can change the social consciousness surrounding intractable diseases by letting many people know about the rare intractable disease called muscular dystrophy and we can promote the research activity in the development of new therapeutic agents with the participation of the general public. I hope that more people are able to pay attention to intractable disease patients as much as possible and participate in this activity to make this therapeutic drug.
It is a very small wish if I would make a great effort to create a new drug for a very rare intractable disease. However, because of the small number of DMD patients, there are certainly patients in this society who are suffering without a cure and are suffering without our knowledge. If our new drug can really emancipate patients from the world of agony, inconvenience, and patience, it will pay off a great deal of effort and save us at the same time. Your support will be a great help to us. Thank you very much for your understanding and help.
Profile
Takamitsu Yano
I’m developing new drugs targeting so-called intractable diseases. This is not research and development of drugs for diseases that are at risk for anyone, such as cancer and lifestyle-related diseases, but for diseases that have a very rare incidence of a few people per 100,000 population. The reason for this goes back to my research in the doctoral program at the University of Tokyo, where I did basic research on intractable diseases of rare muscle diseases. It may also be due to the fact that I was studying at the Medical Genetics Laboratory, which was studying various human genetic diseases in the master's program at the University of Tsukuba in Japan.
At that time, I had never actually met a patient with the disease, and every day I was just imagining the patient in the lab, but afterward, I went to the States and worked at the University of California, San Diego, and I had the opportunity to meet real patients (who were children) at the university medical center. I was a basic researcher from a biological field and I was not a clinical doctor who knew the situation surrounding the patients well, so it was the first time to actually meet patients with the intractable disease and get to know their conditions. In the laboratory, I was engaged in many experiments, culturing and analyzing gene mutations in patient’s cells, but I was really shocked by how terrible and miserable their symptoms were when I first met the patients and I shed tears at the children.
After returning to Japan, I retired from my university and started a company in 2016 to pharmaceutical the therapeutic molecules that may be the new drugs I found. The company's business and research and development (R & D) are progressing, albeit little by little, with the support of various people. Anyway, with the aim of creating one new drug, many people from various fields are involved, holding hands, discussing, and proceeding with the project, regardless of people in humanities or sciences. Every day, I find myself in a world that would be unthinkable for a researcher belonging to a university.
Project timeline
| Date | Plans |
|---|---|
| February 2021 | Launch of the crowdfunding project |
| February 2021～ | Preparation for the animal test |
| May 2021 | Launch of the animal test |
| July 2021 | Analysis of the animal test data |
| September 2021 | Publication of the patent application |
| December 2021 | Presentation at an academic conference/Release a research report |
Pledge Rewards
I will summarize the results of the first animal test in a report and send it as a PDF file around January 2022.
Research Report
11 supporters are supporting with this reward. （No quantity limit）
Your name will be listed on the research report as a funder.
Acknowledgement in the research report / Research report
19 supporters are supporting with this reward. （No quantity limit）
I invite you to an online science cafe. I would like to discuss with you new treatments for incurable neuromuscular disease. The event is scheduled to be held at 8:00 pm - 10:30 pm (PST) on Saturday November 6th in 2021.
Online science cafe / Acknowledgement in the research report / Research report
7 supporters are supporting with this reward. （No quantity limit）
I invite you to an online seminar on the mechanism of abnormal gene expression and genetic diseases. The event is scheduled to be held at 9:00 pm - 11:30 pm (PST) on Friday November 19th in 2021.
Online seminar / Online science cafe / Acknowledgement in the research report / Research report
2 supporters are supporting with this reward. （No quantity limit）
Your name will be listed and acknowledged as a funder when I publish the outcome of this project in an academic paper.
Acknowledgement in an academic paper / Online seminar / Online science cafe / Acknowledgement in the research report / Research report
3 supporters are supporting with this reward. （No quantity limit）
I invite you to a one-on-one, individual discussion on DMD cell and the animal testing. I can also talk about the latest topics, etc., according to your needs. The event is scheduled to be held around September 2021.
Individual discussion / Acknowledgement in an academic paper / Online seminar / Online science cafe / Acknowledgement in the research report / Research report
8 supporters are supporting with this reward. （No quantity limit）
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Research Report
11
supporters
back
（No quantity limit）
Acknowledgement in the research report and others
19
supporters
back
（No quantity limit）
Online science cafe and others
7
supporters
back
（No quantity limit）
Online seminar and others
2
supporters
back
（No quantity limit）
Acknowledgement in an academic paper and others
3
supporters
back
（No quantity limit）
Individual discussion and others
8
supporters
back
（No quantity limit）
academist Prize 3rd adopted
