バイオテクノロジー
再プログラムされた幹細胞で糖尿病を逆転させる – ついに治療法が見つかるか？
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糖尿病の合併症
糖尿病は何億人もの人々に影響を及ぼす複雑な疾患です。人工インスリンなどの治療が命を救っているものの、糖尿病は依然として生活の質を低下させています。実際、糖尿病は2つの異なる病気であり、どちらも血糖値の管理不全とそれを調整するインスリンホルモンの問題が特徴です。
インスリンは血液中の糖が細胞に取り込まれることを可能にして働きます。正常に機能している場合、インスリンの産生は血糖を制御・調整します。
Classic symptoms of diabetes include weight loss, blurred vision, and what are often referred to as the “4 Ps of Diabetes”. These include,
- Polyuria (過剰な排尿)
- Polydipsia (過剰な渇き)
- Polyphagia (過剰な空腹感)
- Polyneuropathy (神経障害)
If left untreated, 糖尿病は治療されない場合、心血管系の問題や腎臓、目、神経、聴覚、足（切断が必要になることも含む）への損傷を引き起こす可能性があります.
未治療または不十分に治療された糖尿病は、毎年約150万人の死亡原因となっています。これは、糖尿病治療薬やケアの質が年々向上しているにもかかわらずです。
したがって、中国の研究者が実際に1型糖尿病の女性を治癒したと発表したことは、非常に印象的な突破口です。
The researchers from the Nankai University, China Changping Laboratory, Hangzhou Reprogenix Bioscience, and Peking University published their results in Cell under the title “Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient”.
体を修復するための幹細胞
幹細胞
Most cells in our body are called differentiated cells and are specialized in their role as nerve cells, muscle cells, etc.
しかし、これらすべては「幹細胞」から来ており、受精卵から胚が成長する過程であらゆる種類の細胞に分化できる能力を持っています。
バイオテクノロジーの長年の課題は、分化した細胞からオンデマンドで幹細胞を作り出すことです。これにより、患者から採取した豊富な分化細胞（例：皮膚細胞）を、必要な心筋細胞、肝細胞、そして本記事の例であるインスリン産生膵島細胞に変換できるようになります。
出典: Cell Discovery
この技術の大きな利点は、細胞が患者自身のものであるため、理論上は免疫反応を引き起こさないはずだという点です。
Most of the time, this has been achieved by modifying the genetics of the differentiated cells. However, a more advanced method has emerged in recent years, where subtle chemical signals are enough to reverse the normally one-way-only differentiation process.
1型糖尿病の治療
It is this method using small molecules to create stem cells from the patient’s own body the Chinese researchers used. This offered more control over the process.
The technique chemically induced pluripotent stem (iPS) cells, which were used to generate 3D clusters of islets. After years of testing the safety on mice and non-human primates, they were ready to try it on humans in 2023年6月.
They injected 1.5 million islets into the 25-year-old woman’s abdominal muscle. This differs from most previous tentative injections of pancreatic islets, usually done in the liver. The abdominal location was considered easier to monitor with MRI and also easier to remove surgically if something was going wrong.
出典: Cell
この女性は、2か月半後には自然に十分なインスリンを産生し、自己調節的にインスリン治療を完全に中止できるようになりました。1年後もこの状態は維持されており、結果の公表につながっています。
一般的に、医療専門家や糖尿病研究者は、これらの結果が5年間持続すれば「治癒」とみなすでしょう。
2 other participants in the study seem to be doing fine as well and will reach the 1-year mark in November. The plan is to expand the testing to another 10-20 people next.
免疫反応はどうか？
This test was a groundbreaking success, but some questions are still open.
An important one is that the patient was already receiving immunosuppressants for a previous liver transplant. And type-1 diabetes is caused in the first place by the body’s immune system destroying the normal healthy islets.
So this study does not clarify if the implanted islets can be used without immunosuppressants. The researchers are looking at ways to develop cells that can evade this autoimmune response.
他の膵島移植研究
2型糖尿病？
This result follows another study from 2022, also done in China by a separate group in Shanghai, titled “Treating a type 2 diabetic patient with impaired pancreatic islet function by personalized endoderm stem cell-derived islet tissue“. He, too, has since stopped needing insulin.
This shows that this strategy could be the base for a global cure for diabetes.
ユニバーサルドナー幹細胞
Vertex
While these results are impressive, the bespoke approach using one patient’s cells will be difficult to scale up to the 537 million diabetic patients in the world, a number expected to explode to 783 million by 2045.
A better alternative would be universal stem cell treatment, produced in advance and available “off the shelf”.
This is the strategy pursued by Vertex Therapeutics, which reported good results for its VX-880 experimental treatment, a stem cell-derived therapy for people with type-1 diabetes. The first patients reported needing 91% less insulin 90 days after receiving an infusion of these stem cells. And this was despite the cell injection being at first a half-dose, to be sure to be on the safe side.
VX-880 is delivered via infusion into the hepatic portal vein (liver) and requires the use of chronic immunosuppressive therapy to protect the cells from rejection or immune attack. But considering it is possible that type-1 diabetes patients might need immunosuppressants even when using their cells, this might not make much of a difference.
Vertex is also testing a medical device that would encapsulate the insulin-producing islet cells, shielding them from the patient’s immune body and the auto-immune disorder that caused the disease in the first place.
If it works, it would remove the need for immunosuppression.
It seems Vertex is rather confident about this project and its commercial future, as it is already building a dedicated manufacturing facility for the device in partnership with Lonza, with a surface of more than 130,000 square feet, and anticipated to employ 300 people at peak capacity.
CRISPR Therapeutics
The company previously partnered with Vertex to modify the genes of stem cells so that they would be able to not only turn into insulin-producing islets but also avoid the patient’s immune system.
It also relied on encapsulation and a medical device to maximize the survival of the stem cells.
Vertex backed out of this deal in 2024年1月, leaving CRISPR therapeutic to pursue the project on its own.
This might be because Vertex’s VX-880 was successful enough that they did not see an advantage anymore in partnering with CRISPR Therapeutics, a company with whom they also developed the first-ever approved gene therapy, for blood diseases.
その他の糖尿病治療法
We covered a few months ago much other progress being made in diabetes treatments in our dedicated article “Curing Diabetes With New Drugs, Smart Devices, And Gene Therapies”.
Even if stem cell therapies prove too expensive, risky, or difficult for mass adoption, there are other promising therapies like:
- Better insulin form:
- Glucose-responsive-Insulin (GRIs), for only weekly or monthly injections
- oral delivery for insulin
- Ultrastable insulin does not require keeping cold, etc.
- Better insulin devices, from glucometers integrated into smartphones to artificial pancreas.
- New diabetes drugs, which included the now more famous for anti-obesity effects GLP-1 Agonists (Wegovy), but also dozens of other molecules.
- Gene therapies, notably modifying the liver, reduce the chances of developing type-2 diabetes in the first place.
糖尿病への投資
As diabetes is moving from half a billion to three-quarters of a billion patients, it is becoming one of the major cost drivers of healthcare globally. Better medicines and medical devices are likely to be the first step in improving the therapies, with gene therapies and stem cell-based treatment maybe soon to make a difference as well.
You can invest in diabetes companies through many brokers, and you can find here, on securities.io, our recommendations for the best brokers in the USA, Canada, Australia, the UK, as well as many other countries.
If you are not interested in solely diabetes companies, you can also look into biotech ETFs like WisdomTree BioRevolution UCITS ETF (WBIO) (WT ), VanEck Biotech ETF (BBH), or First Trust NYSE Arca Biotechnology Index Fund (FBT), which will provide more diversified exposure to capitalize on the growing biotech economy.
You can also learn more by reading our articles “5 Best Stem Cell Companies to Invest In”. and “Curing Diabetes With New Drugs, Smart Devices, And Gene Therapies”.
糖尿病企業
1. Vertex Pharmaceuticals Incorporated
Vertex is a leader in treating cystic fibrosis (4 approved medicines), which is now actively diversifying in new segments. The company is very R&D focused, with 70% of its operating expenses and 3/5th of its employees working on R&D.
VRTX 価格チャート
It was working closely with one of the leaders of gene editing, CRISPR Therapeutics. They are working together on sickle cell disease therapy and beta-thalassemia.
Diabetes is by far the largest potential market for future Vertex treatment. As we have seen, Vertex is also making quick progress in developing stem cell-based diabetes therapies, both stem cells requiring immunosuppressants and medical devices not needing them.
出典: Vertex
They also have a treatment for pain in phase 3, a $4B market now dominated by opioids. Non-opioid alternatives would command premium pricing and be of interest to the medical profession at large.
Overall, Vertex is quickly making the transition from a leader in one rare disease to a massive diversified biotech company equally active in gene therapy, diabetes, and pain therapy.
2. Novo Nordisk A/S
Novo Nordisk is mostly known for its diabetes therapies, representing 79% of its current revenues. It is a company we already covered in “Top 5 Blue Chip Pharmaceutical Companies”
NVO 価格チャート
A smaller part of its activity is obesity, with just 9% of sales. But an important part is the astonishing growth rate of 84% in 2022. This is entirely based on the launch of Wegovy, an injectable weight-loss medicine. Wegovy mimics a weight-related hormone called GLP-1 (glucagon-like peptide-1).
出典: Novo Nordisk
It had a stellar start, to the point where some manufacturing issues have led to a global drug shortage. The success of Wegovy has boosted Novo Nordisk’s sales growth expectation for 2023 from 13-19% to 24-30%, as the production is now high enough to satisfy demand.
In the US, they recruited US rapper Queen Latifah for a campaign about the stigma surrounding obesity treatments. The success is global, notably in China:
若い女性たちが病院の内分泌・代謝科に殺到し、痩せているか太っているかに関わらずセマグルチドの投与を受けようとしていました。
医師の病院では、6月にセマグルチドを100回以上投与しただけでしたが、現在は1500〜2000回に増加しており、これは上海のほとんどの三次病院におけるセマグルチドの平均販売量です。
When Wegovy disappeared from inventory, the other Novo Nordisk treatment for type 2 diabetes drug Ozempic, using the same molecule, was often used as a substitute. Even Elon Musk referred to Wegovy as a way for him to lose unwanted weight.
The GLP-1-inspired drug has been a hit, even larger than Novo Nordisk expected. It might also be something that will need to be taken continuously to keep its benefit, making a long-term treatment and cash cow for Novo Nordisk.
It must nevertheless be emphasized that potential side effects are no joke, including thyroid cancer, pancreas inflammation, kidney problems, and gallstones. So it is highly recommended to get medical advice first and use it only for severe obesity, and NOT for small weight losses like the young Chinese girls mentioned above.
These issues are related to the whole metabolism, so competitors’ products will likely carry the same risks. This is something investors will want to keep in mind.
We discussed in detail the success of Wegovy in our articles “The New Blockbuster Drug: Wegovy” and what comes next in “Will Amycretin Be the Next Big Thing for Novo Nordisk?”.
When it comes to diabetes, Novo Nordisk is working on weekly and monthly insulins, better insulin pumps/implants, and DNA immunotherapy.
Novo Nordisk’s R&D pipeline also includes other diseases, notably MASH (metabolic dysfunction-associated steatohepatitis) with 4 candidate drugs.
A long-time leader in diabetes, Novo Nordisk’s history has been shaped by the improvement in diabetes therapies and the spread of the disease. It is now becoming an equally important company in treating the quickly growing obesity epidemic, with very durable and predictable cash flows from patients using its treatments.
