Reversing Diabetes with Reprogrammed Stem Cells – Finally a Cure?

If left untreated, diabetes can cause cardiovascular problems, as well as damage to the kidneys, eyes, nerves, hearing, and feet (including up to requiring amputation).

Untreated or poorly treated diabetes accounts for approximately 1.5 million deaths every year. And that’s despite the quality of care and drugs for diabetes to have progressed over the years.

So, it is a very impressive breakthrough that was announced by Chinese researchers that they managed to actually cure a woman suffering from type-1 diabetes.

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”.

Stem Cells To Repair The Body

Stem Cells

Most cells in our body are called differentiated cells and are specialized in their role as nerve cells, muscle cells, etc.

But they all come from so-called stem cells, which can become any type of cells during the growth of the embryos from the initial fertilized egg.

A long-standing project of biotechnology has been to produce on-demand stem cells from differentiated cells. This way, we could take abundant differentiated cells from a patient (for example skin cells) and turn them into needed heart muscle cells, liver cells, and in this example, insulin-producing islets pancreatic cells.

Source: Cell Discovery

A key advantage of this technique is that because the cells are the patient’s own, they should, in theory, not trigger immune reactions.

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.

Curing Type-1 Diabetes

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 June 2023.

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.

Source: Cell

The woman was producing naturally enough insulin after 2 and a half months, and in a self-regulating manner, that she could stop using the insulin treatment altogether. A year later, this is still true, hence the public announcement of these results.

In general, medical professionals and diabetes researchers will consider the woman “cured” if these results can hold for a total of 5 years.

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.

What About Immune Reactions?

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.

Other Islet Implant Research

Type-2 Diabetes?

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.

Universal Donor Stem Cells

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.

Source: CRISPR Therapeutics

Vertex backed out of this deal in January 2024, 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.

Other Diabetes Therapies

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.

Investing In Diabetes

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), 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”.

Diabetes Company

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 3/5^th of its employees working on R&D.

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.

Source: 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”

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).

Source: 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:

Young girls crowded into the endocrine and metabolism department of the hospital, regardless of whether they were thin or fat, just to get a dose of semaglutide.

In the doctor’s hospital, they only prescribed just over 100 doses of semaglutide in June, but now the number has risen to 1500-2000 doses, which is the average sales volume of semaglutide in most tertiary hospitals in Shanghai.

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.

“Using tirzepatide might be a lifetime decision.” Fierce Pharma – Dr. Dan Skovronsky, Eli Lilly’s chief scientific and medical officer,

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.