When I first encountered the article about the potential to grow new teeth, my initial reaction was, "Count me in; I want to try it." It filled me with hope. The idea of not having to resort to artificial teeth, despite their necessity, is thrilling because teeth are so crucial to our health.

I haven't shared this I belive until today, but I was raised by my aunt and uncle when I was on the first grade of school so roughly 5-6 years old. My aunt, being a dentist, meant I spent a lot of time at her clinic. I became familiar with the daily routines, greeting patients, and learning about their dental issues. I even watched my uncle prepare mercury fillings, which I found fascinating at the time. At the end I would know the exact process to be done, I would often assist and knew what spatula would be needed. Now that I think of it, I don’t know why I never became a dentist, but that is a tale for another time. It seemed like everyone in Albania had these fillings back then, and many probably still do today. Growing up in this environment instilled in me a sense of resilience and comfort with dental care, eliminating any typical fear of dentists or doctors.

However, 25 years ago, dentistry wasn't as advanced. Tooth extraction was often the primary solution instead of preservation. It's disheartening to reflect on the limited options available then. Now, in 2024, I'm genuinely excited to witness this era of medical and dental progress. Advancements like tooth regeneration offer a beacon of hope for dental health, transforming lives in ways I couldn't have imagined during my childhood.

A Japanese research team has potentially developed the world's first medicine for tooth regrowth. The team, led by Katsu Takahashi from the Medical Research Institute Kitano Hospital in Osaka, published their groundbreaking research in Science Journal in 2021. The drug targets individuals with congenital anodontia, a condition characterized by the absence of some or all permanent teeth. Takahashi's interest in tooth regeneration dates back to his graduate student days. A significant breakthrough occurred around 2005 during his research at Kyoto University. The team discovered that mice lacking a specific gene developed extra teeth due to a protein called USAG-1. In normal circumstances, USAG-1 limits tooth growth.

So now you would think what is USAG-1? By the way ‘usagi’ in Japanese means rabbit, so just a fun note here.

What is USAG-1?
USAG-1 is a protein in our body that usually stops too many teeth from growing. It does this by blocking signals called Bone Morphogenetic Proteins (BMP) that tell teeth to grow. Meaning that if there's not enough USAG-1, these growth signals (BMP) can work freely, which can lead to extra teeth growing. This is because USAG-1 normally works to balance out these signals.

So the research team found this and thought to make special antibodies that can stop USAG-1 from blocking these growth signals. But these antibodies are very specific; they only stop USAG-1 from interfering with BMP signals, not with other signals like Lipoprotein Receptor-related Protein 5/6 (LRP5/6).

Now why this is important is because USAG-1 usually keeps tooth growth in check, when you block its function, either by removing the gene (knockout) or using these antibodies, it allows teeth to grow where they normally wouldn't or when they normally wouldn't.

The Animal Experiment: The drug was successfully tested on mice in 2018, where it induced the growth of third-generation teeth. In mice that naturally have fewer teeth due to genetic issues, blocking USAG-1 with these methods led to more teeth growing. This means USAG-1 is like a brake on tooth growth, and by removing this brake, teeth can develop. Further experiments on ferrets, which have dental patterns similar to humans, also showed positive results, growing an additional tooth without adverse effects.

So the idea here is that if you can control USAG-1 in humans, you might be able to help people who are born with too few teeth or as called congenital tooth agenesis grow more teeth naturally.( It refers to a condition where an individual is born with an absence of one or more teeth.)

Humans typically have two sets of teeth: baby teeth first, which fall out to be replaced by adult teeth, except for the wisdom teeth. However, occasionally, people can develop additional small or rudimentary teeth beyond their regular adult set. Researchers, after studying 78 individuals with these extra teeth, suggested that this phenomenon might be due to the activation of what could be considered a "third set" of teeth. They propose that by understanding and activating this process with targeted treatments, it might be possible to help people regenerate new teeth if they are missing some.

The team is preparing for clinical trials, started in September 2024, to confirm the drug's safety in humans. Initially, these trials will involve healthy adults missing teeth, with plans to later include children aged 2 to 6 with congenital anodontia. If successful, the drug could be available for general use by around 2030, offering a new option for tooth loss due to congenital conditions, cavities, or other reasons, potentially reducing reliance on dentures or implants.

Katsu Takahashi expressed hope that this treatment could become a "third choice" alongside traditional treatments like dentures and implants, significantly impacting dental care. This development marks a significant advancement in dental science, promising a future where tooth loss might not be permanent, especially for those affected by genetic conditions preventing natural tooth growth.

References:

1. Science Advances. "Advancements in regenerative medicine for dental applications." https://www.science.org/doi/10.1126/sciadv.abf1798.

2. Kyoto University. "Breakthrough research on regenerative dental medicine." (March 31, 2021). https://www.kyoto-u.ac.jp/en/research-news/2021-03-31.

3. Kyoto University. "Development of innovative dental therapies using stem cells." (February 15, 2021). https://www.kyoto-u.ac.jp/ja/research-news/2021-02-15-0.

4. Nature Scientific Reports. "A novel approach to dental tissue regeneration." Scientific Reports 11, Article number: 93256 (2021). https://www.nature.com/articles/s41598-021-93256-y.

5. Toregem Biopharma. "Development of groundbreaking projects in dental medicine." https://toregem.co.jp/en/development-project-2.

6. JStories Media. "The world’s first drug to help patients grow new teeth." Update article. https://jstories.media/article/the-worlds-first-drug-that-helps-patients-grow-new-teeth-update.