The world is aging fast. By 2030 the world population aged 60 years and over will be 1.4 billion, and it will grow to 2.1 billion in 2050. A larger elderly population can be disastrous to the world economy, causing healthcare costs to explode. However, if we can increase the amount of healthy productive life by even one year, it could be worth an additional US$38 trillion to the world economy.
miRscience aims to control genes to make us grow old without growing weak. They are developing new treatments using microRNAs to control genes related to muscle loss in old age.
Growing weaker
Starting around age 50, individuals begin to lose muscle mass at a rate of 1-2% annually, leading to Sarcopenia—a condition characterized by significantly reduced muscle mass.
Starting around age 50, individuals begin to lose muscle mass at a rate of 1-2% annually, leading to Sarcopenia—a condition characterized by significantly reduced muscle mass. The resulting loss in muscle power affects daily living activities such as climbing steps or even raising from a chair. The extreme loss of lean body mass present in Sarcopenia is associated with increased risk of infection, decreased immunity, and poor wound healing.
Losing muscle mass will decrease your quality of life significantly. We take too much for granted when we are young. Simple things that you don't even think about, like getting up from a chair, become challenges when you don't have enough muscles.
It is estimated that 5-13% of all people aged 60-70 are affected by Sarcopenia. These numbers increase to 11-50% for those aged 80 or above. Even for the elderly who end up not developing Sarcopenia, the yearly muscle loss can represent a big challenge to the quality of life.
To live longer, healthy, and be able to enjoy our old age, we need to solve Sarcopenia. It could be the difference between aging in bed or playing with your grandkids outside.
Gene Regulation: Beyond Destiny
The Human Genome Project was a great step forward to understanding how life works. It created a map of all human genes. In general, a gene is a biological "recipe" to "make" proteins. However, knowing all the recipes is not enough.
Imagine that you have access to all recipes from a restaurant. With this information, you know all the possible dishes that will be served at that restaurant, but you will not know at a given time what dishes are served and to whom they are served.
Each gene is a recipe, but not all recipes are being made at all times in our cellular restaurant. Not only that, but our cells are different because they are producing different recipes. Your skin cells produce a different set of recipes than your liver cells. It's like a restaurant with a chef that can cook Mexican, Italian, and Brazilian food, but the restaurant is only Italian.
Another way of seeing this is to imagine a big house with many lights. With an electrical map of all the lamps, you can tell how many are in which room. However, just by looking at the map, you can't tell which ones are activated.
The Human Genome showed us that only understanding what genes an organism has is not enough to understand how it works. Not all genes are active all the time. The dynamics of what gene is activated and when is key to understanding what's going on inside a cell.
The mechanisms of turning genes on and off are broadly called Gene Regulation. To understand how it works, first, we need to remember the "Central Dogma" of biology:
DNA -> mRNA -> Proteins
The information in the DNA is used to create mRNA ( Messenger RNA ) molecules used to build proteins. This whole process is called Gene Expression. We can say that a gene is expressed when the protein it represents is produced.
The regulation of genes can work in any of these pathway steps. One of the major ways of turning a gene off is by interfering with the mRNA being produced by it.
Think back about our house lights analogy. The light switches are the genes, the wiring between the switches and the lamps are the RNA, and the lamps are the proteins. If you cut the wires between a light switch and a lamp, the light will not turn on when you press it.
miRscience uses one of the most promising techniques to "turn off" genes called microRNA. They will use it to turn off genes related to Sarcopenia.
Finding gold in the junkyard
After the Human Genome was finished, we discovered that 99% of the human genome didn't code for any proteins. The non-coding regions were called "junk DNA" and were thought as biologically not that useful. However, inside this "junk DNA" lies the key to understanding how life works.
Inside the "junk" parts of the Genome, it was discovered a new type of DNA sequence is used to create a special kind of RNA called Micro RNA. They are essential to regulate how our genes work. The first miRNA was discovered in the early 1990s. However, miRNAs were not recognized as a distinct class of biological regulators until the early 2000s.
Micro RNAs showed that the "inactive junk" part of our DNA was one of the control centers of our cells. The miRNA ( MicroRNAs ) attaches to special proteins and becomes a molecular machine known as RISC (RNA-induced silencing complex).
The RISC machine finds and attaches to specific mRNA (messenger RNA). Remember, one step of the central dogma is that mRNA is used to make proteins; no mRNA means no protein. When RISC is attached to mRNA, the cell can't make that protein encoded in the mRNA. Since proteins are usually what "do the work" inside a cell, the gene will not have its intended effect if the protein is not made.
miRscience will create MicroRNAs to target genes related to the loss of muscle. Their "miRNA machine" will attach to the mRNA produced by those genes and stop them from being used to create proteins.
Beyond Gene Editing: Controlling Life
There is a huge market now regarding gene-editing technologies. Many genetic diseases could be fixed by editing our DNA. Those diseases were previously impossible to cure. Fixing genetic diseases by eliminating faulty genes or adding new ones has been a dream for decades, and now the first crop of treatments is getting into the market.
One example is SMA (Spinal muscular atrophy) which is a neuromuscular disease that causes muscles to become weak and waste away. People with SMA lose a specific type of nerve cell in the spinal cord (called motor neurons) that control muscle movement. In 2019 a new gene-editing treatment for SMA called Zolensma was approved by the FDA. Zolensma is the most expensive drug in the USA, costing US$ 2.5m. Zolensma is given as a one-time intravenous (IV) dose. It works by replacing the defective or missing survival motor neuron 1 (SMN1) gene.
In 2020 Jennifer Doudna won the Nobel Prize for her work with CRISPRtechnology. A discovery that gave thousands of scientists worldwide the power to edit the code of life. CRISPR presented the opportunity to edit DNA easier and cheaper than ever before.
The discovery of CRISPR led to an explosion of interest from Big Pharma and Startups to explore Gene Editing. Most of these new treatments and products are in early phase development, but the FDA approval of gene therapy treatments like Zolensma signals a promising future. Many multi-billion dollar companies will be created in the Gene Therapy space. We are only in the beginning.
Even though I'm excited about the prospect of editing human genes, I'm even more excited about controlling genes. miRscience is in its early days of using Micro RNA to control Gene Expression. The applications of its technology can go much further than Sarcopenia treatments. The more we understand how our cells work, the more it will be clear that Gene Regulation is the key to controlling cell behavior.
Life is made of a complex network of chemical reactions. Removing and adding Genes is a powerful first step, but it's a limited form of control. It's like turning off light by removing the light bulb instead of just turning a switch on and off. I believe that the most complex biological behavior is a function of the genes and the control system of those genes. We will not fully understand how life works if we don't take control of the switches.
Amazing. Now , the big question is : which companies are the mostly likely to be successful on this technology ? Please keep in mind your answer will not be treated as an investing recommendation (maybe it will) .....just kidding , it will not. Cheers
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