Before continuing reading, we strongly advise you to first read about the GRIN Disorders
Many of you probably asked your doctor what can be done, and heard that there is no drug and no way to correct a genetic mutation.
This was true 6 years ago. This is not true today. Six years ago, a revolution occurred in the field of genetics. Scientists today can correct genetic mutation in a very efficient and straightforward way. All thanks to incredible genetic revelations.
Our vision: Find a cure for GRIN Disorders
Our strategy: Access to a wide variety of treatment options
Short term: Drug therapy
Long term: Gene therapy
Creating brain cells from each child (or adult) with a GRIN disorder. We create a cell bank from each person’s skin or blood cells through a minimally invasive procedure.
The cells grow in the lab and produce an endless reservoir for any future requests. Since GRIN genes are expressed in the brain, we will create neurons and use them to test drugs or specific personalized gene therapies uniquely designed for any individual variant/patient.
Animal models for testing the various treatments
Creating animals with human mutations to test both drug and gene therapies before performing clinical trials on humans. Safety is a major issue, therefore we need to test treatments, even if they are considered to be safe.
Using high throughput automatic screening (executed by a robot) of several thousands of FDA-approved drugs, natural compounds and more. If successful, they can be given without further testing to the children.
Using computational tools to design and screen millions of compounds, with the drawback of having to test for toxicities and side effects prior to use.
Gene therapy (Gene editing)
In gene editing, we can target the root of the problem. The long-term goal, to find the single procedure with a definitive cure – gene editing. GRIN disorder is caused by a mutation in only one of the two copies of the gene. The plan is to shut down the faulty copy, while preserving the good copy. The approach is personalized: As a whole, the procedure is the same for all mutations, with the exception of design. Every mutation’s design will be different.
Once Gene Editing works on human cells (in a laboratory), we will test it on animals, and then continue with clinical testing in humans.
What is gene editing?
It is equivalent to finding and replacing features used to correct misspellings in documents written on a computer. Gene editing rewrites DNA, the biological code that makes up the instruction manuals of living organisms. With gene editing, researchers can disable target genes, correct harmful mutations, and change the activity of specific genes including humans.
Much of the excitement around gene editing is fueled by its potential to treat or prevent human diseases. They are not rare: One in 25 children is born with a genetic disease. Among the most common are cystic fibrosis, sickle cell anemia and muscular dystrophy. Gene editing holds the promise of treating these disorders by rewriting the corrupt DNA in patients’ cells. But it can do far more than mend faulty genes.
How does it work?
The molecular tool is called CRISPR-Cas9. It uses a guide molecule (the CRISPR bit) to find a specific region in an organism’s genetic code – a mutated gene, for example – which is then cut by an enzyme (Cas9) and effectively disables the gene. This is useful for turning off harmful genes, but other kinds of repairs are possible. For example, to mend a faulty gene, scientists can cut the mutated DNA and replace it with a healthy strand that is injected alongside the CRISPR-Cas9 molecules. Different enzymes can be used instead of Cas9, such as Cpf1, which may help edit DNA more effectively.
How do you get to the right cells?
Most drugs are small molecules that can be ferried around the body in the bloodstream and delivered to organs and tissues on the way. The gene editing molecules are big and have trouble getting into cells, but it can be done. One way is to pack the gene editing molecules into harmless viruses that infect particular types of cell. Millions of these are then injected into the bloodstream or directly into affected tissues. Once in the body, the viruses invade the target cells and release the gene editing molecules to do their work. In 2017, scientists used this approach to treat Duchenne muscular dystrophy in mice. The next step is a clinical trial in humans. Viruses are not the only way to do this. Researchers have used fatty nanoparticles to carry CRISPR-Cas9 molecules to the liver, and tiny zaps of electricity to open pores in embryos through which gene editing molecules can enter.
We have a specially designed guide RNA that will lead CRISPR to the mutation, cut the faulty DNA and abolish it. On a different approach, we are doing a BE not GE, meaning that we don’t cut the DNA. Instead it is nicked, which changes the nucleotide to the original one.
A gentler form of gene editing that doesn’t cut DNA into pieces, but instead uses chemical reactions to change the letters of the genetic code. It is more precise and with fewer side effects. In 2017, researchers in China used base editing to mend mutations that cause a serious anemia in human embryos.
Sometimes you don’t want to completely remove or replace a gene, but simply reduce or increase its activity. This is suitable to deletions when you don’t have enough of your normal GRIN gene and you want to increase its amount.
Why gene therapy?
We believe this is the preferred method for us because it allows us to change a single nucleotide. Since it doesn’t cut the DNA, it is potentially very safe. The problem is that right now we can cut every gene we want with CRISPR, however this base editing is available to some but not all mutations. For instance, it can change A to G and vise versa. So if the GRIN is caused by a G to A, it can change it back. But for G to T, there is currently no enzyme. Nowadays, many laboratories worldwide search for enzymes for the changes yet to be available.
How long before it’s ready for patients?
The race is on to get gene editing therapies into the clinic. A dozen or so CRISPR-Cas9 trials are underway or planned. One of the first launched in 2016, when doctors in Sichuan province gave edited immune cells to a patient with advanced lung cancer. Gene editing has already been used to modify people’s immune cells to fight cancer or be resistant to HIV infection. More US and European trials are expected in the next few years.