If our mouse experiments have shown that a candidate drug is safe and effective, it is time to move on to the final stage: clinical trials!
Ultimately, the clinical trials will tell us whether people get the same benefits from the treatment as the mice did. These trials are very heavily monitored and regulated by the government to ensure that researchers gain the most information while ensuring the safety of the people participating in the research.
Clinical trials have multiple phases, including phases to determine dosages, efficacy, and side effects of the treatment. These trials frequently last several years and involve children and adults with the condition we are working to treat.
Once a treatment has made it through the clinical trials and has been approved by the FDA, it is finally available for treatment!
Thursday, May 31, 2012
Thursday, May 24, 2012
Step 8: Animal Models
Once we have identified a treatment that seems to work in test tubes and petri dishes, it is time to see whether it works in living things. The most common animal used in these types of experiments is the mouse. We would use a mouse that has been specifically genetically engineered to have a missing or extra copy of the gene that we were evaluating in the lab. These mice would have similar medical problems to the ones seen in individuals missing that particular gene. The mice experiments will tell us many things.
First, we want to know whether this treatment is effective in a living organism. Experiments in a test tube can be rigidly controlled. We can control which reactions go on inside the test tube. We can also control the amount of different substances and proteins we put into the experiment. However, a living organism is much more complex, and no test tube experiment can fully replicate the full range of reactions and variables that are present in an animal. We want to know whether, in the complex environment of a living organism, the drug either reduce or enhance gene expression.
Another goal of these experiments will be to see whether the drug actually makes the problems better. Does compensation for the extra or missing gene actually cure the problem, or, at the very least, improve it? For example, if we know that a gene is linked to dysmyelination, does treatment with this drug candidate improve myelination in these mice?
Third, we want to get an idea about the potential side effects of this drug in living organisms. If the drug successfully treats the underlying problem but the side effects are worse than the original problem, it is probably not a good drug candidate.
Once we have determined that a particular drug is effective and safe in mice, we can move on to the next stage: clinical trials!
First, we want to know whether this treatment is effective in a living organism. Experiments in a test tube can be rigidly controlled. We can control which reactions go on inside the test tube. We can also control the amount of different substances and proteins we put into the experiment. However, a living organism is much more complex, and no test tube experiment can fully replicate the full range of reactions and variables that are present in an animal. We want to know whether, in the complex environment of a living organism, the drug either reduce or enhance gene expression.
Another goal of these experiments will be to see whether the drug actually makes the problems better. Does compensation for the extra or missing gene actually cure the problem, or, at the very least, improve it? For example, if we know that a gene is linked to dysmyelination, does treatment with this drug candidate improve myelination in these mice?
Third, we want to get an idea about the potential side effects of this drug in living organisms. If the drug successfully treats the underlying problem but the side effects are worse than the original problem, it is probably not a good drug candidate.
Once we have determined that a particular drug is effective and safe in mice, we can move on to the next stage: clinical trials!
Thursday, May 17, 2012
Step 7: Treatment Development
This step marks the beginning of our ultimate goal: the development of a treatment for chromosome 18 conditions! Up to this point, we have…
1. Learned all that has already been written about the condition (Literature Review)
2. Fully investigated individuals with these conditions, both from a clinical and a molecular standpoint (Clinical and Molecular Assessments)
3. Fully described the various medical and developmental concerns associated with the condition (Syndrome Description)
4. Identified the genes directly responsible for the various features of the condition (Gene Identification)
5. Created personalized management plans based on the genes involved (Syndrome Management Plan)
6. Figured out how a change in the number of genes leads to the features of the condition. (Gene Function Studies)
We’ve come a long way from where we started, when precious little was known about each of these conditions. At this point of the path, we will be able to predict which children are likely to have which complication, and we will be able to make up a plan specific to that person’s genetic situation.
Of course, there is still much work to be done. We still want to develop a treatment that addresses the root cause of the issue: the deletion or duplication. We are looking for a molecular “fix”, so to speak.
To do this, we must look for treatments that “make up” for the missing or extra pieces of chromosome. In order to understand how we approach this challenge, it is important to have a basic understanding of genetic concepts. Humans have two copies of each chromosome. Genes are located on the chromosomes. These genes code for proteins that play different roles throughout the body. There are proteins that carry oxygen, proteins that help digest food; proteins that tell our body when to start producing certain hormones, and more! Proteins play an important role in all of the body’s functions.
So, what happens when there are missing or extra copies of a gene? There may be too little or too much of the protein that the gene codes for. This is likely the mechanism by which missing or extra copies of a gene lead to the various concerns associated with chromosome 18 conditions. So, we want to find drugs that will either (1) increase the expression of a gene in a person with a deletion or (2) decrease the expression of a gene in a person with a duplication.
We start our search for a treatment in the laboratory. We look at the effects of different drugs on gene expression. At this point, we are just looking at the effects of the drug in vitro. This means that we are looking at how the drug works outside of a living organism (for example, in test tubes or petri dishes). When we find one that seems to affect gene expression, we have found a potential treatment! It is then time to move on to our next step: Animal Models!
1. Learned all that has already been written about the condition (Literature Review)
2. Fully investigated individuals with these conditions, both from a clinical and a molecular standpoint (Clinical and Molecular Assessments)
3. Fully described the various medical and developmental concerns associated with the condition (Syndrome Description)
4. Identified the genes directly responsible for the various features of the condition (Gene Identification)
5. Created personalized management plans based on the genes involved (Syndrome Management Plan)
6. Figured out how a change in the number of genes leads to the features of the condition. (Gene Function Studies)
We’ve come a long way from where we started, when precious little was known about each of these conditions. At this point of the path, we will be able to predict which children are likely to have which complication, and we will be able to make up a plan specific to that person’s genetic situation.
Of course, there is still much work to be done. We still want to develop a treatment that addresses the root cause of the issue: the deletion or duplication. We are looking for a molecular “fix”, so to speak.
To do this, we must look for treatments that “make up” for the missing or extra pieces of chromosome. In order to understand how we approach this challenge, it is important to have a basic understanding of genetic concepts. Humans have two copies of each chromosome. Genes are located on the chromosomes. These genes code for proteins that play different roles throughout the body. There are proteins that carry oxygen, proteins that help digest food; proteins that tell our body when to start producing certain hormones, and more! Proteins play an important role in all of the body’s functions.
So, what happens when there are missing or extra copies of a gene? There may be too little or too much of the protein that the gene codes for. This is likely the mechanism by which missing or extra copies of a gene lead to the various concerns associated with chromosome 18 conditions. So, we want to find drugs that will either (1) increase the expression of a gene in a person with a deletion or (2) decrease the expression of a gene in a person with a duplication.
We start our search for a treatment in the laboratory. We look at the effects of different drugs on gene expression. At this point, we are just looking at the effects of the drug in vitro. This means that we are looking at how the drug works outside of a living organism (for example, in test tubes or petri dishes). When we find one that seems to affect gene expression, we have found a potential treatment! It is then time to move on to our next step: Animal Models!
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