Genetic Treatments for Acne

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Genetic Treatments for Acne May Be a Real Possibility in the Future, but None Exist Today, and None Are Currently in Development

• How Gene Therapy Works
• What Diseases Are Candidates for Genetic Treatment?
• How Safe Is Gene Therapy?
• Is Gene Therapy Ethical?
• The Bottom Line

Gene therapy is a relatively new type of treatment that adds or replaces genes to treat or prevent diseases. The idea is to either fix defective genes that cause a disease or to replace them with healthy genes.¹ Gene therapy is currently available for a handful of diseases and is undergoing testing for many others. In most cases, these are serious diseases that have no other cure.^2,3

At this point, no gene therapy is available for acne, nor are any clinical trials underway to test future gene therapy treatments for acne. For such treatments to become a reality, scientists will need to overcome several hurdles:

1. Identify genes that contribute to acne: Gene therapy can only work on diseases that have a genetic component. In other words, it is only effective for diseases that result, at least in part, from a defective gene. Scientists believe that acne is such a disease. One gene that might be defective in people with acne is called FoxO1. Normally, FoxO1 acts like a volume control button, suppressing other genes that contribute to key steps in acne development: the overproduction of skin oil, the overgrowth of skin cells, and inflammation. Scientists think that in people with acne, the FoxO1 gene might be underperforming. Another reason to suspect FoxO1 of being faulty in acne is that some acne treatments, like the topical retinoid adapalene, actually work by boosting the activity of FoxO1.⁴ Of course, it is likely that acne is a polygenic disease, which means that many different genes, if they malfunction, probably increase the likelihood of a person developing acne. This means that we need to identify all the genes that contribute to acne before we can develop a genetic treatment for it.^5-7
2. Develop techniques to fix/replace multiple genes simultaneously: Since acne is likely a polygenic disease, for gene therapy to work, scientists would have to find a way to fix multiple genes at the same time. So far, the genetic treatments that have been successful have only had to fix or replace a single defective gene. This means that technical advances are necessary before we can attempt to treat acne genetically.
3. Find a way to target only skin cells: One of the main challenges in gene therapy today is how to target only the cells that play a role in a disease. For acne, this means targeting only skin cells and not, say, heart muscle or brain cells. Changing the genes in the wrong cells could result in serious side effects. This means scientists must find a way to zero in on just skin cells for gene therapy to be a safe option for acne.
4. Thoroughly test any new genetic acne treatment: Changing a person’s genes can lead to unpredictable health risks. This is why any new genetic treatment must undergo rigorous testing and receive approval from regulatory agencies before doctors can prescribe it.¹ This process can take over a decade. This means in a best case scenario we are still many years away from a genetic acne treatment being available to patients.

Even if scientists overcome all these hurdles, acne is still a so-called multifactorial disease.⁵ This means that many other factors besides genes combine to cause acne. In other words, gene therapy may help with acne but probably not cure it.

Still, there is reason to be optimistic. Cancer is another multifactorial disease involving many genes and many research groups are already testing experimental genetic treatments for cancer. One day, genetic treatment for acne may be a real possibility as well.

How Gene Therapy Works

To understand how gene therapy works, we first need to remind ourselves what genes are.

What is a gene and where does it live?

A gene is a piece of DNA containing instructions for making a protein. Proteins are the building blocks of our bodies. In other words, genes are the recipes our cells use to build and repair our bodies.

Genes come in different lengths, but all human genes live in one place in the cell: the nucleus (an organelle in the center of the cell). The nucleus of each cell contains DNA coiled into rope-like structures called chromosomes. Each chromosome is the home of hundreds or even thousands of genes.²

The Human Genome Project, an international research program that began in 1990, concluded that each human cell contains between 22,000 and 25,000 genes.²

Scientists name each gene using a combination of letters and sometimes numbers according to its function. For example, the KRT1 gene provides the recipe for our skin cells to make a protein called keratin-1.⁸

How genes can go wrong

Genes can go wrong in three ways:

1. A gene may be missing from birth
2. A gene may be defective from birth
3. A gene may mutate (change) during a person’s life

Depending on the gene, some abnormalities may be harmless, but some can disrupt the production of important proteins and lead to diseases.

The goal of genetic treatment

The aim of genetic treatment is to add missing genes or to fix abnormal genes that underlie a disease. Ideally, this should restore the body’s ability to make key proteins so that the body functions correctly and becomes healthy again.

How is it done?

Now let’s get into the deeper science of how we fix or replace genes when those genes are inside the cells of a fully-grown person. There are two ways to do it: gene therapy or gene editing.

1. Gene Therapy (introducing new genes)

The idea of gene therapy is to introduce new, functioning genes to compensate for the ones that are defective or missing in the body. In other words, instead of attempting to fix the existing “bad” genes in the person’s body, we just add “good” ones.

This sounds simple but is a technical challenge. The problem is that we cannot just inject the correct genes into the body. We need to somehow get them into the nucleus of the cells. To do that, scientists use something called a vector (a sort of carrier or delivery system). The simplest vector is a virus, because viruses are naturally good at getting into people’s cells and entering the nucleus. Of course, to use a virus as a vector, scientists have to tinker with it first so that it cannot cause illness–otherwise, the cure might be worse than the disease!^1,2

Gene therapy is currently available for a handful of diseases and is being tested on patients for many others. Acne is not among these diseases. However, just recently, researchers reported on a successful gene therapy treatment of two people with a different, severe skin disease called epidermolysis bullosa.

2. Gene editing (repairing an existing gene)

The idea of gene editing is to repair the defective genes in the person’s body. In other words, instead of adding “good” genes, we try to fix the existing “bad” ones so they will function correctly.

Gene editing is very tricky because it requires a way of getting into the nucleus of cells, finding the malfunctioning genes among tens of thousands of other genes, and then making precise changes to just those genes–all of this in a living, breathing person. Currently, scientists use specialized molecules that work like scissors, cutting DNA at very specific places.

Compared to gene therapy, gene editing is still in its infancy. However, researchers from the U.S. have successfully used this method to correct the mutation of the hemoglobin gene that causes sickle cell anemia.¹ Many clinical trials (large studies on patients) are testing gene editing for various diseases.

In other words, this is a rapidly developing and promising area of research. Still, gene editing is risky: accidentally editing the wrong genes could spell disaster, which is why extensive testing is necessary before gene editing becomes widely available.

What Diseases Are Candidates for Genetic Treatment?

In theory, any disease with a genetic component is a potential candidate for genetic treatment. Acne qualifies, because a family history of acne makes a person more likely to develop the disease.

However, developing, testing, and obtaining government approval for a new genetic treatment is a massive undertaking. As a first priority, scientists are focusing their research efforts on diseases that:

• Are very serious
• Have no other cure
• Result from a problem with a single gene^1,2

Acne does not fit these criteria because it is not life-threatening, can improve with existing treatments, and most likely results from many factors, including multiple genes. Therefore, right now no genetic treatments for acne are available or are even far enough in development to be tested on patients.

Diseases currently treated with gene therapy

However, in recent years, many more gene therapy treatments have been approved for life-threatening diseases by medical regulatory bodies in Europe and the U.S.^13,14

Diseases for which genetic treatments are currently being tested

In addition, clinical trials (large studies testing gene therapy on patients) are underway for many other diseases.^15-18 The vast majority of these clinical trials (over 60%) are taking place in the United States.³

The table below shows the disorders for which regulatory agencies have approved clinical trials.³ As you can see, acne is not on this list. This means that right now, no clinical trials are taking place to test genetic treatments for acne.

How Safe Is Gene Therapy?

Changing or replacing genes can lead to unpredictable health risks. Previous studies have reported some cases of serious side effects of gene therapy, such as toxicity, inflammation, and even cancer.² This is why medical and research institutions work together with regulatory agencies to ensure that people participating in clinical trials are as safe as possible. The following organizations oversee clinical trials in the United States:

• The U.S. Food and Drug Administration (FDA): The FDA approves drugs for use in clinical trials. In other words, researchers who want to test a gene therapy treatment on patients have to ask the FDA for permission.
• The National Institutes of Health (NIH): The NIH monitors clinical research and provides protocols (procedures to follow) for conducting clinical trials. In other words, researchers who want to test a gene therapy treatment on patients have to follow procedures established by the NIH.
• The NIH Recombinant DNA Advisory Committee (RAC): The RAC reviews protocols (standard procedures) for genetic treatments. In other words, researchers who want to test a gene therapy treatment on patients have to follow procedures approved by the RAC.
• The Institutional Review Board (IRB): Each hospital or university that conducts clinical trials has its own IRB, which reviews all proposed research on people to ensure the research is ethical. In other words, researchers who want to test a gene therapy treatment on patients have to obtain approval from the IRB at their hospital or university.
• The Institutional Biosafety Committee (IBC): Each hospital or university that conducts clinical trials has its own IBC. The IBC reviews all proposed research involving biological materials to ensure the research is safe for both patients and for the researchers and/or doctors. In other words, researchers who want to test a gene therapy treatment on patients have to obtain approval from the IBC at their hospital or university.^1,2

Is Gene Therapy Ethical?

Some government officials and scientists question whether gene therapy is ethical (morally right).

When it comes to changing the genes in a person’s somatic cells (cells in non-reproductive organs, such as the skin, brain, or kidneys), most scientists agree that gene therapy is ethical. This is because changes in the somatic cells only affect that individual, but do not get passed on to his or her children. In other words, we are not changing the DNA of future generations of humans when we perform gene therapy on somatic cells.

On the other hand, changing the genes in a person’s germline cells (reproductive cells like a sperm or egg) is a subject of intense debate around the world. The issue is that changes in germline cells get passed on to the children of the person who receives the treatment. The idea of changing the DNA of future generations of humans makes many people nervous. In the U.S., as in many other countries, scientists cannot use government funds for germline gene therapy research. In addition, the FDA refuses to even look at proposals to test germline gene therapy on patients.^1,18

The Bottom Line

While genetic treatment has become a reality for a small number of life-threatening diseases, no such treatment is yet on the horizon for acne. Intensive research into genetic treatments for many other diseases gives us reason to hope that scientists will soon develop the tools to start exploring gene therapy for acne. If and when this day comes, a genetic treatment could put a dent in acne, but is unlikely to completely eliminate it, since acne is likely caused by more than just genes.

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