Gene Therapy For Immune Deficiency – Is It a Reality or Still an Experiment by Dr. Sagar Bhattad

We are all aware of one too many “genetic” diseases and defects that can change a person’s life overnight. A person is born with these defects, but they may surface later or even take years before a doctor can accurately diagnose them. When they do confirm it is a genetic issue, they mostly tell us that there is no cure for it, and we should learn to live with it.

Gene therapy aims to break through this barrier and change the “defective genes” causing the health issue in an individual. Gene therapy is not new. It has been around for some time and some doctors even use it to treat some ailments instead of prescribing drugs and treatments.

Initially, when doctors started using gene therapy to treat certain ailments –

• They would introduce a new healthy gene into the body, to help fight a disease the existing immune system is unable to fight.
• In case of a faulty gene, introduce a non-faulty gene to take the defective gene’s position and improve the immune system.

Genome Editing – A Type of Gene Therapy

With time and continuous research, genome editing has come into play. It introduces molecular tools which will change the DNA in the individual. So, in case of an immune deficiency due to a defective gene, genome editing will not try to replace it but repair it instead. The molecular tools will change the way the disease-causing gene is functioning inside the body.

The aim of genome editing is to

• Correct the altered gene that is causing the disorder, to help that gene function properly.
• Turn a specific gene “on” to fight a disease.
• Turn a specific gene “off” when it is not functioning properly.
• Remove a part of the DNA that is interfering in the way a gene is functioning, thus causing a disease.

Is Gene Therapy For Immune Deficiency an Effective Treatment Option?

Gene therapy is still in its infancy stage. A lot of research is still going on to find ways to use this therapy to help various genetic issues including immune deficiency.

In Immune deficiency, the immune system does not function to its fullest potential or under-performs, resulting in frequent infections and diseases. The immune system fails to recognize and fight foreign pathogens, thus resulting in multiple health issues. It can be present from birth or sometimes even derived.

The aim is to replace this defective gene with a healthy one to help the immune system function as expected. This in turn will “cure” the immune deficiency in the child.

Though some trials have been successful, there are several risks involved as well. Gene therapy is still not a reliable treatment for immune deficiency. Research is still going to find ways and means to replace or repair the defective gene, without altering too many of the other genes.

There are various gene therapy drugs produced with permission, which help doctors successfully treat certain chronic diseases. However, these are all still in the trial phase and one cannot really predict if they will be successful in every area attempted.

[Read : Primary Immunodeficiency in Children]

Why is Gene Therapy Done?

In many diseases or disorders, the genes are responsible. Genes are something we derive from our parents. When a parent passes on a defective gene to their child, they are effectively passing on a disorder or a disease to the child.

The genetic makeup of the child is the basis for the child’s health and everything else. When a person has a defective gene, no medicine can cure the condition or change the gene. Gene therapy aims to break through this barrier and change that defective gene. It aims to change or repair the gene causing the disorder either by over-performing or under-performing.

Here, let’s break down this gene therapy further

• The body consists of critical proteins which carry out various functions.
• A person’s genetics carries out the instructions for designing these proteins.
• A defect in a gene will affect how the protein is made and that protein’s function.
• Gene therapy aims to fix or repair these proteins that are causing a disorder, or the immune system to malfunction.

Gene therapy can work in the following ways

1. If a faulty gene is causing the protein responsible for immunity to malfunction, gene therapy will try to replace this protein. Gene therapy will introduce a normal copy of this particular protein so that the healthy gene can take over and suppress the faulty gene. As a result, the disease will improve or can even be completely cured.
2. Another possibility is that gene therapy can introduce a completely different gene, which will instruct the protein to function normally despite the genetic defect.

The main reason behind gene therapy is the desperate need to tackle genetic disorders where the origin cannot be really identified. Genetic issues had the doctors stumped for solutions for decades. Today. Gene therapy can help with such disorders and produce lasting results.

People suffering from genetic disorders which might cause various other health issues or heavily compromise their quality of life can benefit from gene therapy.

Are There Any Risks in Gene Therapy For Immune Deficiency?

Yes, in its current state, gene therapy has its own set of risks. With gene therapy, science is trying to alter the genetic makeup of a person’s body. It is trying to change something that occurred naturally.

While in many trials gene therapy has successfully treated the underlying disease, it paved way for many other issues like inflammations, toxicity, and even cancer. A gene does more than one job and this is something scientists are still learning about. The genes in the bodywork together to make you what you are. Gene therapy is technically altering this combination or synchronization.

So during the replacement or alteration of the defective gene, in addition to changing the underlying health condition, it leads to other changes as well. Research is still going on to identify the unique combination and ways to isolate the defect and work on that alone. This is what genome editing is all about. Genome editing “Edits” the gene rather than replacing it fully.

A gene cannot be just injected into the body. It needs to be delivered through a vector, which in most cases are viruses. Some of the risks identified so far with gene therapy are:

1. Targeting Wrong Cells

The virus introduced to target the mutated genes might attack other cells as well. Viruses can affect more than a single type of cell and they might affect healthy cells. This can weaken the body further or create more infections and health issues.

2. Unpredictable Reactions

The new virus is new to the immune system. The immune system can mistake it to be an unwanted pathogen or a threat to the body. If the immune system reacts to this new virus, it will not only kill the vector of the new gene but might increase inflammation in the body. It can even lead to more serious issues like organ failure.

3. Other Infections

The vector for the gene – the virus might cause other infections in the already weak body. Since it is an immune deficiency, the body may not be able to fight it effectively.

4. Tumours

Not inserting the gene into the right spot properly might lead to the formation of a tumour due to the activation of proto-oncogenes in the body.

Many trial cases were successful without any of the above risks. However, many patients reported tumors many years after therapy. The other risks can also harm the patient at any time. Therefore, gene therapy is yet to replace many treatments and become the go-to treatment for many chronically ill patients.

How Should One Prepare For Gene Therapy?

Gene therapy is still not fully available for all. It is still in the research and trial stage. As of now, you can undergo gene therapy for immune deficiency only through a trial. They are still conducting trials to gather sufficient data and to understand the efficacy of the treatment.

When you decide to undergo a clinical trial for gene therapy to treat immune deficiency, here are a few ways to prepare yourself –

1. Get Details

The very first step is to get sufficient details about the entire procedure. Ask your doctor what they will do in this therapy, how long it will last, how many times you need to come into the hospital, how long will it take for results to show and other such details relating to the treatment itself. Since it is still in the trial stage, not many details are available for the common man.

2. Clarify Doubts

If you have any doubts, do clarify them. Never “assume” anything when it comes to an experimental treatment. Yes, they have a good track record with gene therapy in treating an immune deficiency, but you need to be confident and sure about the treatment you are signing up for.

3. Understand Medication Options

There are a number of gene therapy products available to doctors today. Understand which option they are going with and why. Knowing more about the medicine they will give you is very important.

4. Lower Expectations

Yes, only desperation and courage can lead you to sign up for a clinical trial. Do not expect to get better immediately; allow the treatment to take its time. When you lower your expectations from the treatment, your anxiety will also reduce.

What Are the Benefits of Gene Therapy For Immune Deficiency?

Gene therapy aims to break through the barrier set by genes in our bodies. Though they have a breakthrough with gene therapy and clinical trials suggest a positive outcome, it is still under study. Here are a few advantages you can derive from gene therapy.

This therapy can

• Replace a faulty gene that is preventing your immune system from functioning properly.
• Replace or repair a faulty gene that is causing a disease.
• Provide a permanent solution to your immune deficiency, unlike some medications that only suppress the disorder or help with other infections that are a direct result of the immune deficiency.
• Treat a wide range of chronic diseases that otherwise do not have a cure as of today.
• Repairing or replacing the default gene will reduce the chances of the defect from passing on to the next generation.

If researchers succeed, they can create multiples of your DNA and can treat any disease you may get as you grow older.

Gene therapy is still in the clinical trial stage and is not in use for treating various ailments. Only if patients receive gene therapy, can they identify more advantages or benefits.

Are There Any Side Effects of Gene Therapy?

Yes, unfortunately, there are a few side effects to gene therapy if not done properly. One of the biggest side effects of gene therapy that puts a pause on the clinical trials is the development of tumors or cancer after therapy.

Another risk as mentioned earlier is the infections the virus can cause in an already weak immune system. While the therapy might treat the main underlying disorder, it might pave the way to other infections or disorders.

What Are the Conditions Treatable by Gene Therapy?

As of now, gene therapy is still under research. Scientists are trying to find effective ways to introduce healthy genes into the infected body. When they find a suitable method to introduce the gene safely, chances of successfully treating the condition will be on the rise.

As of today, gene therapy can treat the following conditions:

1. SCID or Severe Combined Immune Deficiency
2. Leukemia
3. Haemophilia
4. Blindness due to Retinitis Pigmentosa

Gene therapy had successful results in clinical trials for the above-mentioned disorders. More are under research and once scientists find ways to inject the healthy gene into the body, they can try to cure more ailments. Unless it is side effect free, even if the effects surface only a few years after treatment, gene therapy will take more time to test its efficacy in other areas.

[Read : Leukaemia in Children]

What Can One Expect From Gene Therapy For Immune Deficiency?

When gene therapy succeeds and doctors start using it to treat various conditions, we can expect the following:

1. The therapy can repair or replace the defective gene in the body, as per the requirement.
2. Genetic diseases need not be genetically transferred anymore.
3. Science can control the genes a child inherits from the parents.
4. If needed, a completely new gene can be introduced into a person to create changes in them (this will become experimental).

Some of the negatives one can expect from gene therapy are

1. Gene therapy can quickly become a dangerous tool if not monitored and controlled properly by the concerned bodies.
2. The genetic makeup of an individual can be controlled and dictated completely.

Just like everything else related to science, there will be advantages and disadvantages. If concerned bodies manage and control well, we can expect a lot from gene therapy. It can help chronic patients live a full healthy life.

Gene therapy is a medical breakthrough, which can change the lives of many children. Since it is still in the clinical trial phase, every parent cannot get access to this therapy for their children. When solid and consistent results are available, gene therapy might help in various ailments. It can be very tough but as a parent, you have no other choice than to wait for now.

When gene therapy is available to the common man, it can change the lives of many children and parents alike.

FAQ’s

1. Can Gene Therapy Affect the Immune System?

Yes, it can. It can have either a positive or a negative impact. If they insert the gene into the right cells, it will have a positive effect on the immune system. If they inserted it into the wrong cells, it would have a negative impact.

Read Also: Biologics For Autoimmune Diseases – A New Treatment For Children by Dr. Sagar Bhattad