Gene Therapy in Parkinson’s Disease - The Method and Benefits

Introduction:

Genes are the basic units of heredity. Researchers have constantly been trying over the years to implement gene therapy for the treatment of various conditions. As a result, gene therapy has been successful in certain disorders which are caused due to a single well-known fault in a particular gene. In such cases, gene therapy is carried out by introducing a healthy gene into the patient’s cells. The cell utilizes the newly introduced healthy gene to make healthy proteins that reduce symptoms or cure disease. Parkinsonism refers to a condition of the nervous system involving the progressive destruction of brain cells resulting in movement-related complications, stiffness of the body, and shaking of arms and legs. Various clinical trials have been implemented to facilitate gene therapy in treating parkinsonism.

What Is Parkinson’s Disease?

Parkinson’s disease is a disorder of the nervous system which affects the body parts controlled by nerves and is caused due to the dysfunction or damage of nerve cells inside the brain that produces dopamine. Dopamine is a chemical messenger that transfers signals within the brain's nerve cells and from the brain cells to other parts of the body. Dopamine plays a significant role in regulating a person’s movements, memory, learning, motivation, sleep, and emotional responses. The major symptoms seen in patients with Parkinson’s disease are trembling hands and legs, slow movements, stiffness in the body, loss of balance, and decreased ability to perform actions like smiling, talking, blinking, and writing.

What Is Parkinsonism?

Parkinsonism is a generalized term used to indicate a group of nerve-related disorders with symptoms similar to Parkinson’s disease, like slow movements, trembling hands and legs, body stiffness, and loss of balance. Parkinsonism includes several nerve-related disorders with similar symptoms, out of which Parkinson’s disease is the most commonly affected condition. The major difference between Parkinson’s disease and parkinsonism is that Parkinson’s disease is caused due to damage or destruction of the nerve cells in the brain, whereas parkinsonism can be caused by various factors like severe head injuries, side effects of certain medications, toxins, and any nerve-related conditions.

What Are Genes?

Genes are the basic units of heredity. They carry unique genetic information often used in the cells to produce new proteins. Genes play a major role in determining the physical appearance of a person. They are responsible for the inheritance of mental and physical traits of individuals from their parents and help pass the traits from one generation to the next in a family. Sometimes, genes also play a role in developing a particular disease or condition. If a person inherits a defective gene, he may have the possibility to develop a range of diseases.

What Is Gene Therapy?

Gene therapy is one of the latest advancements in medicine, which refers to treating certain diseases with the help of healthy genes instead of medicines. Gene therapy can be performed in several ways based on the type of disease. The most common gene therapy method is by introducing a healthy gene into the patient’s cell, which would instruct the body to produce the missing proteins needed for organ functioning. Another form of gene therapy involves the replacement of a defective gene with a copy of a healthy gene. Gene therapy can also be done by deactivating a gene that does not function properly.

How Is Gene Therapy Used in Treating Parkinsonism?

Researchers believe that gene therapy can be useful in treating parkinsonism based on the fact that this therapy can prevent the damage and death of the dopamine-producing cells in the brain. Researchers point out the benefit of this therapy over the other conventional treatment measures, as gene therapy can slow or stop the disease, whereas conventional treatment methods can only reduce the symptoms of the disease. The current research on gene therapy and parkinsonism aims to deliver healthy genes directly into the affected nerve cells of the brain.

How Gene Therapy Delivers Healthy Genes Into the Brain?

Gene therapy uses a carrier agent called a vector to deliver healthy genes into the brain cells to treat parkinsonism. Genetically modified viruses are the commonly used vectors to deliver therapeutic genes to the brain. These viruses are modified in such a way that it does not cause any infection and does not spread to parts other than the targeted area of repair. Each viral particle will enter only one cell (area of target) and introduce the therapeutic genetic material. Even though the virus disappears after delivering the genetic material, the therapeutic effect of the genetic material remains in the cell of the patient for a very long time. Adeno-associated viruses and lentiviruses are the commonly used vectors in delivering therapeutic genes to Parkinson's patients.

What Are the Methods of Gene Therapy Used in Treating Parkinsonism?

Many clinical trials have been going on to implement various outcomes of gene therapy in the treatment of parkinsonism. They are as follows:

• Proteins That Increase Dopamine Production: This trial is based on the concept that gene therapy would instruct the undamaged brain cells in the Parkinson's patient to produce dopamine which would restore the functioning of the damaged brain cells. Researchers believe that achieving normal levels of dopamine would improve the transmission of signals within the brain cells and also from the brain cells to other parts of the body. This would help in improving the person’s memory, movement-related problems, and other symptoms of the disease. This form of gene therapy can replace the conventional medications which are taken to replace the reduced amount of dopamine in the brain. Gene therapy can overcome the side effects of conventional medications like dizziness, confusion, agitation, thought abnormalities, and hallucinations (experiencing something that is not present).

• Restoring Brain Cell Activity: In parkinsonism, cells in the basal ganglia region of the brain tend to become hyperactive. The basal ganglia are the region of the brain that consists of a network of brain structures that play an important role primarily in controlling body movements and also other functions like learning and emotional processing. Researchers believe that increasing the levels of enzymes produce gamma-aminobutyric acid (GABA). GABA is a brain chemical that plays a major role in controlling the hyperactivity of the nerve cells by stopping nerve signal transmission. However, the use of enzymes to control the hyperactivity of nerve cells has not shown many effective results. Hence the use of certain genes and proteins to control the activity of the hyperactive nerve cells of the basal ganglia region is being developed.

• Role of Growth Factors: Growth factors are naturally occurring substances in the body that help in cell growth, wound healing, and repairing and regenerating tissues. Researchers believe that introducing growth factors can help in preventing nerve cell damage and rejuvenation of the dying nerve cells. The introduction of growth factors has shown improvement in the disease progression in patients. However, the introduction of growth factors using newer ways of administration and site of delivery is being carried out to bring out the best outcome.

Conclusion:

Even though gene therapy has many advantages over conventional treatment methods, it is still under clinical development. However, gene therapy has shown great efficiency in the management of parkinsonism. In addition, the side effects of the drugs used in treating parkinsonism and the reduced potential of medications to treat the disease at severe stages have made gene therapy a reliable option to treat parkinsonism. Hence, with more clinical trials and better advancements, gene therapy stands as a hope for the new generation of clinically relevant treatment options for parkinsonism.