As Fatima Sana Shaikh brings epilepsy to social media, can gene therapy help?

When Fatima Sana Shaikh talked about her battle with epilepsy, she perhaps normalised the conversation around what is actually a very common health condition. However, given the taboos around it, considering it manifests as sudden seizures and spasms, common people liken it to curse or possession supernatural forces. They fear it without understanding it and worry about passing it on to the next generation. Of course, very few bother to know that research over the years has resulted in drugs and therapies that have helped in managing the disease and improving the condition of patients. Earlier this year, research from the School of Medicine showed how a newly-developed gene therapy can treat Dravet syndrome, a severe form of epilepsy, and potentially prolong survival for people with the condition.
So what exactly is epilepsy?
Epilepsy is a brain disorder caused abnormal activity in the brain neurons. “Epilepsy refers to the condition where there is hyperactivity of the brain cells or sudden bursts of electrical activity in the brain, resulting in spasm-like attacks. These can vary from seizures or periods of unusual behaviour along with abnormal sensations and sometimes loss of awareness. The reason for this hyperactivity of a group of neurons or a group of brain cells is because of chemical changes in neuropeptides present in the brain or in the ions,” says Dr Atul Prasad, Principal Director and HOD Neurology, BLK Max Super Speciality Hospital.
“Epilepsy is an umbrella term which refers to a tendency of an individual to get recurring seizures. It may be genetic or acquired. The genetic type may be inherited from family members, especially when the patient is a result of a consanguineous marriage, or marriages within the relatives. In such cases, even the hory of dant family members, like first and second cousins suffering from seizures, holds importance. Epilepsy may also be seen after various incidents like trauma, infections, metabolic durbances, drug abuse and so on. When no such underlying cause can be found, then epilepsy is termed an idiopathic infection that can cause seizures. But what people need to know is that viral infections, particularly the kind caused the herpes virus, can induce epilepsy. In the last few years, COVID infection has been seen to increase the burden of epilepsy causing direct or indirect brain strokes, venous thrombosis and so on,” says Dr Ishu Goyal, Associate Consultant, Neurology, at Sir HN Reliance Foundation Hospital.
“Drug abuse or alcohol misuse and a lack of oxygen during birth can be the cause of epilepsy because of scrambled electrical signals in the brain. These scrambled electrical signals cause abnormality in the brain activity. Being a very common condition, almost 1 per cent of our population suffers from epilepsy with the number rising rapidly in the recent past because of the pandemic,” says Dr Prasad.
“Epilepsy is generally caused over and abnormal excitation of cortical neurons, predominantly situated in the temporal lobe. Our brain conss of two major groups of neurotransmitters which are excitatory and inhibitory neurotransmitters. Overactive excitatory neurotransmitters and underactive inhibitory ones predispose a person to seizures. Ironically, even though approximately 10 million people suffer from epilepsy, people hesitate to come forward and seek medical help,” adds Dr Goyal.

What is gene therapy and how does it help?
It should be emphasised that it is an easily controllable disease with medication. “Many new and advanced drugs are available these days, which have minimum side effects when taken over a long period of time. Also, modern treatments for epilepsy, like surgeries and transcranial magnetic stimulation, are available,” adds Dr Goyal.
A newer form of treatment known as gene therapy has gained popularity recently. “Although it hasn’t been proven to provide treatment in each and every case of epilepsy, studies have been going on around the treatment module. The procedure takes place with the help of viral or non-viral vectors which deliver DNA or RNA in order to target the brain areas causing the seizures. It is done to prevent any development of epilepsy and to reduce or limit the frequency and/or severity of seizures,” says Dr Prasad.
The gene therapy is now in clinical trials. Because most Dravet syndrome cases are caused a mutation in the SCN1A gene, resulting in a reduction in SCN1A protein production, the novel approach is designed to boost production of SCN1A to normal levels. If successful, the approach, called Targeted Augmentation of Nuclear Gene Output, or TANGO, would be the first treatment for the fundamental cause of the disease, a lack of this particular protein in specialized brain cells.

The new research – University of Virginia’s Manoj K. Patel, PhD, and Eric R. Wengert, PhD, and their collaborators – demonstrates how the experimental therapy restores the cells’ proper function and reduces seizures in lab mice. They found that a single treatment with the TANGO therapy rescued the deficits in the interneurons and made them behave like those that naturally had the full amount of the protein. The interneurons, which function to constrain the brain’s excitability and protect against seizures, became more responsive, more active, and better able to do their jobs. As a result, the TANGO treatment decreased seizures.
What are the myths around the disease?
Epilepsy is a central nervous system disorder and can affect any person irrespective of race, ethnic background and age. “Most people believe that patients are unable to take care of themselves, cannot function normally or are mentally incapacitated. The truth is epilepsy is just another disease which can be easily controlled if the patient is encouraged to lead a normal life, go to work, participate in sports and perform daily chores,” says Dr Prasad.
It is also believed that a person suffering from an epileptic attack should be exposed to a strong odour like shoes or socks, which is totally wrong. “People around patients just need to ensure that they don’t hurt themselves. Epileptic attacks are usually self limiting and reduce or go away within a few seconds or a minute or two,” he adds.

How to fight the taboos?
The need of the hour is public awareness about the condition and the steps to be taken to revive a sufferer who doesn’t know what might trigger a bout of attack. “In such circumstances, the person should be made to lie sideways, his/her clothes should be loosened up. Nothing should be inserted in the mouth and nothing should be given to the patient, not even water, till the seizure subsides on its own. Then the patient should be taken to the hospital,” says Dr Goyal.
Patients should further be counselled and consoled that epilepsy is controllable and they can lead as normal a life as possible.