New Delhi: Researchers at the Indian Institute of Technology (IIT), Madras, Tel Aviv University and Columbia University are studying a rare genetic brain disease called ‘GNB1 Encephalopathy’. The researchers are trying to develop a drug to treat it effectively. With less than 100 documented cases worldwide, ‘GNB1 Encephalopathy’ is a kind of neurological disorder which affects individuals in the foetus stage.
Scientists say delayed physical and mental development, intellectual disabilities, frequent epileptic seizures, are among the early symptoms of the disease. The researchers stated that since genome-sequencing is an expensive procedure, not many parents opt for it early on.
According to Haritha Reddy, a former PhD scholar at IIT Madras, a single nucleotide mutation in the ‘GNB1’ gene that makes one of the G-proteins, the ‘Gß1 protein’, causes this disease.
“This mutation affects the patient since they are a foetus. Children born with ‘GNB1’ mutation experience mental and physical development delay, epilepsy (abnormal brain activity) and movement problems. To date, less than a hundred cases have been documented worldwide,” Reddy said.
“However, the actual number of affected children is probably much greater as diagnosis is not widely available since it requires a sophisticated and expensive procedure,” Reddy who is currently in Tel Aviv said.
“Every cell in the human body has a wide variety of signalling molecules and pathways that help in communicating with other cells and within itself. The major signalling mechanism used by cells is ‘G-Protein Coupled Receptor’ (GPCR) signalling,” Reddy added.
The GPCR is a receptor that receives a signal (eg A hormone, light, neurotransmitter) from the outside of the cell and transduces it to the inside of the cell.
“GPCR is present in the cell membrane and has a G-protein (aß) attached to it from inside the cell. G-proteins are the immediate downstream molecules that relay the signal received by the GPCR. These G-proteins are present in every cell, and any malfunction will cause disease,” explained Reddy.
According to Amal Kanti Bera, Professor, Department of Biotechnology, IIT Madras, as ‘GNB1 encephalopathy’ is a rare and less-known disease, not much research has been done on this.
“We don’t know the mechanisms that underlie the disease. We don’t know how to treat this disease. Therefore, it is import to do research on GNB1 encephalopathy. We have a long way to go. It is not easy to develop a drug for treating this disease effectively,” Bera informed.
“We are in the process of developing preclinical animal models of this disease. Hopefully, in three years we will be able to develop personalised disease models which will be useful in research and drug screening,” Bera added.
The strong neurological impact of GNB1 mutations indicates that ‘Gß1’ is involved in specific aspects of neuronal signaling. A recent proteomic study identified strong link between human epilepsies and ‘Gß1’ protein levels in different brain regions.
Nathan Dascal, Professor, Tel Aviv University, explained that as the developmental issues start at the fetal stage, gene therapy is the most plausible option to alleviate the effects of the mutation. However, the development of this complicated procedure will take many years and great investment of funds.
“On the other hand, epilepsy can be treated using specific drugs to increase the patient’s quality of life. To treat epilepsy, specific targets have to be identified. Most epilepsy cases are caused due to altered ion channel function. Ion channels are proteins that underlie the electrical activity of neurons and heart cells,” pointed out Dascal.
“It is also possible that a combination of already existing drugs helps in a customised treatment line for the rare disease. Like in case of Covid, no new drug was found but already available drugs became part of treatment protocol,” Dascal added.
