City researchers create mini brains to study spinocerebellar ataxia type 12 in kolkata marwari community
A team of city neurologists and researchers created ‘mini brains’ out of real human tissues and blood vessels to study the trigger for a neurological ailment that affects many, particularly in Kolkata’s Marwari community. ‘Spinocerebellar Ataxia type-12’, a disease that affects motor nerves and seriously hinders movement, is being studied by the researchers, who are now in the process of identifying medicines that could be effective against the disease. The research confirmed an earlier finding that the Marwari community is genetically predisposed to the ailment, and it also threw new light on the ailment by stating that SA-12 affects cognitive abilities.
Inspired by neurologist Hrishikesh Kumar, head of neurology at the Institute of Neurosciences Kolkata, and led by Sumantra Chattarjee, director of the Centre for High Impact Neuroscience and Translational Applications, TCG CREST—where the study is being held—2 ‘human brains’ were created in the laboratory, a first in India, the researchers claimed.
“AS-12 creates serious problems with regard to gait and movement, and it makes the patient lose balance, similar to Alzheimer’s. As the name suggests, it affects the spine and the back of the brain, which plays a major role in movement and coordination. It is caused by gene type 12 and was first found in an Agarwal family. Being a small community, the genetic mutations persisted and remained confined within the community. They are settled in different places and carry the SA12 gene, which is unique and affects particular communities like the Agarwals. It was Kumar who first told me about it, and it got me interested. He set up the research for us. It was a uniquely Indian challenge, and we have so many patients in Kolkata. The research is focused on brain diseases in India, of which SA-12 is an excellent example,” added Chattarji.
The researchers’ aim was to understand how it affects the nervous system. While doctors see the symptoms, they aimed to identify what exactly was going wrong in the patients’ brains. “We can’t go inside a living patient’s brain. So, one creates animal models for pre-clinical trials, and that is how it works traditionally. But medicines developed based on findings from animal model research don’t always work in humans. They often fail in drug trials. So, we needed human brains. Now, you can’t take cells from the brain like other organs since you need to penetrate the skull. So, we developed an alternative process—extracting a piece of skin or blood from a patient to replicate the patient’s brain. It was done through induced pluripotent stem cells that can become any cell in the body. Now, we had a way of creating these cells that we drove to turn into brain cells through molecular biology and other sophisticated methods,” said Chattarji.
The cells were then grown in a Petri dish to develop into a full-fledged human brain that was a replica of a real patient’s brain. “It was developed over months, with all the neurons and brain cells. It is a brain created from the genetic material of a living patient, which was created in our laboratory without touching the patient. Now, we have a diseased brain in a dish and another from an unaffected sibling of that patient,” explained Chattarji.
Both were grown for a comparative study. “We can use sophisticated neurobiological techniques to analyse the 2 brains to identify what’s not functioning properly. We already did that and identified the anomalies. We are still in the process of identifying the nature of the targets we need to work on. It’s the first of its kind in India.”
The gene could be carried either by the mother or the father, said Hrishikesh Kumar. “If the abnormal gene is transmitted to the children, the disease is bound to be manifested in them later in their lives. On the other hand, there is a 50% chance that the children may not inherit the abnormal gene at all. In that scenario, they and their further progeny remain unaffected by the disease. Curiously, even though the community has a strong presence in various other parts of the country, including Rajasthan and Haryana, it is only in Bengal that the disease was more prevalent,” said Kumar.
“We can collaborate with specialists and create an alliance between researchers and clinicians to identify the triggers for several other neurological ailments and look for remedies,” said Chattarji.
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Around 43 types of SA were detected around the world. In India, types 1, 2, 3 and 12 of the disease are the most common.
While the other 3 are more commonly found, SCA-12 is yet to be detected outside the particular community in Bengal.
SCA-12 starts with a mild tremor of the hands and gradually affects walking.
Eventually, it leads to significant loss of limb co-ordination, eye movement co-ordination and slurred speech.
In tertiary care centres of Kolkata, about 5% to 10% of all neurological patients are victims of ataxia.
Even though symptoms can be partially controlled with medicines, SCA still remains incurable. MSID:: 128779733 413 |