17-Nov-2021: Indian researchers develop better therapeutics to treat Autism Spectrum Disorder

A group of Indian researchers have developed a compound called “6BIO” that can provide a better method to treat Autism Spectrum Disorder (ASD). They have determined the potency of the compound in a pre-clinical mice model. This is the first compound that has been proved in pre-clinical evaluation to have the potential for improving daily activities like learning and recollecting new tasks in patients with ASD/ Intellectual disability (ID).

Autism Spectrum Disorder (ASD) is one of the major issues causing a tremendous burden to our society. Yet, it does not have an appropriate pharmacological or genetic method to treat ASD/ID. Current therapeutics to treat ASD aims to alleviate symptoms such as epileptic seizures or sleep issues but not to treat the multiple problems of ASD/ID. A major challenge in finding better therapeutics to treat ASD is the potency of the drug to help the patients to perform their daily activities with efficiency close to that of a healthy person. Achieving this is particularly difficult after a certain age, especially from the mid-childhood stages.

In the present work, Vijaya Verma and other authors from Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), an autonomous research institute of the Department of Science & Technology (DST), Govt. of India, have demonstrated the potential of 6BIO, to treat ASD/Intellectual disability (ID) in a pre-clinical mouse model called Syngap1+/-. Using behaviour and electrophysiology techniques, the team of scientists have shown in a research published in the Experimental Brain Research that the administration of 6BIO restores the neuronal function, learning and memory, and reduces epileptic seizures in Syngap1+/- mice.

The authors of this study Vijaya Verma, M. J. Vijay Kumar, Kavita Sharma, Sridhar Rajaram, Ravi Muddashetty, Ravi Manjithaya, Thomas Behnisch and James P. Clement, identified 6BIO synthesised in JNCASR and found that it restores neuronal function, learning and memory, sociability and reduces epileptic seizures. The other novelty of this study is that 6BIO restored the neural functions not only when administered during development (equivalent of baby (1-2 years) and childhood stages (3-6 years)) but also after mid-childhood (7-11 years) when most of the brain regions are considered to have formed properly.

Previous studies have attributed disruption in optimal brain development, mainly neuronal connections, during the early stage of development (i.e., babies/childhood) as one of the causes of ASD/ID. Due to the altered brain development, information processing becomes aberrant and understanding simple tasks becomes exceptionally challenging for patients with ASD/ID. Using electrophysiology, which helps understand how neurons communicate, and behaviour experiments, which indicates the overall brain function, the JNCASR team has shown that 6BIO can restore the information processing in the pre-clinical mouse model. Thus, 6BIO has a strong potential for therapeutics to treat ASD/ID. All the behaviour and electrophysiology work was performed in Dr James Clement’s lab at JNCASR.

Patients with ASD still struggle to perform everyday activities without assistance from others as they are unable to learn and recollect new tasks. Data from the current study indicate that 6BIO can help children with ASD learn and recall, be social, and alleviate other symptoms such as seizures or sleep issues. Thus, the compound, 6BIO, can be a better therapeutics option to treat ASD.

4-Aug-2021: INSPIRE faculty fellow develops human-based models to study neurodevelopmental disorders such as autism

Dr. Yogita K Adlakha, an Inspire Faculty Fellow, has developed human-based models to study neuron development and neurodevelopmental disorder such as autism which can help design treatment strategies for such brain disorders.

Since decades, animal models have been used to understand brain-related disorders, and the drugs which function in animal models have failed in clinical trials. The dearth of human models has led to lack of knowledge of the pathophysiology of such disorders, an essential requirement for designing their treatment strategies. Therefore, Dr. Yogita K Adlakha, a recipient of INSPIRE Faculty fellowship instituted by the Department of Science and Technology (DST), filled this gap by generating human-based stem cell model to understand brain development and dysfunction at the National Brain Research Centre, Manesar, Haryana. Currently, she works as a Scientist at Translational Health Science and Technology Institute, NCR bio-cluster, Faridabad.

Along with her research group, she established a protocol from India for the first time by generating and producing induced pluripotent stem cells (iPSCs) from human peripheral blood. They have further refined the protocol of differentiation of iPSCs into the brain-specific stem cells, i.e., neural stem cells (NSCs).

Her group has contributed immensely in understanding the role of microRNA in the neural stem cell fate, which revealed how certain small non-coding RNAs called microRNA, which do not form protein but regulate expression of other genes, can enhance differentiation of neural stem cells into neurons. Her research has contributed to expanding the knowledge of neuron development and the role of small non-coding miRNA in brain-specific stem cells fate, thereby changing the face of neuroscience and stem cells.

Dr. Yogita filled this gap and developed a human-based model that could help study how brain develops, particularly the neurons, and what goes awry during brain development leading to cognitive decline, impairment in language, and social interaction. Along with her group, she derived induced pluripotent stem cells (iPSCs) from human peripheral blood and differentiated them into neural stem cells (NSCs). Since levels of microRNA-137 are less in neurodevelopmental disorders such as ASD and ID, her study demonstrates crucial roles of this miRNA during human NSC fate determination with an elaboration of underlying molecular mechanisms. This study was published in the journal “STEM CELLS”.

Her study provides the first evidence that a brain enriched miRNA-137 induces neuronal differentiation and inhibits proliferation using human neural stem cells derived from iPSCs. During the study, it was observed that miRNA-137 not only accelerates mitochondrial (powerhouse) biogenesis but also induces oxidative phosphorylation, generating ATP or energy currency of the cell. This resulted in increased mitochondrial content, which is actually necessary for the newly born neurons. Decrease in proliferative capacity of NSCs with age leads to compromised regenerative ability of the brain. The findings of her study by revealing the NSC differentiation induced by miR-137 can facilitate the design of treatments for aging-associated neurodegenerative diseases and ASD and ID.

Decrease in proliferation of brain-specific stem cells with age leads to compromised regenerative capacity of the brain. In her present work, she proposes that differentiation of brain-specific stem cells induced by a small non-coding miRNA may promote the design of treatments for aging-associated neurodegenerative diseases and autism.

“My research using DST INSPIRE fund has definitely contributed to expanding the knowledge of neuron development and neurodevelopmental disorder such as autism and the role of small non-coding miRNA in brain-specific stem cells fate,” adds Dr. Yogita.