Dr. Chandrashekhar Thodupunuri, Founder & CEO, Providence Microbiome Research Center

Autism, also called Autism Spectrum Disorder (ASD), is a neurological and developmental disorder that occurs during embryonic life. It is defined based on social and communication problems and repetitive and restrictive behaviours that can vary in individuals along a continuum of severity. A diagnosis of autism can be made as early as 18–24 months of age, from where characteristic symptoms can be distinguished from typical development and from other delays or other developmental conditions. Unfortunately, Autism is growing exponentially on a global scale. In 2020, the incidence rate of autism in India was 1 in 100 and was predicted to grow to 1 in 10 by 2050. Despite these alarming figures, no established cause and treatment are available.

Bringing a ray of hope through his breakthrough research, Dr Chandrashekhar Thodupunuri, the Founder & CEO of Providence Microbiome Research Center, is on a mission to improve the quality of life of autistic individuals.

The Career Beginning

Dr Chandrashekhar completed his MBBS degree from the Prathima Institute of Medical Sciences. He then pursued Post Graduate Diploma in Clinical Cardiology from Apollo Hospitals. In 2014, Dr Chandrashekhar began practising cardiology. Intermittently, he also completed his MAPS fellowship in the USA, the only comprehensive program for treating medical issues associated with special needs, autism spectrum, and neuro-developmental disorders.

During his medical practice, Dr Chandrashekhar acquired profound knowledge about drug research, clinical trials, and regulatory systems. “This knowledge helped me conduct systematic research into autism and find ways to alleviate it when my daughter was diagnosed with autism spectrum disorder (ASD),” says Dr Chandrashekhar.

Key Research Potential Led to a Career Transition from Cardiology to Autism Research

In autistic individuals, disordered development happens during the fetal stage. Taking this as a lead, Dr Chandrashekhar and his team started looking for possibilities that could be responsible for causing it during pregnancy. “We found two contributing factors: one is umbilical cord blood toxins, and the other is the fetal gut microbiome,” reveals Dr Chandrashekhar. Few studies have reported that environmental toxins can cross the placental barrier, enter the fetus, and could be responsible for neurodevelopmental disorders. Moreover, microbiota transfer therapy clinical trials showed promising results in autistic children. “These facts inspired me to hypothesise that environmental toxins might disrupt man-microbe symbiosis during pregnancy and result in various developmental errors,” declares Dr Chandrashekhar. “Hence, we thought of reducing the toxin load in pregnant mothers to protect the fetal gut microbiome, thereby preventing epigenetic errors responsible for autism.”

N-acetylcysteine (NAC), a glutathione precursor in the antenatal program, could safely remove toxins in pregnancy and play a significant role in preventing autism. FMT in the first three years of life may reverse epigenetic errors by replenishing the gut microbiome and even reverse autism. “This great possibility made me leave my thriving cardiology career and work towards autism prevention,” shares Dr Chandrashekhar, the physician turned scientist.

Providence Microbiome Research Center: A Specially Dedicated Centre for Autism Research

Incepted in September 2020, Providence Microbiome Research Center Pvt Ltd (PMRC) is a start-up recognised under Startup India Scheme. The research at PMRC is solely focused on autism prevention and amelioration. “Our core leadership team comprises scientists with expertise in next-generation sequencing, academic researchers well-versed in animal studies, and medical doctors of various specialities like neurology, paediatrics, psychologists, psychiatrists etc., which is the perfect combination for our vision and mission,” mentions Dr Chandrashekhar.

Unfortunately, the research at PMRC could not be initiated due to the COVID-19 pandemic as the study involves body fluids. “However, we could register our first trial in February 2022,” enthusiastically shares Dr Chandrashekhar. “We also designed a roadmap for three human and three animal studies oriented toward autism prevention during the pandemic.”

Ongoing Research Studies

Currently, PMRC is conducting a clinical trial, Fecal Microbiota Transfer Therapy for Autism, with approvals from St Theresa’s Hospital Ethical Committee and ICMR. This trial explores the relationship between the gut microbiome and human epigenetics and its relevance in the development of autism. PMRC is also conducting some other studies like umbilical cord blood toxicology, meconium microbial population study, and a few animal studies to explore the aetiology and pathogenesis of autism. In addition, PMRC has collaborated with St Theresa’s Hospital, KSBIO Clinserve, Inductive Quotient Analytics, Center for DNA Fingerprinting and Diagnostics-National Genomics Core, Mibiome therapeutics, Agenes Info omics Pvt Ltd, and Bharatiyar University to conduct a series of clinical trials.

Apart from research on the gut microbiome and autism, PMRC is looking at developing a first-in-India microbiota bank (stool bank) with a network of FMT clinics that will serve ulcerative colitis and Clostridium difficile patients for now. These clinics will help individuals with autism, myalgic encephalomyelitis, psychiatric illnesses, and many other neurological disorders after the role of FMT is established in those conditions.

Faecal Microbiota Transfer Therapy & its Potential

According to the research conducted by Dr Chandrashekhar and his team, some microorganisms are vertically transferred from the mother’s uterus (considered sterile until recently) to the baby’s intestine during the fetal stage. Therefore, they hypothesise that this microbial and fetal genome work in unison and direct the complex orchestra of events during fetal development. They call these essential microbes ‘symbionts,’ and the rest of the microbes acquired in life ‘commensals.’ This concept arose from the fact that all biological processes in healthy neonates are in homeostasis. Therefore, any gut microbe that has any role in human health must be present in the neonate’s gut. Furthermore, Dr Chandrasekhar and his team assume that the absence of these symbionts during the fetal stage affects fetal epigenetics and results in disordered neurodevelopment.

Owing to their hypothesis, they are now trying to repopulate these symbionts by doing FMT, which would restore a counterpart of the baby’s genome and normal epigenetics and initiate repair mechanisms, thereby reducing symptoms of autism and aiding in further healthy development.

“Our FMT trials started in February 2022; hence it is too early to comment on efficacy, but we could see an excellent safety profile if donor screening is done scientifically,” states Dr Chandrashekhar. “Though there is good feedback from parents and professionals after FMT, a significant improvement in CARS scoring and reversal of errors in epigenetic testing are needed to make some conclusive statements.”

Current Trends in the Medical Industry

According to Dr Chandrashekhar, the medical profession is advancing rapidly. Research involving the triad of genetics, epigenetics and gut microbiome is expected to show a new avenue or approach to medical practice. He further adds that research involving this triad will bring individualised precision medicine, which has the potential to bring a revolutionary change in modern medicine.

Active Autism Research is the Urgent Need of the Hour

Today, the incidence of autism is increasing exponentially with neither an established cause nor a proven treatment. On top of that, the future predictions about autism incidence look very scary. The trends in autism incidence are direct evidence that the human womb is becoming unfavourable for normal childbirth; hence it is a global responsibility to do active research on autism.

“Currently, we are conducting a series of clinical trials which will hopefully establish the role of environmental toxins & foetal gut microbiome in the development of autism,” shares Dr Chandrashekhar. “In the future, we hope our research will pave the way for autism prevention.”

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