Meet the Researcher: Dr Poonam Thakur on prioritising preclinical research
In this new series from Cure Parkinson’s, we’ll be hearing directly from the scientists putting our funded research projects into action. From learning about their career journeys, to getting an inside look at their studies, we’ll discover how their work aims to support people living with Parkinson’s.
In our first interview, Dr Poonam Thakur, an Assistant Professor based in India, discusses the value of preclinical research, her experience studying repurposed drugs for Cure Parkinson’s – and why it is vital for scientists to engage with the public about their work.
How do you decide to pursue a research career? For Dr Poonam Thakur, this choice came around by surprise. “I was the first person to go to university in my family, so I knew absolutely nothing about research until I did my master’s degree,” Dr Thakur explains. “When I did my thesis, I just chose a supervisor in my department and a lab who would take me.”
Yet when studying Biophysics at Panjab University in India, Dr Thakur discovered her passion for tackling research challenges. One of these was Parkinson’s – an area that Dr Thakur began to work on while completing her PhD. “I really fell in love with the topic,” she says. “And I’ve stayed with it since.”
Her research on Parkinson’s took her from transformative postdoctoral work in Sweden and Goethe University in Germany to winning a Junior Scientist Award for best research in the field of Parkinson’s from the International Parkinson’s and Movement Disorder Society.
Now back in India as an Assistant Professor at the Indian Institute of Science Education and Research (IISER), Dr Thakur’s passion for investigating Parkinson’s continues as she leads the Thakur Neurodegeneration Lab.
“Whatever we do, should in some way, benefit the Parkinson’s community”
Dr Thakur’s lab is focused on developing a better drug development pipeline, with a focus on preclinical or laboratory research. Preclinical research is a vital step for evaluating the safety and effectiveness of drugs before they go into a clinical trial; the stronger the evidence for a drug, the more likely it is to succeed in a trial. “Almost 90% of drugs fail in clinical trials for neurological disorders,” she points out. “Therefore, it’s very important that we evaluate targets for drugs in very robust systems, as well as in multiple systems, before we take them into clinical trials.”
This focus on preclinical research is what drew Dr Thakur to successfully apply for and receive Cure Parkinson’s second annual iLCT Pipeline Acceleration Grant – our funding programme which commissions the preclinical research necessary to move promising drugs closer to clinical trials.
For her study, Dr Thakur’s lab is evaluating two drugs – probucol and chlorogenic acid – in models of Parkinson’s to evaluate how easily these compounds access the brain and whether they have a protective effect on the dopamine nerve cells (neurons) lost in Parkinson’s.
Probucol, a medication currently used to treat high cholesterol, is suggested to reduce inflammation as well as improve issues with energy production in cells – two drivers of Parkinson’s progression.
Chlorogenic acid is a naturally occurring compound found in coffee as well as other foods. Researchers believe it may help reduce the build-up of the protein alpha-synuclein, a protein thought to be a hallmark and driver of Parkinson’s.
Testing repurposed drugs comes with advantages and disadvantages. On one hand, Dr Thakur highlights that “the clinical safety and efficacy of the drug is proven – so if they do go to a clinical trial, the first phase can be done much quicker because the drugs are already approved on humans.” However, she cautions that “even though some drugs are working great for one condition, in the case of neurological disorders, we have to ensure that drugs can penetrate the blood-brain-barrier,” – the protective layer of cells surrounding the brain, which controls what comes in and out.
This can be a challenge in research, she says. “While the drugs may be good for another condition, if they can’t penetrate the brain in a reasonable enough dose – they are not going to be useful for Parkinson’s.”
Furthermore, many drugs that are aimed at neuroprotection will only be able to stop or slow progression – meaning that in order to be most effective, they should be given to people in the early stages of their Parkinson’s. However, this may currently prove difficult without strong methods for early detection.
That said, Dr Thakur is hopeful that her study will yield important insights for people with the condition. “It is really my personal goal that whatever we do should in some way benefit the Parkinson’s community,” she explains. “If the outcome in our preclinical evaluation is successful, then I’ll be very happy if any of these drugs go to a clinical trial. For me to contribute to any benefit for people with Parkinson’s, will give me immense satisfaction.”
Levelling the research field
An important aspect of Dr Thakur’s study on probucol and chlorogenic acid is also studying whether there are any sex-specific differences in responses. To do so, she will be testing the compounds in both male and female mice.
“Historically, female populations have been excluded from preclinical research, as well as clinical evaluations,” highlights Dr Thakur. “So, in my lab, I have always made it a point to study both sexes.” She underlines that men and women can react differently to Parkinson’s medication, which is vital to study. “It’s important to understand how the clinical presentation of males and females differ from each other, especially as it’s increasingly clear how drugs interact with our internal hormonal system is going to have an impact on what the drug will do to your body,” she adds.
It’s an aspect of Parkinson’s research that she feels strongly about, having seen first-hand how the lack of research about women experience’s living with the condition has trickled down to all areas of research.
One anecdote she shares is “whenever we make presentations, in our slides we want a picture of what a typical person living with Parkinson’s looks like, and I was always forced to use a picture of a man,” she says. “In the last few years, I have started to find that I can pick a picture of a woman – it just didn’t seem to exist for the longest time.” After all, she says, “it would really be a blind spot to not consider the most basic and clear stratification of the population when developing drugs.”
Overcoming challenges
Working in research has not come without its challenges. When she joined the IISER to start her lab, it was March 2020 and the COVID-19 pandemic instantly halted any lab activities. Dr Thakur laughs, “I joined on a Monday, and by Friday there was a nationwide lockdown.”
Unable to do experiments, Dr Thakur instead used this time to focus on one of her passions – science communication. This has involved writing articles for newspaper columns, mentoring junior colleagues, as well as creating an outreach programme to help promote neuroscience among undergraduate students with webinars and workshops.
Reflecting on this time, Dr Thakur is proud of what she accomplished. “I still draw lots of satisfaction looking back because I was able to have a lot of impact,” she notes. “Even now, many people are still in touch with me from the work that I did back then.”
Communicating with the general public is a skill she thinks all early career researchers should develop. “Sometimes, when we are working in the lab with just solutions and tubes, we don’t always know if our work can have any impact in the field,” she points out. Therefore, she says it’s critical to listen to and engage with patients and other researchers. “It’s very important to network with peers and non-peers, and bounce ideas off each other – maybe that’s how the next breakthrough will happen,” she says.
Future of Parkinson’s research
Looking to the future, where does Dr Thakur think the future of Parkinson’s research should be headed?
“I think understanding different needs for different sub-populations, and trying to work with combination therapies, could be some of the ways in which we can progress in the future,” she answers. “We probably need solutions that are tailored to smaller subgroups of people, which may not be applicable to entire populations.”
Communication between different scientific fields could also play an important role, she adds. “We work in silos and we probably don’t brainstorm together as a community enough for us to being together our ideas and put it into action,” she says. “So, the answer probably lies in collaborating better and listening to people with Parkinson’s perspectives when designing trials and studies.”
Parkinson’s, as Dr Thakur explains, has presented particular difficulties to the research community. “Medical science has advanced so much. It’s frustrating that with Parkinson’s, we have lots of preclinical success but very little clinical success,” she explains. “The field is showing a challenge to us, saying: ‘Hey, this is unsolved. What can you do about it?’”.
It’s clear to Dr Thakur, however, that Parkinson’s is a challenge her lab is ready to try and meet.
