Brain and mental disease act differently on different people, and a broad range of factors account for the differences. Clinical research needs to factor in sex and gender determinants to arrive at workable solutions (and treatments) that have an equal chance of success with women and men. This is where the Women’s Brain Project (WBP)comes in. Aimed at a deeper understanding of brain and mental disease, the Project is working on seeking solutions to Alzheimer’s and dementia for which there is no known cure.
As the global population is aging, the disease is growing on an epidemic scale. Currently, 50 million people live with Alzheimer’s and dementia. It is projected that by 2030, that number will rise to 75 million and by 2050, to 131.5 million.
Founded in 2016 by a group of scientists hailing from various disciplines including medicine, neuroscience, psychology, pharmacy, and communication, WBP aims to:
(1) stimulate debate, both in academia and among the broader public, on gender and sex differences in brain and mental disease;
(2) promote and perform scientific research on sex and gender determinants of brain and mental health;
(3)advocate for the development of sex-specific measures to foster mental health that would lead to a new, personalized way to develop and perform medical treatments, caregiving, and prevention – catalyzing the adoption of a precision medicine approach for brain and mental health.
Since its foundation, WBP has expanded and now includes a broad range of academic scientists, medical doctors, and engineers as well as partnerships with notable associations and think tanks, including Mauli Seva in India, WHAM! and UsagainstAlzheimer in the USA, and the European Academy of Neurology (EAN) in Europe. WBP acts as an official advisor of the Mary Horrigan Connors Center for Women’s Health & Gender Biology at Brigham’s Hospital, in Boston.
To find out more about this project, Impakter recently talked to one of the project’s founders, Maria Teresa Ferretti who is one of the WBP Co-founders and its Chief Scientific Officer. A graduate of McGill University (Canada) and with a Ph.D. on the topic of inflammation in Alzheimer’s disease, she works on biomedical research in the field of Alzheimer’s disease and was also a group leader at the University of Zurich/Zurich Neuroscience Center (Switzerland). She is currently an external teacher at the Medical University of Vienna.
You are one of four founders of the Women’s Brain Project. Can you tell us how it happened? How did the four of you get together, what was your role in conceptualizing the project?
Maria Teresa Ferretti: In 2016, while working at the University of Zurich as a group leader, I was contacted by a Swiss journalist for an interview on Alzheimer’s. As a young group leader who had just established herself in academia, I was delighted and agreed. To my surprise, the journalist was not interested in my studies on microglia and immunity in Alzheimer’s at all. She started asking me questions about sex differences in Alzheimer, and why more women than men are affected by it (2/3 of patients are women). I had no idea. At that point, I realized how little I knew about it, and resolved to fill this gap as soon as possible.
A few days later, I received a phone call from my friend Antonella, a former colleague from the University of Zurich who, at the time, was working for a regulatory agency for drug approval. [Ed. note: She is Dr. Antonella Santuccione Chadha, one of the Co-founders and WBP CEO. ] She told me she had a proposal for me, something that would change my life.
During a meeting she had attended together with Gautam a few days before, the issue of ‘more women than men’ was presented by the American organization ‘UsagainstAlzheimer’. [Ed. note: Gautam Maitra, Fil. Lic. Stockholm University, WBP Co-founder, responsible for external affairs, is a chemist and regulatory affairs professional, member of the European Advisory Council of the Regulatory Affairs Professionals Society and serving as a regular instructor on Regulatory Affairs at the Swiss Federal Institute of Technology.]
This rang a bell for Antonella. As a medical reviewer, she was struck by the number of sex differences in drug effects (including side effects) and how little they were taken into consideration in the review process. She wondered how much these differences could affect drug design, especially in Alzheimer’s, but possibly in general in all diseases of the brain. So she came up with the idea of creating a Swiss organization focusing on this, with a strong scientific basis, to do more research and raise awareness on this topic.
Gautam, who at the time was working as a regulatory affairs specialist for a pharmaceutical company in the space of Alzheimer’s, immediately agreed. Antonella was now recruiting me, as the basic scientist of the team, and next, she contacted Annemarie, a health psychologist. [Ed.Note: Annemarie Schumacher Dimech, Dr. Phil. WBP President and Co-founder, with a Ph.D. at the University of Bern (2010), currently at the University of Lucerne where she developed and is heading its program of further education in Palliative Care.]
The four of us were all working in the field of mental health, with a focus on dementia, and each one of us, independently, had been ruminating on this topic of sex and gender differences for a while. As a basic scientist, I realized how little my colleagues (and even I, to some extent) were considering sex in animal experimentation; many colleagues were running experiments often with mice of one sex only, usually males.
Annemarie, who at the time worked as a researcher at the University of Applied Sciences St. Gallen, was passionate about gender roles and how they, especially in caregiving, can impact one’s mental health; caregiving is way more common in women and yet this was not really considered in research and policies.
I was struck by the coincidence – first the journalist, and now Antonella and the non-profit idea. I like coincidences (after all, they are a dimension of the beauty of the world, according to Milan Kundera), but I was also a bit skeptical at the beginning.
May I interrupt? You are referring to one of my favorite novels, The Unbearable Lightness of Being, and I looked up the exact quote, which is truly striking: “They [human lives] are composed like music… Without realizing it, the individual composes his life according to the laws of beauty even in times of greatest distress. It is wrong, then, to chide the novel[ist] for being fascinated by mysterious coincidences… it is right to chide man for being blind to such coincidences in his daily life. For he thereby deprives his life a dimension of beauty.”
Ah, a fellow Kundera fan!
But please, go on. What made you decide to join?
I did not know much about this topic and was not sure where we could go with it. So I agreed to perform a review of the literature on Alzheimer’s, to see what was there and to educate myself, and then decide what to do with the idea of the organization.
This review work, which took two years and was performed with an amazing group of international collaborators, was for me the beginning of WBP. It resulted in a publication in Nature, “Sex differences in Alzheimer disease — the gateway to precision medicine”, but it meant much more than that.
First of all, it allowed us to create a network of colleagues, scientists, and supporters, who helped us in the process and are still nowadays working with us.
Second, it changed the way I looked at the issue and crystallized in my mind some key concepts that I tried to bring to WBP. It made it clear for me that there are a lot of important differences in the way the disease presents itself, progresses, and even responds to treatment between men and women (well beyond the ‘more women than men’ issue).
We are not doing anybody a favor with the one-size-fits-all approach. By grouping men and women together, we are offering everybody a less than optimal treatment, instead of a tailored one. The importance of precision medicine, and its relevance for both men and women, became very clear to me and went into the heart of WBP’s activities.
What work (or life) experience brought you personally to view women as requiring a better-adapted/more finely tailored approach to medical treatment, in particular for Alzheimer’s?
MTF: The scientific evidence that I gathered while writing the review, and then in later studies, convinced me that brain pathologies are complex and patients heterogeneous.
Sex differences are robust, for instance in cognitive scales and in biomarkers. What if women are diagnosed too late in the disease because they outperform men in the test of verbal memory? What if some treatment of ‘failed’ clinical trials were actually benefitting one sex? What if we could come up with better diagnostics and therapeutics, just by considering sex differences? These thoughts really motivated me.
Beyond this professional experience, I must say that I had in my close circle of friends several cases of depression, all affecting women (2/3 of patients suffering from depression and anxiety are women); in many cases, severe socio-economic problems were causing it, conditions ingrained in the status of woman in the family and society, in one word, gender. I just saw it clearly, as soon as I started to work on this topic, and felt even more compelled to do something about it – to find specific ways to support women.
Finally, my personal experience with breast cancer made me aware of the power of precision medicine on one hand (as oncology is much more advanced in this than neurology). On the other hand, it made me realize the plethora of female-specific risk factors to brain diseases. Here is my TED talk on this (it’s in Italian, December 2019):
I found your TED talk fascinating. You are essentially calling for radical change in the treatment of Alzheimer’s and neurological diseases along the lines of what happened in oncology with the advent of “precision medicine”. Precision medicine means taking into account both sex differences and individual differences in a patient’s reactions to treatment. It requires much closer observation of patients and a deeper understanding of their past history. Can you illustrate this to our readers?
Precision medicine is the opposite of shallow medicine, to quote Eric Topol. In shallow medicine, we assume that an average patient exists, and we design treatments and diagnostics based on the average measurements taken from thousands of patients. It turns out, the average patient does not exist. The same treatment can be very effective in one patient but ineffective in another.
In oncology, we now know that there is not such a thing as ‘breast cancers’, but several subtypes have been identified. Not all of them respond to the same treatment. It is now possible to characterize at the molecular level the type of cancer that a given patient has; this allows us to identify the appropriate treatment for that patient. We can also (as it happened to me) analyze a series of genetic markers to predict the response to chemotherapy, and further tailor cancer management in breast cancer patients, also avoiding side effects.
In neurology and psychiatry, we are far away from this point. A symptom, such as cognitive decline, can be due to a plethora of reasons (from depression to infection), and we have still a very hard time identifying the causes of brain and mental diseases. This translates into very imprecise ways to treat them, largely based on trial and error.
When it comes to sex and brain diseases, there are a lot of aspects that could help us making diagnosis and treatment better for patients. For instance, being aware of sex-specific risk factors could help to tailor preventative strategies. Early menopause brought about by ovariectomy, which is needed in many cases of female cancers, is a risk factor for cognitive decline. Most breast cancer patients experience depression, possibly due to their treatments. Nobody talks about this and yet they are so common; I really think women (as well as men) deserve to be informed of the latest science and know their specific risks, to act on them and be prepared.
I agree, far more information is needed to be able to fine-tune treatment and meet everyone’s needs. Let me ask you a question about WBP’s history. When it was launched in 2016, what were the initial problems, how did you overcome them?
MTF: We have been blessed I think, as our initiative was likely the right thing at the right time. With the rise of the #metoo movement, a lot of awareness was growing towards women-specific issues.
However, we all experienced resistance to the ideas we were proposing at the beginning. We have been asked ‘Is this (i.e. adjusting drug development to sex) really needed?’, or ‘are there really differences between men and women?’
Academia is a bit slow to take up new ideas, but we created momentum and simply went ahead, with papers, producing evidence and stimulating a debate on the topic that was picked up by our colleagues, with a snowball effect. We are very proud to see the huge improvement in the field since 2016 – we are sure WBP contributed to it.
WBP is now four years old, what have been your greatest successes?
MTF: Right now sex and gender research are becoming mainstream in Alzheimer’s, and I really think our work has had a huge effect on this. We have published several landmark papers in prestigious journals including Nature and PNAS, and we are writing the first academic book on the topic with Elsevier.
To illustrate this further: In this paper, we described sex differences in Alzheimer’s and explained why they are relevant for clinical practice; this was an important work as it was done in collaboration with the dementia panel of the EAN and has been officially endorsed by the organization. In our latest article, we provided for the first time a comprehensive overview of sex and gender bias and their relevance for the development of digital tools for health.
We have organized several international Forums, the first in 2017 with four panels and 20 speakers, the second in 2019 with 8 panels and about 40 speakers, attended by 130 participants from all over the world, which have become a reference point for experts in the field. The latest Forum in 2019 even featured the advanced humanoid Sofia, with whom we discussed gender bias in artificial intelligence (AI):
The upcoming Forum will take place virtually on 19-20 September and is now open for registration.
We have brought this topic to the lay public with some key interviews, especially the one with BBC Future in 2018 exploring why Alzheimer’s hits women harder than men. Finally, the acknowledgment of Antonella as Woman of the Year in Business in Switzerland in 2019 was for us the proof of the importance of our work.
All this was achieved with a nonprofit organization in which people work pro bono – the passion of our team and supporters is our greatest success.
Looking to the future, what are your plans and your hopes for WBP?
MTF: In the short term, we are very excited by our next forum, which will be a spectacular event featuring regulators, scientists, drug developers, and patients and caregivers.
Highlights of the Forum will include an opening given by the European Commissioner for Research, Youth and Innovation Mariya Gabriel and talks by Dr. Kaveeta Vasisht from the US Food and Drug Administration (FDA) Women’s Office, Dr. Neerja Chowdhary from the World Health Organization (WHO), Dr. Lisa Mosconi from Weill Cornell Medical College in New York, Dr. Louise Howard from King’s College London, and Dr. Londa Schiebiger from Gendered Innovations.
During the Forum we will officially launch the Swiss edition of the Be Brain Powerful Campaign, which will be run by WBP in collaboration with UsagianstAlzheimer and we will announce the results of the first hackathon on the topic of sex differences in biomedical data.
That’s a remarkable gathering and an amazing hackathon!
MTF: In the long run, our dream is to create a research institute focused on sex and gender differences for precision medicine. We are starting to collect sponsors and investors for this, and we need all possible help. Our goal, and hope for the future, is to change the way we do medicine, and especially drug development and novel technologies, for the benefit of both men and women.
In the Featured Image: Forum Ambassador Fagun Thakrar interviewing Sophia the Humanoid Robot (2019 Forum) Source: WBP