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Reimagining treatment for brain diseases to improve the lives of patients and their families: Ana Raquel Santa Maria

Seeing her own grandparents’ health decline through the years, Technology Development Fellow Ana Raquel Santa Maria was inspired to have a positive impact on patients and their loved ones

By Jessica Leff

Listen to Ana tell her story. | Wyss Institute · Ana Raquel Santa Maria Reimagine The World
Reimagining treatment for brain diseases to improve the lives of patients and their families: Ana Raquel Santa Maria
Reimagining treatment for brain diseases to improve the lives of patients and their families: Ana Raquel Santa Maria
Ana Raquel Santa Maria is inspired to Reimagine the World with better understanding, prevention, and treatment of brain diseases after seeing her grandparents suffer as they age, especially her grandmother who has dementia. Credit: Wyss Institute at Harvard University

Situated in the eastern part of Beja, the second-most southern District of Portugal, Moura is a small, historic village with a dry climate, surrounded by a countryside full of oaks and olive trees. It’s where Ana Raquel Santa Maria, Ph.D, grew up with her mother, father, and younger brother.

Family has always been a central part of Ana’s life. She spent her summers in the big city, Lisbon, with her father’s parents, visiting science museums and enjoying parks with her grandfather. When she was six years old, her family moved to a house across the street from her mother’s mother, which proved useful when she was in high school and needed to get serious studying done. Free from her little brother and her six younger cousins, she could concentrate on her homework and enjoy her grandma’s cooking.

The birth of a scientist through books

Even before Ana could read, she would sit in her living room staring at the bookshelves. There were some larger ones that always caught her eye, so one day she decided to try and pick them up. Instead of immediately dismissing her interest or insisting she was too young, her father said, “I don’t know if you’ll understand this, but let’s open it up and see.”

Reimagining treatment for brain diseases to improve the lives of patients and their families: Ana Raquel Santa Maria
Even before she could read, Ana’s father’s science textbooks piqued her interest. Credit: Ana Raquel Santa Maria

Maybe he was so encouraging because these were his old science textbooks. “I remember those books so well,” Ana says. “There was chemistry with lots of interesting figures, mathematics, and physics. I told myself, one day I will understand what is written here.”

When she was around four years old, Ana became interested in some newer books on the shelf that came as a gift from her grandfather. “They were white and had some green on the cover,” Ana recalls, “What I remember most about them was that new book smell. I still love that smell! Even not knowing how to read them, I was looking at the pictures, making my own stories.” These books were also science-related – they were full of simple experiments for children. “Once I knew how, these were the first books I went to read.” Though she did not understand the reason behind the activities, this was one of the first times Ana was exposed to the scientific method.

As soon as she could read, the whole world opened up for Ana. When she didn’t know the answer to a question at school, she searched for it herself, always wanting to know more. “I think that’s the beginning of a scientist there,” she reflects.

A desire to make the world a better place

Reimagining treatment for brain diseases to improve the lives of patients and their families: Ana Raquel Santa Maria
Ana dressed as a nurse when she visited her grandmother, who was diagnosed with osteoporosis and later with dementia, in the hospital. Credit: Ana Raquel Santa Maria

Around the same time Ana’s family moved, her grandma was diagnosed with osteoporosis. Trying anything she could think of to help, Ana went to visit her grandmother dressed as a nurse. She wore a white paper hat with a red cross on it, a white dress, and white tights. Her grandmother loved it, telling everyone, “My nurse is taking care of me!”

Seeing “patients” up close had a huge effect on Ana. “In the car on the way home, I said to my mother and father, ‘I want to change the world. I want to make the lives of these people in the hospital better.’ I didn’t know exactly how at that time, but that started me on that path.”

Then, as Ana got older, she began to notice a pattern. Her father’s father, the one who lived in Lisbon that she was very close with, had always struggled with diabetes. He eventually developed a heart condition and passed away from heart failure. Ana says, “I noticed that as people age, they have more and more health problems. I wondered what we could do to change this and give them a better life.”

When the castle’s defenses are breached

Though Ana knew she wanted to have a positive impact on the world, she wasn’t sure how to do it. Then, her biology class started studying the central nervous system, including the brain. Ana recalls, “I was amazed by this complex organ where there are so many things going on that we don’t understand. During that time, it clicked. I said, ‘This is what I want to do. I want to change the lives of people when they get older by working on the brain.’”

Now, Ana describes the brain as a castle surrounded by several guards, or barriers; most notably, the blood-brain barrier. Although scientists believe they know the structure of the brain, or the blueprints of the castle, it’s very hard to get into it because of these barriers. So, it is essential that researchers study these barriers to understand them and find mechanisms to use to our advantage to find a way into the brain to treat neurodegenerative diseases.

A day to remember

Two years ago, just after Ana moved to the United States to began working at the Wyss Institute, her grandmother, whose home had provided a warm space for studying early in her scientific journey, was diagnosed with dementia. Ana recalls, “In the first year it was fine, she could still do her normal routine and be independent. That has changed very fast.”

Reimagining treatment for brain diseases to improve the lives of patients and their families: Ana Raquel Santa Maria
Ana, her husband Viktor, and her grandmother on her wedding day. Credit: Ana Raquel Santa Maria

In September 2022, Ana returned home to celebrate her wedding with a beautiful ceremony back in Moura that combined her Portuguese traditions and her husband’s Hungarian ones. They were surrounded by friends and family from around the world. This joyful day also has the distinction of being the last time Ana’s grandmother knew who her granddaughter was.

“I went over to her, because she cannot move much on her own, and she grabbed my hand and said, ‘oh my little doll!’ Then we put our foreheads together while still holding on to each other’s hands.” Ana remembers. Because of her grandmother’s declining health, she left the reception before it was over. Ana was still dancing, but her grandma pulled her aside and said, “Behave well my doctor, see you tomorrow.”

Recently, Ana returned to Portugal and saw her grandmother again and was met with an empty stare. “To sit next to her, to hold her hand, but know that the person who was playing with me and spent so much time with me doesn’t know who I am and is not there is the most difficult part. It’s hard to see your grandmother doesn’t recognize you anymore.”

“It’s so hard to say goodbye now,” Ana adds, “because she’s in Portugal and I had to return to the United States. I don’t know if each goodbye is going to be forever. My grandmother doesn’t remember, so to her it’s just another time, another day – maybe she doesn’t even recognize the days anymore. But for me, it’s one of the trips where I cried the most.”

Breaking barriers with The Brain Targeting Program to help future generations

If Ana could Reimagine the World, it would be one with better understanding, prevention, and treatment of brain diseases like dementia and neurodegenerative disorders to improve the lives of patients and their families. She knows all too well the toll these diseases take not only on those who have them, but on their loved ones, who are often left without the support or skills they need to care for someone close to them. Ana explains, “Nobody tells you how to take care of your mom or dad that does not remember you anymore.”

Reimagining treatment for brain diseases to improve the lives of patients and their families: Ana Raquel Santa Maria
The Brain Targeting Program team at the Wyss Retreat in 2022. Ana is in the back row, third from the left. Credit: Wyss Institute at Harvard University

At the Wyss Institute, Ana is a Technology Development Fellow and part of the Brain Targeting Program, where she’s making her vision a reality by working to discover proteins that are expressed in the blood-brain barrier and could transport therapeutics to the brain. Currently less than 1% of drugs taken orally enter the brain from the bloodstream, which is one of the main challenges in treating brain diseases. By identifying existing transport proteins, Ana and her colleagues are using the body’s own mechanism to deliver therapies where they need to go.

The Brain Targeting Program is organized as an R&D hub to promote collaboration among diverse stakeholders, including competing companies and academic labs. Its first pre-competitive project supported discovery of brain-targeting shuttles that can benefit all participants’ drug programs while advancing the entire field.  Ana says, “The Wyss is a unique environment to develop this project. I don’t think it could be done anywhere else.”

Ana did eventually read her father’s textbooks. Though they weren’t exactly the topics she studied in school, her curiosity and determination won out, and she wanted to see if the information could be useful. In fact, she still has them. “Those books will stay with me forever and be passed through generations for sure.”

And though her grandmother won’t directly benefit from her work at the Wyss, Ana hopes her family’s experience and legacy will help people in the future, “If I can change the life of one person and one family, mission accomplished. That’s what motivates me day by day, to give people with these diseases and their families a better life.”


Brain disease diagnosis with medical doctor diagnosing elderly ageing patient neurodegenerative illness problem seeing Magnetic Resonance Imaging (MRI) film for neurological medical treatment

Help us cross the ultimate barrier to new brain disease treatments

Alzheimer’s disease, Parkinson’s disease, brain cancers, and rare genetic disorders of the brain all share one common challenge: they lack effective therapies in major part because drugs cannot cross the blood brain barrier. The Wyss Institute’s Brain Targeting Program is focused on dramatically improving discovery and development of technologies to deliver drugs specifically to the brain to improve outcomes for the millions of patients suffering with neurological diseases. Get in touch today to learn how you can help us cross the ultimate barrier to improve brain disease treatments.

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