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HD InsightsNo Power in Victimhood

Tacie Fox, an engineer, businesswoman, and mother of two sons, is a central figure in the Huntington’s disease community today. When her family came to understand that they were carriers of the HD gene, she gave up her job in investment banking and became a warrior in the search for treatment and a cure. Her HD story begins when her father, G. William Fox, learned that his mother’s neurodegenerative disease had a name, and that he was at risk for having HD.

Bill Fox, trailblazer

When Bill Fox became symptomatic with HD, he was 50 years old, and the owner and CEO of the largest residential real estate brokerage company in the Philadelphia tri-state area. He was in his prime, and poised to manage and grow this 100-year-old family business for the next several decades and then pass it on to his children.

With HD, that all changed, and by the time he was 60 he was unable to run the business and needed to sell it in order to have money for his medical care and to help support his family after his death.

My father was a gifted athlete and as his symptoms progressed, he could no longer do many of the things he loved, especially skiing and swimming in the ocean with his children and grandchildren. After he had given up his last sport, golf, I asked him if it was really hard to not be able to do so many things he’s enjoyed his whole life because of HD. He cocked his head sideways as he thought about it and said, “I guess I am just grateful for the things I still CAN do.”

I thought, WOW, now that’s the way to look at life as you age or develop a disability! He gave me such a gift of perspective in that moment. Carpe Diem — really — don’t sit around thinking you should do it, just do it! Live with a purpose. Be grateful for what you have and what you still can do, even if you did more at an earlier point in your life.

Bill had a brother and two sisters. One sister, Mary, had HD, aligning the family along the expected toss-of-the-dice odds. Mary developed HD symptoms at 40, ten years earlier than Bill did, and died before he did.

When Bill became symptomatic, he broke with convention and sent a letter to his 500 employees and agents telling them he had HD.

HD was something my father’s family didn’t talk about throughout my grandmother’s decline. It was almost verboten. My parents decided that it was important to change that for our family.

Bill then became a spokesperson for HD and actively engaged in fundraisers to support research and families with HD, through the Hereditary Disease Foundation and the Huntington Disease Society of America. He founded the G. William Corporate Humanitarian Awards, and along with his wife Sandy, formed the Fox Family Foundation to help fund HD research in a race for a treatment that would cure the disease before it manifested in their children, nieces and nephews.

Stronger Than the Thief in the Night

Sandy Fox’s response to her husband’s illness was to concentrate her energies and lifelong winning attitude to supporting these initiatives. She expressed some of these thoughts on Fox family videos that became part of the G. William Fox humanitarian award events. She and her husband Bill had a wonderful love affair and were a united team.

We found parts of ourselves that we never knew were there because we hadn’t needed them before.

Huntington’s is the thief in the night that comes in silently and stealthily steals precious aspects of life. But over the course of our time together I’ve come to know another aspect of Huntington’s, which is that it is a great teacher about what’s really important in life and that is to love and find joy in every day.

Sandy refused to be defeated by the disease even after Bill’s death.

My mother is a very strong woman. After my father died, we were sitting at the kitchen table when she turned history around. I’ll never forget that vision of my mother making a fist and saying ‘I’ve got to do something about this. I don’t know what I’m going to do, but I am going to do something about this.’

Sandy went on to join the Board of Directors of the Hereditary Disease Foundation under the leadership of Nancy Wexler. She and Tacie doubled down their mission to support finding a treatment. They flew around the country meeting with scientists on a crash course to learn about the latest research and select research projects to fund through their foundation.

In a family with HD, one hour with the researchers puts you back in the game with renewed hope, vigor and resolve to make a difference.

Tacie takes up the mantle

This was the start of their working hand-in-hand to understand the disease, the research and what their role might be in working toward a treatment and cure.

A Duke engineering graduate who later earned an MBA from Wharton, Tacie had been on a fast track in the business world when the news came about her father. With Sandy’s inspiration and encouragement, Tacie and her Aunt Mary’s daughter Jane, with whom Tacie had been inseparable from birth, decided to take on HD by force, learning everything they could. Jane was a pharmacist and quickly assimilated technical medical information. They were a dynamic duo attending yearly scientific conferences together, starting in 1993 and forged lasting relationships with many in the HD research community.

Tacie’s Testing Decision

Neither Tacie nor Jane were symptomatic through those early years, but Jane needed to know if she had the gene and she decided to get tested. She was devastated to learn that she tested positive.

This was a time bomb that dramatically impacted all three generations of my family, and it tore me apart. Now HD was in the next generation, my generation, and I would go on to lose my best friend, watching her struggle, without being able to slow down her decline.

This began a profound journey of grief for Tacie, but with the added motivation of helping Jane, she redoubled her efforts to understand the science and support researchers in finding treatments. Jane, however, could not continue by her side as her disease progressed.

Tacie had long ago decided that testing was not the best course for her, as long as she remained asymptomatic.

I decided not to get tested because I felt I could continue to be a glass-half-full person with a 50% risk of HD much easier than I could with 100% certainty of having HD. I thought if I tested positive that could be paralyzing, and I could well turn into a glass-half-empty person and lose both my motivation to be strong for my family members and my determination to make a positive impact in HD.

She is now 61, and a decade or more older than any of her family members when they first manifested. She went through fetal testing twice, with none other than gene-hunter Nancy Wexler by her side, who became a very dear friend to the entire Fox family and a mentor to both Tacie and her son Nick.  

More Family Members Become Symptomatic

Another bomb dropped on the family when Tacie’s youngest sister, Sara, became symptomatic at just 41 years old.

When my little sister developed symptoms, my heart was torn apart! A few years later another cousin with whom I was close was diagnosed. We urgently need to find a treatment for HD now, while it can still benefit them!

Sara still goes to her daughter’s lacrosse and hockey games, but even though she is a trained chef, she’s had
to give up her passion for cooking. Now her husband Tom does the shopping and cooking for the family.

Sara has participated in three trials, including the PROOF-HD trial for pridopidine.

It has been a gift to me to accompany my sister to her drug trial visits and given me a deep respect for those participating in trials and boundless appreciation for the clinicians that treat HD patients.

My sister and cousins with HD are so brave. Their positive attitude and steadfastness motivate all of us and increases our dedication and sense of urgency to help — for their sake and for their children.

Pursuing an “HD PhD”

Tacie refers to herself as a PhD wannabe — a lay person who continually reads to the end of countless scientific papers, digging for understanding.

Like her mother, she is a board member of the Hereditary Disease Foundation, and is excited that she has been able to attend their research symposiums, intended for scientists only. She also attends the highly scientific CHDI conferences and Huntington Study Group annual meetings.

Her thirst for knowledge of the disease, its mechanism of action, and possible treatment targets is relentless.

Fox Family Foundation Grants

Tacie heads up the Fox Family Foundation, which each year picks a research project to support financially. They awarded many grants through the Hereditary Disease Foundation (HDF). The family’s relationship with HDF started before the gene was discovered in 1993, and the family forged a friendship with Nancy Wexler as she and her team of gene hunters were making history.

Early Fox grants went to fund collaborative research workshops with bright young scientists newly working on HD, many of whom are leaders in the scientific community now. When Bill died and Sara and her cousins became symptomatic, the Foxes decided to focus on the grants that they felt had real potential of a near-term therapeutic benefit for those in Tacie’s generation.

We have looked for novel activities that may be able to interfere in the disease process to really make a difference in people’s lives. Now, we are focused on supporting a quest for a treatment that helps delay or slow onset for my sister, my cousins and their children.

When Nancy Wexler became symptomatic, the Fox family was stricken.

What a cruel act of fate — Nancy Wexler, the person who arguably had done the most for HD research — fell victim to the disease before a cure could be discovered.

In honor of Nancy, the Foxes have doubled the number of HDF grants they funded in the last two years.

Last year’s grants went to Bev Davidson’s lab at Children’s Hospital of Philadelphia to evaluate the brain penetration potential of a newly developed AAV. With the Fox grants, Dr. Davidson’s team proved that their AAV was able to deliver drugs into the deepest regions of non-human primates. The next step is to replicate this in humans.

This year’s grants went to Christopher Pearson’s lab at Hospital for Sick Kids in Toronto to fund two different research projects involving somatic expansion.

In certain brain regions and organs of HD patients, the length of their CAG repeat continues to expand as they get older, a phenomenon known as somatic expansion. The hypothesis is that onset of HD symptoms occurs when the number of repeats grows or expands significantly in a high concentration of neurons. So, it isn’t the fact that a person has above 40 repeats that causes HD, it’s that those repeats are growing to 75 or 100 that triggers symptom onset.

Dr. Pearson’s lab is evaluating a molecule that they believe will keep these expansions from growing out of control. Tacie’s hope is that this new AAV could deliver this somatic expansion-slowing molecule to delay onset of HD symptoms and slow down disease progression.

So many of the things that we’re finding out in terms of research are going to be treatments that will delay the onset of the disease. These are not all going to lead towards the cure, but they’re very, very powerful approaches in and of themselves.

Huntington Study Group Connection

The Fox family met Ira Shoulson shortly after he founded the Huntington Study Group, and he became a close family friend. As Bill progressed, Ira and he bonded.

The way he interacted with my father was incredible. He was compassionate, loving, funny, with a deep understanding of what my father was going through.

The Fox Family Foundation has been a sponsor of the annual HSG conference for almost 20 years to help pay for clinicians and coordinators who don’t have institutional financing to attend the annual meeting. The family is also helping to fund the new initiative, HD-ENGAGE, to bring more neurologists into the HD fold.

It is so important to support the HSG conferences because they are an essential forum for clinicians to learn, train, brainstorm and collaborate on new innovative research and clinical care.

HSG has evolved into a premier platform to run drug trials while maintaining their core mission of capable, consistent and compassionate care of HD patients. Ira told me ten years ago that his goal was that HSG would run one new HD trial a year. Bravo! HSG is doing that!

HSG appointed Tacie to serve as the patient advocacy representative on two different drug trial steering committees, where she worked closely with Jody Goldstein, Karen Anderson, Julie Stout, Andy Feigin, and Elise Kayson, among others.

During this time, Tacie became intimately familiar with the hopes and the frustrations inherent in getting drugs to trial and to approval. One of the key things that she learned is that a trial’s success is greatly dependent on the endpoints selected, and the FDA does not permit a number of important and measurable biomarkers to be primary endpoints.

In one of the trials, Tacie learned that the FDA will fail a drug trial if symptomatic improvement is not yet evident, even if objective imaging shows slowing of brain shrinkage. She is frustrated that the FDA will not recognize these as a primary endpoint in a drug trial because a relationship between reduced brain shrinkage and symptomatic improvement has not yet been established in HD.

If a treatment helps protect the brain, even if it does not result in symptomatic improvement, isn’t that worth doing, especially since there is no other option right now? If treatments are available that can preserve brain volume, patients may stay eligible for trials for longer. In spite of these frustrations, thankfully, HSG continues to lead the charge with the FDA to approve new biomarkers.

Warriors for Life

Tacie’s sons, Alex (24) and Nick (22) have upheld the Fox family tradition of strength and an all-in devotion to what needs to be done.

Both of my sons were close to my father and are champions of my sister and cousins in their battles with HD now. When my sister comes to stay with us the night before her PROOF-HD trial visit, Nick cooks dinner on the grill for his Aunt Sara, and the next morning Alex makes Sara her favorite omelet for breakfast.

Alex, who had a brain tumor at two years old and wasn’t expected to recover cognitively from his surgery, fully recovered, became an accomplished competitive chess player and is now a mechanical engineer with AECOM.

Nick dove into the HD world as a young teen, attending HSG conferences with his mother.

At the 2018 HSG conference, Nick got his first introduction to the HD clinicians and scientific community. He met many scientists, and listened to them explaining their posters and research and was fascinated by their findings. He was hooked! That is when he decided he wanted to be a scientist.

He would go on to work with Diana Rosas at Mass General in high school and later shadow Karen Anderson, his Aunt Sara’s clinician. In college, Nick did research using HD human fibroblasts in Andrew Yoo’s lab at Washington University in St. Louis, where Nick just graduated with a bachelor’s degree in psychological brain sciences: cognitive neuroscience. At 22, he is working at the NIH National Institute of Neurological Disorders and Stroke, with aspirations of getting a PhD and doing HD research.

I am so proud of both Alex and Nick! Alex and I are cut from the same mold and can relate on a deep level. Nick and I have a special bond learning about HD research together. I love going to conferences with him and seeing Nick engage with scientists. He became a trustee of our foundation and collaborates with me and my mother to evaluate grant opportunities. Together we are trying to puzzle out the latest exciting research that will change the course of the disease. It is exciting to our family that his passion is for the very science we as a family desperately need.

HD Angels

Tacie says what inspires her the most and has kept her from the dreaded fear of the ticking clock for all her family who are at risk or gene positive has been the scientists and clinicians.

It is hard to describe the feeling of being in a room with so many brilliant people talking about the intricacies of new HD research breakthroughs, seemingly at the sub-atomic level. While I take notes furiously, desperately trying to understand their highly technical presentations, the energy and excitement amongst them is pulsing through the room as they listen to colleagues talk about their latest research that unravels another piece of the puzzle. I am riveted on their every word, knowing that they collectively hold the life-or-death card for my family members and the HD community at large.

I get choked up thinking about the difference Sara’s clinician, Karen Anderson, has made in her life and mine. I know that to be true with so many other clinicians I’ve met through HSG. These are rare, gifted leaders and wonderful people, and I am so lucky to be part of their community. Knowing with confidence that all these HD leaders are at the helm and learning about each promising discovery is what motivates me to keep fighting for all those I love who face this tragic disease.

About HD Insights

Our mission is to promote, disseminate, and facilitate research on Huntington’s disease. To fulfill this mission, we are guided by an outstanding editorial board that includes representatives from three continents, academia, industry, and the HD community.