It is with a very heavy heart that my wife and I would like to inform you of the passing of our son, The POLG Foundation Founder and Creative Director, Frederik.

Last Friday, February 28th, on “Rare Disease Day”, our beloved son called us in to his room to speak to him for one last time. Frederik found the strength and the courage to say goodbye to each of us in turn – his brother, Alexander; his sister, Charlotte; me; his three cousins, Charly, Louis, and Donall; his brother-in-law, Mansour; and finally, his Aunt Charlotte and Uncle Mark. He had already spoken all that was in his heart to his extraordinary mother, who had not left his side in 15 years. After gifting each of us with our farewells – some kind, some wise, some instructive – in true Frederik fashion, he left us collectively with a final long-standing family joke. Even in his last moments, his humour, and his boundless compassion, compelled him to leave us with one last laugh….to cheer us all up.

Frederik’s last question to me, prior to his other remarks was: “Papa, are you proud of me?” He had barely been able to speak for several days, so the clarity of these words was as surprising as the weight of the moment was profound. The answer was very easy, and he had heard it oh so many times…. but at this time, he needed reassurance that he had contributed all that he possibly could in his short and beautiful existence and that he could now finally move on.

Frederik knows that he is my Superhero, as he is to all of our family, and to so very many good friends and now in great part thanks to his POLG Foundation, to so very many people the world over. Part of his superpower was his ability to inspire and to lead by example. Frederik was born with a special capacity for positivity, joy, and determination. When he was little, I would always say that if there is one child of ours that I would never need to worry about, it was him. He has social skills like no other, an amazing sense of humour, an emotional intelligence and compassion that were off the charts, a sense of justice, fairness and decency that knows no bounds. He was disciplined and organised beyond belief. On Friday, his Italian Duolingo and exercise alarm went off like any other day…. but this was not any normal day. This would be his last in this world….and Rare Disease Day, a day that was created in order to raise awareness and generate change for people living with one of these orphan illnesses and of course for their families and precious caregivers.

As his siblings and most anyone who ever met him say, "Frederik is the strongest person that we know!" Frederik fought his disease valiantly until the very end. His indomitable lust for life propelled him through the hardest of physical and mental challenges. Our cheery Frederik saw the beauty in everything. His brother Alexander recounts that, while Frederik was recently hospitalized battling pneumonia and another serious infection and unable to move or take photographs himself, he asked Alexander to capture the setting sun. Alexander, understandably influenced by the dire circumstances, found the view of the rooftops bathed in a warm glow, rather bleak. But to Frederik, it was magic! Through the small, mesh-covered window, he saw the Eiffel Tower glistening with its hourly dance of lights. He found it so beautiful that he wished to share it with all of his friends. Charlotte reminds me that the sun has shone every day since Frederik's passing, pouring into the room and warming the bed where he last lay. On his phone, he kept many sage reminders to self, one of which read, "Go outside when the sun is shining." We will strive to follow his instructions, especially now that everything feels a little colder and darker in his absence.

Although we did not know this, at the time of his birth, Frederik was born with a Rare Disease; POLG Mitochondrial disease. As is the case for 300 million people like Frederik worldwide, these diseases are usually hard to recognise even by physicians, and patients’ families may never know what they are suffering from as they may only be identified very late in their progression. Frederik was diagnosed with POLG at the age of 14, when his symptoms were showing more clearly and when the progression of his disease had become more acute. Because POLG disease causes such a wide range of symptoms and affects so many different organ systems, it is very difficult to diagnose and has no treatments much less a cure. POLG disease is a genetic mitochondrial disorder that robs the body’s cells of energy, in turn causing progressive multiple organ (brain, nerves, liver, intestines, muscles, swallowing and ocular function, etc.) dysfunction and failure. One might compare it to having a faulty battery that never fully recharges, is in a constant state of depletion and eventually loses power.

Frederik is particularly headstrong (at times, I might have used the word stubborn). This serves him well. I cite him as being here in the present because I know that, though physically absent, he is still here, inspiring us and pushing us forward. His mission is not complete, and we all have much work left to do. Frederik and The POLG Foundation, along with our extraordinary Board of Directors and Scientific Advisory Board, are committed to finding therapies and a cure to save other patients from suffering what Frederik and our family have endured. To quote Sir Douglas Turnbull, an eminent professor and member of The POLG Foundation Scientific Advisory Board:

“I have looked after literally hundreds of patients with mitochondrial disease and there is little doubt that of all mitochondrial diseases, POLG deficiency is the worst. It is so relentlessly progressive, attacking so many different systems with sadly the same conclusion.”

This is the battle that Frederik fought, and this is the burden that he had to carry throughout his life. He always did so with grace and with humour. When we asked him if he wanted to create a foundation to find a cure and help others like him, he jumped at the opportunity. Though he always made it very clear that he did not want this dreadful disease to define him, he nonetheless immediately identified with and helped define the mission of The POLG Foundation. Here, Frederik put his significant creative talents to work. Working with our friend, Willa Shalit, and her talented team, he created the look and logos for our new 501(c)(3) nonprofit U.S. public charity, which was born in 2022. After the website was created, he focused his creativity and humour on launching the MITO clothing line, which found an alternative way to spread awareness through the sale of cool, amusing and at times irreverent t-shirts, baseball hats, beanies, and hoodies. Frederik was encouraged by other designers, including his friend Donna Karan.

Frederik was also keen to help the science move forward. He actively and literally gave of himself to develop multiple mouse models and cell lines in Switzerland, the United States, and Europe and to make these available to further facilitate research into POLG. These elements became the foundation of our POLG Tool Box, which continues to grow by the day. Frederik also participated in medical trials with the goal of finding treatments and, perhaps, ways of repurposing molecules to help patients with his condition.

Although she would never want to take credit, his mother, Julie, is the driving force behind these efforts, working indefatigably for 15 years not only to care for Frederik but also, in the past few years, to unite the global scientific community in a sense of urgency and collaboration to change the tragic perceived outcomes of patients that Professor Turnbull describes above. Beyond this tireless work, his mother attended, organized, and animated conferences globally to encourage advancement and collaboration in POLG research. ^*1

Though recently created, the nascent The POLG Foundation, in only 3 short years, has accomplished so very much:

1. We have created our Toolbox. From Frederik’s DNA, we have generated sequences and induced pluripotent stem cells or IPSCs (https://neurocenter-unige.ch/research-groups/denis-jabaudon/ and transgenic mice (Jackson Laboratories https://www.jax.org/, University of Padua https://cesne.biologia.unipd.it/research-groups/carlo-viscomi/). These precious tools are available for researchers globally to help accelerate development of specific treatments and cures for POLG disease.
2. We have funded four major research projects, totaling over $3.6 million USD. These projects have resulted in publications in peer-reviewed, high-impact journals. Since the Foundation's inception, we have seen a substantial increase in POLG research activity. Read those articles here.
3. Working with other Mitochondrial Advocacy Organizations (e.g. Lily Foundation, UMDF and Mito Foundation of Australia) we have partnered on development of a clinical trials readiness tool called Casimir for Digital Video Assessments (DVA). We also have embarked on a Project Butterfly at Columbia University for studying invaluable post-mortem tissues from 2 POLG families who have made such courageous donations to advance POLG research.
4. In 2025, we are launching the first ever international prospective POLG Natural History study^*2 to pull the POLG community together and enable key clinical data collection to help inform better clinical care and efficient clinical trial design for drug development. We anticipate that this body of work and datasets will be considered the ultimate tool in our Toolbox for the broader global biomedical community.
5. Frederik's Fashion creations can be found at our online shop here.
6. In order to aid with awareness, Frederik and his mother created a film that tells the story of the disease from the point of view of Frederik and other patients, while featuring some of the greatest mitochondria experts.
   PolG Film Link
7. In 2025, we will begin working on a animated Cartoon education series to educate physicians and the general public about POLG.

The Broader Impact of POLG Research:

Research into POLG-related disorders holds significant potential beyond just these specific conditions. Because mitochondria are essential cellular organelles, the understanding how POLG mutations disrupt mitochondrial DNA could illuminate pathways relevant to a wide range of diseases and even human ageing.

Potential Benefits:

Other Mitochondrial Diseases: Insights gained from POLG research could be applied to other mitochondrial disorders with similar mitochondrial DNA dysfunction, including how external factors (e.g. viruses, bacteria, environment) can affect the course of the disease.

Infectious, immunologic conditions and susceptibility to viral pathogens

New research by Prof. Suomalainen suggests that POLG1 defects compromise antiviral tolerance, triggering epilepsy and liver disease. The finding has important implications for the mitochondrial disease spectrum, including epilepsy, ataxia and parkinsonism.

Neurodegenerative Diseases:

POLG-related neurological symptoms may offer clues to diseases like Parkinson's and Alzheimer's, where mitochondrial involvement is increasingly recognized.
Specifically, POLG research could unveil ways to protect motor neurons in ALS and restore mitochondrial health in Parkinson's.

Cancer:

In pancreatic cancers, POLG has been highlighted as a novel prognostic marker and inhibition of POLG may enhance anti-cancer therapeutics.

Mental Health:

Emerging research links mitochondrial dysfunction to mental health disorders like depression and mania. POLG studies may reveal how mitochondria affect brain function and mood, leading to new therapies.

Age-Related Diseases:

As mitochondrial function declines with age, POLG research could identify mechanisms to maintain or restore mitochondrial health, potentially delaying or preventing age-related diseases.

Human Ageing:

By addressing mitochondrial dysfunction, we may be able to slow cellular ageing, improve health span, and potentially increase longevity.

In essence, POLG research is about understanding the fundamental role of mitochondria in health and its failings in disease. Advances in this area could have far-reaching implications for numerous conditions, including ageing, neurodegenerative diseases, cancer, infectious/immunologic, and mental health.

In many respects, we are just getting started and today we are even further emboldened in our mission as inspired by our Hero, Frederik.
For anyone who is inclined to donate something in our adored Frederik’s memory, please consider donating to help find therapies and a cure for this cruel disease by clicking on this link.

Frederik passed on March 1st 2025, in Paris France, the City of Lights. One light was extinguished, but so many remain.

Over the years on a number of occasions, Frederik voiced his gratitude for having his disease. He cited the intensity of his experiences and his relationships as the reason for this. He felt that there were so many amazing people that he would never have known had it not been for his disease. Speaking to a friend of ours (unbeknown to us until now), he told Andrew, “I am glad that I am the one who was born with this disease. Even though I’ll die from it….and even if my parents do not have the time to save me, I know that they will be able to save other children”. Writing to my wife, our friend reminds us; “you have work to do…and that work is a tribute to Frederik!”

On behalf of Frederik, Julie, Charlotte, Alexander, Mansour and the entire global POLG community, we thank you for helping this worthy cause that will honour our son. We will be resolutely focused on alleviating suffering for the POLG community and other diseases and conditions far beyond, associated with mitochondrial diseases.

We wish to extend our deep gratitude for all the messages of support and love received by our family in this very difficult moment. With our Superhero’s help we hope to turn our deep grief into positive results and therewith follow his unwavering example. His ultimate message is one of hope, compassion, and resilience!
We are all so very proud of you, Frederik. I am so very proud of you! We love you!

Papa,
On behalf of Mama, Charlotte, Alexander, Mansour…..and of course….Mushu