Listening to Loss
I've dealt with two losses about a month apart. It makes it hard not to think there's something divine about our experiences—that life isn't just a mathematical collection of deterministic and random events. Academia has deeply ingrained in me the scientific method, teaching me to develop tools in search of well-supported theories about how the world works, always within comfortable confidence intervals. Yet the more deeply we explore our world and universe, the more we realize our tools are merely blunt instruments, feebly attempting to capture the wealth of invisible cosmic forces.
How can we possibly find words to describe such profound and deeply personal events in our lives? In our quest for understanding and healing, we often turn first to the rational mind, attempting to process our wounds, grief, and loss through careful reasoning and analysis. We find ourselves desperately trying to make sense of what has happened, focusing intensely on the practical details and logistics, perhaps even entertaining futile thoughts about reversing senescence. Yet we discover, sometimes painfully, that even the most rigorous logical analysis cannot bring peace to an inquisitive mind that must, by necessity, eventually yield its carefully controlled mental territory to the raw power of emotions and feelings. This fundamental transition from thinking to feeling seems particularly daunting when the very gift of intellectualization—a trusted companion that has helped us navigate countless challenges in the past—must now be gently asked to step aside, to take a deep, nurturing breath, and to create a sacred space of quiet where we can truly listen.
There are many levels to listening, each requiring a different quality of attention and stillness. Only when we truly calm our racing thoughts and quiet the constant chatter of our analytical minds can we begin to perceive those subtle, invisible forces that flow through our body, mind, and surroundings. Deep within us lie innate tools, gifts we've carried since birth, waiting to be activated—tools that allow us to tap into vibrations and signals that initially seem imperceptible to our ordinary senses. Like a dormant windmill suddenly catching a gust of wind, this awareness can unfold dramatically, revealing an overwhelming wealth of information and subtle cues that were always present but previously unnoticed. The truest, most profound form of healing emerges when we dare to connect authentically with our raw emotions—our deep-seated pain, our burning anger, our gnawing frustration, and our hidden shame. This healing journey demands we develop special listening skills, ones that enable us to sit patiently and courageously with these intense feelings, creating a safe space where we can process them fully and completely, truly hearing and honoring the important stories they have to tell.
As we develop and strengthen these deep listening tools, we begin to see the forces around us and realize we aren't alone. Saying goodbye isn't really goodbye, because these forces live within us. The ones we've lost have shown us how to love, how to play, and how to experience life every day. We just have to learn to listen.
The Power of a conversation is connection
This past year has been one of the most difficult moments in my life. My brother was diagnosed with Grade 4 glioblastoma and had four surgeries to remove the tumor, stop the bleeding, and put an implant to prevent pressure from building in his brain. My family and I had to set up his care, manage the logistics of care, and cover the costs. I spent six hours a day waiting to answer a generic phone number from the hospital. I wouldn’t want to miss the critical dense medical information that I had to distill for my family to decide on my brother’s care. Once missed, then who knows when I will get the callback or know who to call.
During those 6 months, I was speechless. I didn’t know how to convey the confusion, anger, and frustration I had with dealing with inconsistent information and such an inefficient medical system. I didn’t know how to ask for help because I was in the thick of figuring out the problem, collecting data, and sorting the critical tasks at-hand. I was at a loss for words. After those 6 months, my brother was stable and all the care logistics could be done without new information. I started to sit back and processed the “what just happened” moments. I reflected on the times I had to leave my kids when I flew down to see my brother or the moments I lashed out because I felt overwhelmed with the screaming. But in fact, my emotional bucket was empty and I didn’t have enough to tolerate even loud noises. I felt nonfunctional because in my mind I was still unfairly comparing myself to my 20-year-old self and wondered “how come I can’t think as fast or still retain the same memory like before”.
My deepest healing started from a conversation with a friend. Even though I didn’t necessarily have the words to describe the mountain of feelings, she just sat and started drawing with me. We didn’t do anything specific except a marker on thick paper. Slowly our parallel play opened us up to talk without eye contact. Something about making eye contact when you’re vulnerable cuts so much deeper and the avoidance of the eyes helped me open myself up to listen. I heard her story of losing someone dear to cancer as well and that opened my heart to listen deeper; deeper to the loss and grief and deeper to the tragedy. Part of coping and healing is processing the tragedy and slowly evolving the feeling of grief as unexpressed love.
For me, the deep sorrow is deeply rooted in the assumption that I had more time with my brother and that we had time to share a rave one day, and now that day will never happen.
After 6 months, I searched for space to delve into my connections with myself, my feelings, my body, and my relationships. I teased apart the important connections I needed to make with myself and understand how my body, mind, and feelings worked as a 40 year old woman. I began to listen to my inner voice and hear them to understand where they were coming from. I dove into my ancestral past and delve deeper into the generational trauma of my parents’ escape from the Vietnam War. After my excavation, I have learned to redefine what it meant to love myself. I envisioned myself as art and admired myself for the first time after believing that self-love is defined by the people who love you. I realized that I love and should love myself more than anyone else hence I should be more patient, more gentle, and more kind to myself. Even the ones that love us the most can never love us the way we love ourselves. That is what I promised to do and honor my brother’s tragedy: I will love myself more and honor my feelings. Slowly but surely, I am building my foundations and principles on how to connect with myself. This connection makes the healing journey more powerful and I hope to teach these skills to my children and folks suffering from the same pain.
Glioblastoma patient advocate
In August 2023, my younger brother was admitted to the emergency room and diagnosed with an aggressive grade 4 brain cancer, called Glioblastoma.
Learning that he had 14-16 months, I suddenly became a caregiver and supported my mom who is a non-native English speaker and living with low income.
During my journey as his caregiver, there was overwhelming medical and financial information that our family had to process, adjust, and adapt to successfully help my brother in his care. This includes doing my time-consuming research to ask the doctors the right questions about the treatment options, being fastidious in potential medical treatments, asking for referrals for outpatient services, and following through with authorizations and referrals.
Aside from navigating the medical system, we had to prepare ourselves for the new "normal" when my brother was discharged. We transitioned into the home to include his medical equipment around the house, looking to state and county programs for financial support, transportation services for his daily treatment, and supportive services related to his daily care and hygiene.
I’ve learned that I am not alone. A New York Times article estimated 53 million Americans are becoming caregivers spending +20hrs per week taking care of someone who has suddenly become ill. They are the “backbone of long-term” care for patients who have to lose their jobs and take care of someone without financial support.
I have joined my sister's mission and non-profit, Patient Led Foundation, as a Patient Advocate for Glioblastoma, to provide resources and support for those who are in this journey with us.
Her mission is inspired by being a patient, scientist, and entrepreneur who had to navigate the medical system for her diagnosed retinitis pigmentosa in 2010 with no standard of care. Her challenges taught her the power of shared information and knowledge and self-advocating. Patient Led Foundation is building a community of information and resources to support patients and their caregivers in navigating their care.
- Le Nguyen, Patient Advocate for Glioblastoma
Lead us from darkness to light: Navigating the hospital
In the midst of developing my organoids and helping patients navigate their own cure, I had unexpectedly become a cure guide for my brother’s brain cancer. This was devastating for me and most importantly my mother as I can barely fathom the turmoil she’s going through as a mother of four, low-income, and a non-native english speaker. As someone who is both a patient with a rare disease and a cure guide for others, I started reflecting on the common challenges patient’s with rare disease face and made a to-do list for those who are figuring out how to navigate this as well.The challenges we face
Lack of diagnosis/prognosis. There are a few layers of unknown that patient and their caregivers have to navigate. There is still so much we don’t know in medicine and science. As a scientist we may have a therapy that shows some promise but there are gaps in whether it works in patients. Families believe medical professionals know the answer on how to fix or manage the patients condition, let alone sometimes they expect doctors to know the diagnosis. However, the truth is these answers are still educated guesses and very few tests exist out there that can give definitive answers.Lack of time. These unknown still falls onto caregivers who carry that burden of not knowing, waiting for answers, waiting to talk to medical professionals all the while society forces us all to continue to work and pay the bills with barely 2 weeks alloted grievances/bereavement leave. Even if we don’t have the answers, it’s the timeframe of the unsuspected, abrupt notice of medical procedures, updates, and transfers that interferes with the day-to-day and not to mention the emotional turmoil of fighting and begging work to allow us to take that time to adjust.Lack of medical jargon. This is the another language barrier that caregivers face as most of us barely have biology background let alone the medical understanding of what's happening to the patient. But they are tasked with the responsibilty of navigating and understanding the gravity of these decisions they both have to make.Lack of financial support. Things until a patient and their caregivers having to navigate this. Having to navigate the medical system to get answers, the financial burden, and family dynamics while not having the knowledge or vernacular to speak to it let alone the emotional trauma you’re dealing within yourself. I had to chase down social workers to find local financial support and resources to help pay for something as simple as parking for my mother who came in everyday.Lack of emotional support. These seems like the last thing to provide but it should be one of the first and a calm demmeanor can go a long way in the medical profession. This can also be provided through social workers who are trained to provide local resources to mental health professionals as well. Persistent stress is emminent in medical cases that take a long time. The marathon of chasing doctors, nurses, social workers, and case managers takes a lot of time and a toll on your mental health. Burnout becomes common and the guilt of not being able to provide emotional support for the patient is eating away your hopes and strength.Teetering between grief and hope. There are days when you look at your child or family members suffer and grief seems to swallow you into this dark, infinite space of sadness and emptiness. You lose sense of time and relevance of the world around you and you can barely “function” as a adult let alone a normal human being. In those times of grief, sometimes doing the motion of making breakfast or walking around seems like an empty meaningless thing your body does without intention. Those are the days when you need to establish a process to help ground your mind to your body. I find swimming is my grounding where I can do something aimlessly but it helps my mind remember that I still need to keep this body alive and healthy and are limited by the air you breath. That grounding will help me snap back into my body and engage with my bodily needs again. Grieving the grief helps make space for joy, happiness, and hope. It’s part of the everyday process and if it gets trapped and not expressed, grief becomes depression and potentially prolonging your ability to support yourself and others who need you.
What to do in the hospital
Nurses are amazing human beings. They take care of the patient and most of them are in the dark of the next steps. So please be kind to them. Offer them meals as they are taking 12 hour shifts to ensure the best care while you're not around.Doctors are the gate keepers to diagnosis and prognosis. They are the ones who interpret the data and help provide options for the patient. It's important to know which type of doctor to talk to since each doctor can only chime in on their speciality. Have the nurse help you get the attention of your specific medical doctor to talk about the diagnosis, prognosis, and treatment options.Case managers help you figure out insurances and get the needs/care the patient needs. Make sure you have an assigned case manager. They are typically nurses who know about the medical condition and can help navigate your insurance and what services are covered and local clinics and facilities that will help the patient.Social workers will connect you to financial resources that the hospital or clinic provides. They should connect you to local disability resources provided the local, state, or federal government. Ask for long-term parking permits and vouchers to subsidize your hospital stay. You might consider searching for financial support for the patient and potentially enroll them into unemployment and/or disability insurance.Don’t forget to find mental health providers that can assist you as the caregiver. In the end, you are a project manager for the patient and helping the navigate this while they can’t is helpful.Occupational, speech, and physical therapist are good people to meet. This means the person you’re caring for are on the mends. Occupational therapy and speech therapist help the patient learn how to do functional things like stand up and learn how to walk while speech can help with things from speech to swallowing.Who is the beneficiary? The beneficiary takes care of and/or manages the patient’s assets. Make sure to follow-up with bank accounts and credit cards.
My brother is going through his 2nd resection today, so I hope I can provide an update on the to-do list on how to navigate medical care outside of the hospital. For now, we continue to provide space to grieve and clearance for hope.
Love Light
From One to Many
Another poetry submission that describes my rare disease and what inspires me. I hope this inspires all of you who are conquering the day-to-day and fighting a good fight.
Poetry submission: A stranger’s perspective on my vision loss experience
I’ve submitted a poetry submission and I’m hoping it will get published to provide a patient’s perspective on losing their vision. I had 30 minutes to write and this is what I felt deep down inside during a time when I was learning how to grow stem cells and it’s been a little over a decade since I’ve cultured cells. I was getting critiqued without compassion and felt defensive because yes I will defend myself. I’ve also had a few people yelling at me about whether I was just “using that cane as a prop” because I was able to see when it was fully lit versus when it was dimly lit.
What helps me the most during those times is to understand that people are projecting their frustrations onto me. So it’s not me who’s the problem, but it’s their inability to love and find compassion within themselves. Because so many of us have gone unloved for so long that we have forgotten to do it.
Phase 1: my stem cells
For the past 6 months, I’ve been training myself to make stem cells. Of course, what does making stem cells entail? Some may have learned early on that your body stops producing stem cells except in your hippocampus and olfactory bulbs. My friends and family would ask why are you doing this? Or more importantly, when will you stop going to school? Well, I hope this post will answer all of your inquiries.
First I want to provide some background into stem cells and give attribution to the amazing feat that deduced a complex process of literally Benjamin Button-ing adult cells back to their nascent stem cell state. Around the mid-2000s, scientists figured out a way to take adult cells such as fibroblasts and later peripheral blood mononuclear cells (PBMC) and reprogrammed them into induced pluripotent stem cells (IPSC). After many passes through different combinations of transcription factors and oncogene, they deduced the necessary genes to reprogram human cells down to these main activators: KOS (polycistronic Klf4-Oct3/4-Sox2), Myc, Klf4 (because one is not enough) (see this amazing review of the history of stem cell historical discoveries Omole and Fakoya, 2018).
From what I hear, it’s one of the hardest cell culture protocols. So why am I going down this path of creating my own stem cells? Well because my masochistic tendencies love to explore the hardest but shortest path of modeling my own disease.
“Why couldn’t you just hire someone to do this for you?”
Well, science and labs are in short supply and even if I paid someone to make my stem cells — which you can — I am still short of modeling my rare inherited retinal disease. Stem cells are only a precursor or the first step to making a disease model after a patient’s specific gene mutation. The next step is to take stem cells and study the cells that best represent the disease. In my case, a retinal cell is the best way to study my retinal disease.
“Why do you need to study retinal cells from humans? Couldn’t you study this in animals?”
I wish I had the luxury to model my disease on animals. Here’s the catch, EYS does not exist in rodents. I repeat EYS gene is nowhere to be found in the rodent gene and this includes mice, rats, squirrels, and tree shrews (we’ve looked). But we have studied them in our favorite fish and invertebrate animal model, zebrafish and drosophila. Although we can study it, the EYS gene between humans and zebrafish shares about 33% similarity. This makes it hard to map the mutations that cause my disease from humans to fish and vice versa. Second, if I were to find a treatment using gene therapy and I had used a fish to model my disease, then I would have to design the therapy for the fish first and then I would have to go back and re-engineer that therapy to my gene. So given my conundrum, I needed to find a lab in the Bay Area that would study retinal diseases using patient-derived cells. In fact, I found professor Deepak Lamba (lab link) who models retinal diseases by making mini-retina clusters in a petri dish called retinal organoids. He works in reconstructing the retina morphologies from patient-derived stem cells so we have a better understanding of the mechanism behind the disease. If you wanted to know how I ended up in Deepak’s lab, check out this post here.
So I started my first cell culture in a little over a decade by grabbing a frozen aliquot of PBMCs (peripheral blood mononuclear cells) that have been collected from my blood draw back in June (boy, do I look like a freshman grad student, innocent and naive).
Back in June, I pose with my my blood draw and getting ready to get it processed in the lab.
I’ve attempted 2 times to reprogram the PBMC to IPSC and I’ve always stopped short 35 days after reprogramming to find either no colonies or small colonies that went nowhere (see the image). I’m telling you it’s very sad. They just refused to grow. What gives?
Day 34 and colonies were no more 16 cells.
Third time’s a charm, right? Well, the charm came from reprogramming fresh blood right after finishing up running some tests for ProEYS Natural History Clinical Trial that I am in (see link to learn more). And yes, it made a HUGE difference. Because in less than 13 days, I got colonies so big that I started picking them early. So far every 4-6 days, I kept picking colonies and started my passages. Today I am on passage 3 of taking undifferentiated IPSC colonies and culturing them so that we only have undifferentiated IPSC colonies. This guarantees that you have cells that are most likely stem cells and not cells that have been differentiated into something.
Stem cells packed into a single colony compared to very spaced out differentiated (non-stem cells). Top left: 10x magnification of colonies. Bottom left: 4x magnification to see entire colony. Bottom right: 20x magnification to see packed cells. Top right: non-stem cells not packed densely into a colony.
Now that I am finishing up the first phase, the second phase of making mini-retinas (retinal organoids) will start as soon as the first of February. This second phase is long and arduous and requires the forethought of making enough organoids that can survive more than 150 days, which is when photoreceptors start to appear. It is then that we hypothesize that EYS protein will express near the base of the outer segment as seen below in macaque retinas.
EYS shown in green is expressed at the base of the outer segment of both rod and cone photoreceptors. You can see the higher expression of EYS in the outer segment of blue cone receptors, which is co-stained with blue opsin (Yu et al., 2016).
Then we beg to ask, what does EYS do that is so important in the retina? What do the mutations do to my retina that renders me to lose my vision in my 30s but somewhat perfectly intact until my adult life? Will I even see any differences in the mini-retinas between my mutations vs. healthy ones? I hope to answer some of these questions in Phase 2.
If I could get any help in this journey, it is to connect to experts and collaborators who are interested in the following unknowns:
The preclinical requirements of getting treatments prepared for clinical trials. How does an N-of-1 (1-to-N) toxicology screen look like for someone who is screening treatments on retinal organoids? Is organoid or cell survival enough?
Are there any therapies worth testing that can preserve and protect existing photoreceptors? It could be anything from NAC (n-acetyl-cysteine) to Antabuse and metformin.
What are some worthy experiments/questions besides protein/transcript expression in these organoids? Harder questions like how to search for other protein-protein binding interactions? How to target for each of the four different isoforms?
Until then, spread the word, the awareness of (1) rare diseases and how most of them are left unstudied, (2) those who are fortunate like me can find funding to research my own rare disease, and (3) there are pathways being paved now as I continue to help patients through Perlara. Never give up hope.
Chapter 1. Diagnosis
How can we improve the patient experience and journey? Well before I answer that question, I wanted to share my experience and maybe some of this resonates with you. This is the breakdown of how this all started:
Geminid Meteor Shower in 1998
I was out with my friends in high school to view the meteor shower of the year. As a nerd, I had gotten special permission to lounge out on the rooftop of music class to view the meteor shower. We set ourselves up with EANABS and our favorite snacks and abruptly my friends turned, gasped, and marveled at the reverse, firework spectacle above us. It was gorgeous so they say as I doubted whether my friends were teasing me. I felt the explosion of confusion and pain flood inside me as the surrounding wonderment slowly drowned out. It was clear what was happening because I honestly did not know what did happen. But I walked home that night silent and alone among my good friends.
Since then, I nagged my optometrist every year about that night without the vernacular or comprehension of what happened. I did my best to explain my observations, “I just couldn’t see the stars.” And for 10 years, I was told that I had to adjust to the darkness a little longer. The advice made sense except after a long hour of sitting in the dark, my eyes never adjusted and my center of gravity felt disoriented instead. Or maybe it was my lenses was not corrected enough, so we again changed my prescription, and still 20/20 vision. In an era of AOL, I relied heavily on my optometrist (remember AIM?). So searching for “special eye doctors” and content was accessible as encyclopedia books. You heard me right, there was a time before Wikipedia because the internet was barely learning how to walk. While navigating the infant stages of Facebook and MySpace in college, I became the reverse vampire exploring campus life between the hours of operation 9-5 pm, and having an exclusive social life no later than dusk.
Even then I had tried to party which ended up being a flower wall because of exquisite dim lighting that was every bar and every party scene go to the mood setter. It was a buzzkill as I realize my preferred or vision-friendly settings are cafes and boba places.
These “life adjustments” were just a short preamble to the modifications I endured when I begin my journey into grad school.
Diagnosis
Orientation week at Stanford was a rush and full of excitement. I had just spent two weeks prior partying with my friends and family at the NIH and SoCal, so I was ready to be a serious graduate student and learn the ways of academia. After getting myself acquainted with the social structure at Rains, I had one more thing to check off my list which was setting myself up at the Vaden Health Center. It was painted with Stanford's iconic cardinal colors and it felt more like a tech office than a health center with the front desk dressed with educational pamphlets on self-care. I remember my first visit to my optometrist there and after so many years of saying the same thing, I figured I just note that I can’t see stars. I remember his uncanny response, “Oh, we need to refer you to an ophthalmologist.” I have never heard of ophthalmologists and I was both excited and scared. I was for the first time being referred to a doctor that knows something about me not seeing stars. I felt taken care of.
After several hours of retinal scans and visual field testing, this was the rub: I had retinitis pigmentosa and there was nothing I can do about it. In that hot moment, the adrenaline of joyful validation completely electrifies my muscles while instantly a dark shadow of depression sunk that validation into the deep abyss. There is not much that has been known about it. I asked do we know what genes are involved and can I get sequenced? My ophthalmologist replied, I think there are some guys in Oregon who are doing that but nothing available to patients right now. There are places like the Lighthouse that can set you up for a vision cane. You don’t need it now but the next step is for you to measure your progress on an annual basis. There is this one study that demonstrated that 10,000 IU of Vitamin A slows down the progression but it’s not statistically significant.
A bombardment of questions pierced through my interrogation: do I need a vision cane? I just drove over here and I have a car, should I stop thinking about driving? So 10,0000 IU of Vitamin A to slow down the progression of my disease? I will take what I can get. Anything to buy me some time to think about this. Am I going to be blind tomorrow?
Leaving the clinic more confused than validated, I began to reconsider my clear career path of becoming a professor. Would becoming a professor help me further the work that needed to be done. I couldn’t even get the care I needed and let alone find the support and communities. I did consider it. I went to all the talks and my first one was from Dr. Daniel Palankar he developed Argus, a cyborg CCD camera implant onto the optical nerve that replaces your complete loss of vision. There was also Dr. Stephen Hicks who was one of the first to implement google glasses technology and augmented and enhanced. It was the closest thing to helping those who are still suffering from loss of vision and still have some vision left and amplify their existing vision with the help of some augmented glasses.
Before I knew it, I had already shifted course. I began switching my life pursuit from a career mentality to developing a cure mentality. How do I begin to help myself and those who suffer from the same infliction? Where do I begin? Or do I just accept my fate and learn to adapt? How I answered these questions defines the life ahead and most importantly transforms it into the mission I’m working on today.
NIH grant approved to develop my retinal organoids
Monday, April 26th, 2022, I received a 10 pm email from Deepak Lamba (link to lab), a professor at the University of California, San Francisco (UCSF) whom I’ve been corresponding about his work on stem cell technology and development of retinal organoids. The email says, “I just saw a notice dated tomorrow (4/27) that your supplement got approved. Congratulations and welcome to the lab!”. My eyes widen and immediately I jumped out of my chair before it hit the bookshelf, I got to Matt and said, “I got the grant!”. A few moments later, my doctor, Jacque Duncan — who is still running the Natural History Clinical Trial, introduced me to FFB, and the low vision community — has emailed me to congratulate the approval of the grant. It was a moment of disbelief, joy, and warmth from the community of people who have supported my journey thus far and further.
What is this grant and what does this mean for me?
I had just received approval for a Re-Entry Grant funded by the National Institute of Health (NIH), which funds individuals to return to academia after leaving between 6 months and 8 years (link). For those interested, you need a PI to sponsor you and submit the grant application which is comprised of (1) biosketch, (2) grant proposal, and (3) personal statement. Your PI needs to submit a budget detailing the next 2 years of the work and more supplementary information. Although many saw this as a way to develop their skillsets, for me, it meant I can research my specific variant and understand how EYS is causing retinitis pigmentosa. It meant that if we can develop these retinal organoids, which are mini-retinas grown in Petri dishes, we can model one of the first late-onset retinal diseases and observe morphological differences. Furthermore, we can develop and experiment with several therapeutic approaches, such as gene editing directly on my retinal organoids.
What is my ultimate goal?
My biggest hope is that I can transfer this knowledge, this self-cure guide experience to others suffering from rare diseases. It can be this particular path or similar paths that lead to the endpoints needed to derisk the therapy and demonstrate efficacy early in the preclinical process. If we can make these observations early, we increase the chances of success later and make collecting data less expensive for families and foundations. These points alone are priceless for the families and communities inflicted by rare diseases and who rarely get an opportunity to find a researcher working on their disease. Can we improve modeling pathology systems and get more insight into therapeutic efficiency, drug delivery success rate, and toxicology? Each of these insights would easily cost $1M and if we plan to find a treatment plan for every 7000 rare diseases, then the infrastructure and the cost need to change dramatically. Here’s one vision of creating a network of mini-CROs to help build this affordable infrastructure (link) and another is to create a research institution like Broad that dedicates a lot of resources to studying rare diseases (link). As we build these infrastructures for the N-of-1 or N-of-few, we see the entire clinical pathway benefits and we see a more robust system that can take on more diseases that don’t fit the typical medical cookie-cutter mold. We are able to accommodate the rest of the medical cases that are one to two standard deviations and EVEN outliers.
We cure via decentralized micro-labs
Gene Fixer’s clubhouse conversation focused on building a decentralized micro-lab ecosystem that enables research for rare diseases to collect preliminary data and derisk the opportunity cost of unknown diseases. This is the only way we can scale research for over 7000 rare diseases just in the U.S. (NIH NORD, 2019). Here’s how dire the situation is:
29,000 diagnostic and medical labs in 2022 (IBSworld, 2021)
The NIH funded grants breakdown based on the type of disease in 2020 (NIH, 2020)
$17.6B went into clinical research (preclinical and clinical trials)
$10B went into genetics research
$10B went into neuroscience research
$8B went into infectious diseases
$7.0B went into cancer
$5.9B went into rare diseases (< 0.002% of NIH funding)
And the funding mechanism is dire because it is hard to get funding for a rare disease when it does not affect many people and therefore the impact feels small. Most grants will fund $5-$20M for 5 years and in the best-case scenario, we might have 10 labs working on one rare disease.
We need a better plan, a better infrastructure, a better funding mechanism, a better business model to build more resources to do the research for the 30 million individuals affected by a rare disease. Some of the ideas around creating micro-labs or micro-CROs also included digital infrastructure to manage the data and data sharing.
Hackathons are a great way to get a lot of people to solve a problem. How about we take university classrooms and convert a biology course studying protein trafficking and train them to solve protein trafficking diseases? What if these classrooms became dozens of hackathons throughout the U.S.? And what a better way to learn about biology is by solving the problems of biology. These universities don’t have to be the Harvards and Stanfords, but liberal arts colleges that have the infrastructure to do cell culture, imaging, microbiology. We can enable so many more people to the conversation and truly decentralize the efforts funded by the NIH.
To hear a clip of the Gene Fixers on this, click here. If you would like to collaborate please reach out via [email protected] or through Contact Us.
natural history clinical trial for eys
I wanted to share my personal experience of losing my vision slowly through the lens of a patient scientist. I got the opportunity to be part of a four-year Natural History Study for my gene-specific retinal disease called ProEYS. This data collection effort funded by the Foundation Fighting Blindness (FFB) is to better understand the disease progression for patients with variants in the EYS gene. Before this, I was fortunate to learn about a free genetic test panel that was conducted by Blueprint Genetics in collaboration with FFB and once I got the gene and the mutations in that gene, I was lucky to meet a genetic counselor to help enroll me into the study, which started in 2021. Lucky for me I qualified for the study but before then I had no idea. When I was diagnosed in 2010, gene sequencing wasn’t as readily available to patients and consumers as it is now.
So what does a study like this mean? Do I have a treatment already? No. It is the first step in the right direction. Although retinitis pigmentosa (RP) has the same underlying mechanism, which is the degradation of rod photoreceptors, not all genes related to RP have the same degradation. Because there are at least 80 genes related to this, there are at least 80 different ways and not including individuals who may have crossover in these expressions. Some are more severe than others and some may live with some functional vision well into their 80s. A lot is still unknown. So these studies are helpful.
So far, my visits have been once a year, which entails at least 4 hours of OCT, VF, and additional measurements that are related to the study itself. If they have data that is specific to the research, they might be exploring new ways to measure the disease, in which case, you’re not privy to that data. So keep that in mind when participating in these natural history studies. So on top of these visits, I still visit my doctor at the Casey Eye Institute in OHSU because I get all the raw data from my measurements. I HIGHLY recommend it.
So next steps, I’m being patient and waiting to continue to collect the data, but I hope my next efforts / journey related to potentially working on creating my own retinal organoids update will bare more results. Until then, self-advocate my rare disease crusaders!
This is a visual field captured using Octopus and it’s measuring visual sensitivity of a patient’s visual field. Green indicates positive response to stimuli and dark reddish color indicates negative response to stimuli.
patient perspective for Rare disease day panel
I’ll be sharing my personal journey with retinitis pigmentosa on Rare Disease Day on Thurs 2/24 9am EST. Please register below and listen in on the latest treatments, patient advocacy, and lifestyle resources.
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Retrospection: it was fun to be on the panel and nerve recking. I was the only one providing a patient perspective on a very research-driven panel. I had the opportunity to share my perspective and why building cures in a customer/patient-centric manner can only help your innovation. As someone who has built B2C products, often companies forget the patients and think they can cure the disease. But the success also lies in patient compliance and acceptance of the treatment as well the cost. In sharing the patient perspective, I hope to share not just patient insights but help engineer and design therapies that work from the business model side.
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Innovation in Rare Disease: Making Progress with Cell & Gene Therapies
https://www.syneoshealth.com/events/rare-disease-day-2021
blind american podcast by alex sparks
It all begins with an idea.
I had a great opportunity to talk to Alex Sparks on his podcast “Blind American” where he interviews people who live with retinitis pigmentosa and give them a platform to share their experience and inspirational stories. I met Alex on a Retinitis Pigmentosa Facebook support group and immediately we found alignment on our mission to help more people inflicted with this disease. I shared my personal experience with RP and how my encounters with the medical system brought me to become a scientist, patient advocate, and entrepreneur for the community. Please check it out at the apple podcast