The Basics

Name: Mike Graglia

Title: Founder and Managing Director

Organization: Syngap Research Fund

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Disease focus: SynGAP1 syndrome is a rare genetic neurodevelopmental disorder caused by mutations in the SYNGAP1 gene. The SYNGAP1 gene is located on chromosome 6 and is responsible for producing the SYNGAP1 protein. Mutations that cause a decrease in the amount of SYNGAP1 protein cause Syngap1 syndrome. The protein acts as a regulator in the synapses – where neurons communicate with each other. Without enough SYNGAP1 protein we see an increase in excitability in the synapses making it difficult for neurons to communicate effectively. This leads to many neurological issues seen in SYNGAP1 patients.

Headquarters: Palo Alto, California

How did you become involved in rare disease: My son today is almost 7. When he was 2, we started seeing some delays. We got an epilepsy diagnosis around 3, and that led to genetic testing. At 4, we received a SYNGAP1 diagnosis and like any parent, you reach out to everyone you can and you say, “What does this mean and what does the future look like?” My wife and I have access to a lot of good people, and we came away from that diligence phase with a few takeaways, one of which was that science is moving fast in both genetics and SYNGAP1. We felt it is worth investing our time and our money to make sure things happen as fast as possible to create therapeutics for SYNGAP1 patients. The reason we’re called the Syngap Research Fund is we thought we would just focus on investing in science. We publicly committed to investing at least a million dollars. When we announced we were going to focus on funding scientists and accelerating science, a number of parents were energized by that and asked to help. SRF has kept growing ever since.

Previous career: Worked in finance and strategy in various consulting and philanthropic organizations.

Education: B.S. in Mathematics from Gonzaga University S.J., MBA in finance from Columbia Business School, and M.A. in international economics from Johns Hopkins SAIS.

The Organization
Organization’s mandate: The organization’s mandate is to accelerate the science around SYNGAP1 and get therapies for kids in a timeframe that matters. The specifics have evolved. Two-and-a-half years ago, we were focused on raising money and funding postdocs and labs that already studied SYNGAP1. A year ago, our focus shifted to getting scientists with valuable training (e.g. epigenetics and proteomics) involved in SYNGAP1. And in the past year we have come to prioritize gathering quality patient data.

To meet our mandate, our priority has become clinical trial readiness. I’m aware of multiple labs that are making great progress in SYNGAP1 biology and biochemistry, as well as companies that are becoming fascinated by SYNGAP1 for both scientific and compelling commercial reasons. It makes sense that we should prioritize anything that will benefit more than one of them—making sure there’s data in place for clinical trials, making sure that certain animal models (e.g. humanized mice) that nobody has are built and accessible to everybody. Anticipating roadblocks, regardless of who’s going to hit them, and clearing them in advance. That is how we get a therapeutic intervention to patients as fast as possible.

Organization’s strategy: I see rare disease as a remarkably challenging space. A few jobs ago, I was a strategy consultant for Boston Consulting Group, where I worked for most of the Big Pharma companies and dealt with tricky but defined strategic questions. In rare disease it is even harder because there are so many unknowns, so few resources and the miniscule playbook is constantly under revision. 

You’re constantly creating the big picture of the steps toward therapeutics out of the mosaic of all the individual projects, asking what is it that’s missing today and how do we meet the need? There are so many gaps to fill that strategy must constantly evolve. The strategy today is to make sure that patient data is well-organized in anticipation of clinical trials and identify and proactively address any roadblocks that would stand between the science and a therapy for a child. 

Funding strategy: The mantra of SRF is Collaboration, Transparency, Urgency. Our funding strategy has five parts, the first two embody Collaboration, the next two Transparency, the third embodies Urgency.

  • Use funds to the biggest advantage. Science is expensive. While our funds feel big to us, they represent a small fraction of what research costs. So we look for opportunities to fund a researcher, or a machine, or an add-on to an existing program, so that our dollars are targeted to augment a funded project.

 

  • Trust but verify. We give funds to labs we believe will put the resources to good use, but we insist on pre-agreed milestones, clear reporting, and no overheads. Universities struggle with this but they come around. When institutions with multi billion dollar endowments ask small parent-led charities to pay overheads and give no-strings grants (which seems to be where they all start) it doesn’t take long to point out the absurdity of their position, but those are interesting meetings. I haven’t agreed to those conditions yet, and we never will.
  • No overheads. As founders we cover all costs that are not grants that advance science and data. This way donors don’t have to wonder how much of their money is funding real work and how much is paying for operating expenses. 100 percent of gifts to SRF go to science. 
  • Project first. Once we find projects we share them with the community and ask them to support the work. People are much more likely to support an X project in the Z lab than they are to write a check to SRF for general purposes. We report back to our community about how each is going.

  • Be opportunistic for great opportunities. Time is brain. When great opportunities come along, we can’t always wait, so in a couple of cases we agree to support projects before we have raised all the funds just because they are so compelling. In these cases the Founders are taking the risk. But so far the community has come through every time.

What’s changing at your organization in the next year: My focus for the next year is engaging the patient community at scale. SYNGAP1 is radically under-diagnosed for a variety of reasons. It’s hard to find our kids in the clinic–they are too easy to miss. The seizures start at different times and vary in severity. Honestly, the sleep and the behaviors are also serious challenges, but clinicians don’t always hear it when parents mention these. Through the efforts of SRF, our Roundtable at AES, our outreach, programs like Invitae’s Behind the Seizure and the increasing prevalence of genetic testing, this is changing. Studies show us that if you test 200 people with intellectual disability and epilepsy, one or two of them will have SYNGAP. So our patient community is going to grow dramatically. The question is, “Are we ready?”

What I’m always saying to my board and my team is that if we’re not able to handle 10 times the patients in the next few years, we’re doing it wrong. Our way to support patients right now is to get on the phone and have the same set of conversations with each new family. I’m focused on getting the frequently asked questions written up and documented on our blog. Due to some amazing parents, this is happening. We are also building a digital system (website, CRM, email) so that we can support and engage more families. So scale is one problem. 

Problem two is equity. If you only answer that question in English, you’re exacerbating existing inequalities. What happens when all the Spanish-speaking people in Latin America start getting diagnosed? How are we supporting the people in China–where there are only 30 diagnosed cases we are aware of? Science tells us there should be thousands!

One of the things we’ve invested in during the past few months, and we’ll go live in the next few weeks, is a website that will work in multiple major languages. You can’t be a part of this community and not care deeply about all these kids. We have to make sure we’re at least sharing what we know with all diagnosed families. The focus in the next year is to be able to address an ever-growing patient population and support them with information, but also to communicate that there’s every reason to be hopeful. They need to be optimistic because there is work to do–we need them to participate in our Ciitizen Registry and the trials that are coming soon– but also because the alternatives aren’t good. This disease can eviscerate people. Parents don’t sleep. People lose jobs, some go bankrupt. Marriages fall apart. The mental health challenges are real. 

Management Style
Management philosophy: The idea behind SRF is that it is a community of parents who want to change the future for our children. It’s a place where people can come and act on their vision. My preference is to give people lots of rope and let them go—just as I did in corporate environments–and some parents love that. What I’ve learned managing an all-volunteer organization of parents, is that I had to broaden my approach. Some just want to help, they don’t have a master plan but they see good things happening and they want to help. These folks need clear asks, so that’s what I give them. Net: I want people to be empowered to make a difference because we all have too little time and we’re all running on fumes since our kids are sick. 

Guiding principles for running an effective organization: Focus on why we’re here. The problem of rare disease is that there’s infinite need, nowhere near enough done, and everybody’s got a good idea. When I’ve got a board of 11 other families and everybody’s got a pet project, I say, “Okay, what’s going to help the kids the fastest? What actually matters? Where do we focus our limited time and energy?” I bring people back to that question all the time. We will always support scientists who demonstrate a genuine interest in our kids, who are fascinated by the gene and willing to collaborate to accelerate science, but we need to focus on and prioritize our efforts in gathering patient data. Therapies are being developed. The only way to have clinical trials happen next, without delay, is to have patient data ready.

We are often solicited to fund a traditional Natural History Study but we always questioned the return on investment: it’s expensive, requires a lot from families (travel, more medical tests) and realistically can only be done on a small portion of the population. We always look for efficiency – we are compelled by a profound sense of Urgency. Then Ciitizen came along and what Ciitizen does is gather up medical records, normalize, and standardize them. They take advantage of all the testing that’s already been done to all these kids. And they put it in a format that hopefully will make it useful. And by the way, it costs a fraction of a natural history study and is an order of magnitude faster. When I was introduced to Ciitizen, I said that this is the best thing I’ve ever heard. The price is affordable. If I have to pay for all of it, that’s fine. As a result of that, we now have the largest instance of a rare disease population on Ciitizen’s platform because we were able to move fast. 

So our priorities, starting where we are today: we need to get every parent to sign up for this and to share their data and to understand that this will help all of our kids. And then the next thing on the list is spreading hope and letting people understand the speed of change. And the next thing is raising money and funding research. Two and a half years ago, I didn’t get it. We jumped right to funding research in labs that already study Syngap. This is a tough space in which to be effective because there’s no guidebook. Keep people focused on what matters most and how we can have the most relative impact, even while the landscape changes, I think is the answer to your question.

Best way to keep your organization relevant: To be relevant, we need to make sure we’re filling the gaps in research and in clinical trial readiness. But we also need to recognize that for us, the title of patient advocate should be people who are pounding the table and insisting that the urgency felt by families is felt by everybody else in the ecosystem. There are some patient advocates out there who focus on education around their disease, but they don’t have an agenda. We have the path to treatments always at the top of our mind, so I feel like part of our job is to be a little bit of a pain in the ass. When researchers rattle off what they’re doing I’ll ask, “How does that translate?” And then they have a practiced speech on basic science and how it’s important and good things will happen if we just keep funding basic science. I’ll say, “Yes, but my kid is sick. What about what you’re doing is going to help my kid get better faster?” If you can’t answer that, we don’t have much to discuss because a lot of people can answer that, and I need to focus my support on them. 

Why people like working with you: Because I am only interested in the results. People who share my passion for helping our kids like working with SRF because we drive to results. With me, there’s not much veneer. It’s clear what I want and it’s clear why I’m here. People who can handle that intensity enjoy the clarity of working with me. People who enjoy their comfort zone or their own promotion, less so.

Mentor: I don’t call people up enough to ask for advice, so I’m low on mentors, but I have lots of heroes in the rare space. Mary Anne Meskis is amazing. I basically built SRF as a copy/paste of Dravet Syndrome Foundation. Kim Nye at the TESS Research Foundation. Nasha Fitter and Nicole Johnson at FOXG1. Bo at USP7. Nicole Boice at Rare-X. Daniel DeFabio with Disorder: The Rare Disease Film Festival. Then there is my board and other Syngap leaders. A real gift in this job is that I get to talk to other SYNGAP1 parents every day and learn about their lives. Everyone is running a family, keeping a day job, supporting a sick child and their siblings AND volunteering for SRF. They are all amazing. Example: Hans Schlecht has been out there slogging away. He’s an M.D. He’s a dad. He’s read every paper on SYNGAP1. He cares deeply about his kid. He’s the smartest guy I know. Vicki Arteaga is another director who came to me and said, “No one’s doing anything for all the families in Latin America.” I said, “Great. You’re the head of SRF, Latin America.” And in February 2021 we’re going to have the first Latin American roundtable in–entirely in Spanish– with six speakers talking about their research as it relates to SYNGAP1. All Vicky. There is no shortage of inspiration in the rare disease space.

On the Job
What inspires you: I’m inspired by the people I meet with great passion for their space in the race to cure rare diseases, whether it is a scientist working in an academic or industry lab, or a parent connecting with other families, or a clinician who is determined to understand and help our kids. What’s exciting (and what’s frustrating) about the rare disease space is that there is so much work to do. There is so much opportunity to have an impact. Science is progressing fast. I don’t know if we’re going to cure our kids in a few years, but we sure as hell are going to be able to help them. I love being able to say that to people and I can’t say something that I don’t believe. I would say my wife, my affected son, and my typical son inspire me, but they are more my inspiration, my urgency, my peace.

What makes you hopeful: What makes me hopeful is that there are technologies out there that can help our kids. I know there are ways to get those technologies into their brains. The Ciitizen data we have collected is going to further accelerate things–we have to keep working at getting patients signed up and consenting to share their data. 

We just have to put these puzzle pieces together and we’re going to be able to help the kids we love today. And we’re going to be able to help thousands of patients who haven’t even been diagnosed yet. It’s exciting to know that work we’re doing is going to help these kids because they have suffered too much. 

Best organization decision: A year-and-a-half-ago, we expanded the board to represent a dozen families. And that’s led to a lot of hours of meetings, but it’s also led to greater ownership by the patient community and greater patient voice and how we do things. There’s no turning back from that. Ensuring that we are 100 percent parent and volunteer led is the right decision.

Hardest lesson learned: The hardest lesson learned is that you can’t make every single part of the patient community understand our mission and our projects right away. The challenge I’m facing right now is bringing more people along on all that is happening while keeping current projects moving as fast as possible. It’s that balancing act. Families come along with the intense urgency we all feel and less information than they need. We work hard to translate our projects and vision to the entire community, but not everyone appreciates the radical complexity of this space, and not everyone agrees with our priorities and strategies. But everyone doesn’t have to. We have a strong group that I’m proud of. And whether you are part of our organization or not, we are all Syngap parents first. 

Toughest organization decision: The hardest personal decision was deciding to leave my job and run this full time. For this organization to grow, we needed somebody to work on this around the clock.

Biggest missed opportunity: The missed opportunity was not working on getting in sales mode on SYNGAP1 with every scientist who could do something useful earlier. In the beginning we concentrated our grants to the established scientists in our space. While it was a natural way to start, I’m not sure that it was smart. It took us a year or so to realize smaller grants to more scientists was a better strategy. Having said that, we have seen a strong increase in the number of scientists of different specialties adding SYNGAP1 to their list of genes studied.

Like best about the job: it’s very hard to find a job where your heart and your mind are all challenged and engaged, and this job is all of that. What I love about this job is–aside from the fact I’m doing something that I know is helping my son and the hundreds of diagnosed patients like him– is that it demands everything. It demands the heart, the mind, and full attention. And you never, ever get bored.

Like
least about the job: It’s never done. No matter how hard I work and how tired I am at the end of day, there’s still a thousand things on my list. 

Pet peeve: People who think that this is about them. It is not. It is about helping our patients and ensuring that those who cannot speak for themselves have advocates. We are Rare Disease Patient Advocates. We aren’t drug developers. We aren’t policy makers. We aren’t scientists. We may have to wade into these areas but our job is to insist that researchers, scientists, policy makers and the public keep our patients in mind. Some people get caught up in the importance of it all, they start talking about NDAs, secrets, things they don’t have time to explain. It’s ridiculous. We are all in this together, rare advocates helping our loved ones and each other. When people show up more interested in power, politics, and self-aggrandizement than the mission, then I move on. There is no room in SRF for any of that madness, our kids are sick, and Time is Brain.

First choice for a new career: In a dream world where I did not have to worry about my kid having a therapy? Something that helps me support people who are the next wave of rare disease—help other groups figure out their critical path and think through what to focus on. Basically, I want to be Terry Jo Bichell from COMBINEDBrain, I need to add her to the heroes list.

Personal Taste
Most influential book: Markings by Dag Hammarskjold, I’ll give anyone a money back guarantee on that book, go get a copy.

Favorite movie: Peanut Butter Falcon

Favorite music
: Rush

Favorite food: Sushi

Guilty pleasure: Barolo. I’m Italian that is the best red wine, ever.

Favorite way to spend free time: Yoga



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