Rare Leader: Danny Miller, Founder and CEO, MEPAN Foundation

The Basics
Name: Danny Miller

Title: Founder and CEO

Organization: MEPAN Foundation

Social Media Links:

Disease focus:  The mitochondria are traditionally thought of as the powerhouses of the cell— generating the energy our bodies need by producing ATP via a series of biochemical processes collectively known as oxidative phosphorylation, or “OXPHOS.” Our mitochondria also make their own fatty acids, and the process is “highly conserved” in evolutionary terms, meaning that it’s found across a range of different species, including yeast, worms, flies, and mammals. Because mitochondrial fatty acid synthesis (mtFAS) is a conserved process going back millions of years, it means that it plays an important role in the ways these organisms function. mtFAS is now being recognized as an important influence on OXPHOS and a conductor for several other very important metabolic pathways. There are 13 known MEPAN patients in the world today, spanning three different continents. The disorder is passed on in an autosomal recessive manner, meaning a patient inherits a copy of a faulty gene from each parent. MEPAN may be more prevalent among Ashkenazi Jews, as five of the first seven MEPAN families shared some Jewish heritage. MEPAN patients have trouble with movement, coordination and balance, have trouble speaking, and can be wheelchair-bound. More patients with MECR mutations and other mtFAS defects are certain to be found, as researchers gain a better understanding of the genes involved in mtFAS and its significance to other complexes within the cellular and mitochondrial architectures.

Headquarters: Corte Madera, California

How did you become involved in rare disease: My boys were diagnosed with MEPAN syndrome in February of last year. That was the culmination of five years of research, genetic testing, lots of sleepless nights, and contacting doctors, clinicians, and researchers who might help us figure out what was going on with our boys. Initially, our oldest son, who was born in 2011, was diagnosed with cerebral palsy when he was about 14 months old. Around that time, we had our second son, Chase, and seven or eight months into his development we started to see some of the same things—developmental delays and he wasn’t quite moving the way other kids did. We began to suspect an underlying genetic condition. MEPAN and the MECR mutation was not known to be pathogenic until the one and only paper was published in 2016. It was around that time that we were admitted into the NIH undiagnosed disease program. They did a complete work-up. We had our whole genome sequenced and by that time, the MECR mutation and MEPAN had filtered down into the literature a little bit. They discovered that my boys had that MECR mutation. And we had that diagnosis in February last year.

Career: I am a communications consultant to biotech companies.

Education: B.A. in history from the University of Florida

The Organization
Organization’s mission: Given that there isn’t a lot of awareness around MEPAN syndrome and that there’s no way to diagnose the condition other than by having whole exome or whole genome sequencing, we believe that there are many more patients to be found. Because it presents with neurological symptoms—dystonia, ataxia, someone might be diagnosed with juvenile Parkinson’s—there are more patients out there who are undiagnosed. Our primary focus right now is on raising awareness for MEPAN syndrome, as well as mitochondrial fatty acid synthesis because there are half a dozen other genes in the pathway that are not well studied. Patients with mutations in those genes have a similar presentation to my boys. There’s an understudied pathway here that research is beginning to show is very important to our biological development, cellular homeostasis, and mitochondrial health and function.

Organization’s strategy: We are reaching out to all of the companies that are doing genetic testing and genetic screening and sharing with them information about MEPAN syndrome and sharing with them the gene review that was just published within the last month that discusses the condition and its prevalence. There seems to be an affinity, or a predisposition for it in the Ashkenazi Jewish population. I think it’s a disease that merits consideration for adding to screening for Jewish genetic conditions like Tay-Sachs and Canavan disease. More broadly, we are reaching out to child neurologists and different organizations that may have MEPAN patients who are misdiagnosed—medical research foundations, national ataxia organizations, Parkinson’s organizations—that may have a patient who has been misdiagnosed. There are more patients out there.

Funding strategy: Right now, we’re focusing on family and friends. We are also in talks with the National Institutes of Health to get some pilot projects going. We hope to leverage some of the NIH funding vehicles that are available. The NIH and some of their organizations are becoming much more receptive to devoting resources and funds to conditions to these conditions that were really sort of an afterthought. The work of parents and advocacy organizations have pushed them to focus more on the rare. They are becoming more comfortable with the notion that rare informs the common.

What’s changing at your organization in the next year: We’re going to continue building up our scientific board and corporate board and we are going to get our first research project off the ground. The awareness is great, but once we get past the awareness stage in the next six to nine months, we are going to be developing programs, whether its natural histories, drug screening assays, small molecule drugs, and even gene therapies that may help MEPAN patients.

Management Style
Management philosophy: I think it’s more of a laissez-faire approach. It is to let your people do what they do best, leverage their strengths, and take a team approach. In my few years of doing this and finding that there are many different silos and many competing interests. There’s almost a balkanization if you will. There’s strength in numbers. If you can get past some of the differences that you might have with another person or organization, you can accomplish much more.

Guiding principles for running an effective organization: Open lines of communication are essential. If you are communicating up front and quickly, you can avoid problems.

Best way to keep your organization relevant: Showing up and being involved in anything that you can. It’s possible to over extend yourself of course, but I think just showing up, being available, being involved, and participating in the conversation in any form that you can, whether it’s going to a conference or having a face-to-face meeting; these are still the best way to network, get to know the researchers that you need to be in touch with, and connect with the families to get commitments and convey passion. We’ll do that in person. There’s only so much you can do online or by email or phone. And tell your story to as many people as you can because you never know, either now or somewhere down the road, when that connection helps you or helps someone who comes behind you.

Why people like working with you: I’m passionate. I’m committed. I try to be knowledgeable about what I’m talking about. I’m also fun—I’m as fun as I can be in a situation like this where you are talking about quality of life, and in some cases about end of life in some of these conditions. This is serious stuff, but you have to have a sense of humor about some of this. You have to enjoy your successes. Live in the moment and cherish each day because you don’t know if the next one will come.

Mentor: I have lots of mentors. If you are talking about rare disease, many of the folks who came before me – Tracy VanHoutan in Batten disease and Matt Might with NGLY1. I’ve had the opportunity to connect with and learn from both of them. These are the real pioneers. It’s only in the last ten years that families have been able to band together with the Internet and social media to try to create awareness and connect with researchers. That wasn’t possible ten or 20 years ago, and the knowledge of genetic disease wasn’t there either. I try to learn from all of those folks who have come before me and who have done it and are doing it.

On the Job
What inspires you: My kids inspire me. Every day, when we go in to get them out of bed and get them ready for school, it’s like Christmas because they always have smiles on their faces, and they are always happy. That’s all you can ask for as a parent. My mom used to say, “You are only as happy as your unhappiest child.” If that’s the barometer, then I’m pretty happy because my kids are really happy despite all of the challenges they have. They are an inspiration to me and I’d like to think that they are an inspiration to people around them, not only people with rare disease, but also to people who aren’t affected by rare disease because they can show you how to go about living life with a smile and having a zest for life that many people just walking and talking aren’t able to enjoy.

What makes you hopeful: There are so many exciting things happening with therapies and treatments for rare diseases—gene therapy, antisense oligonucleotides therapies, enzyme replacement therapies. Much work is being done in these areas. There’s hope for anyone with a monogenic disease. If you restore that gene function, replace that gene, or develop a small molecule therapy—there’re many different options. As the understanding of these therapies, how they work, and how to treat these patients become more mainstream, the cost is going to come down and they’ll become more available.

Best organization decision: I think forming the MEPAN Foundation was the best decision. There are other mitochondrial disease organizations, but I felt passionate about starting the MEPAN foundation to focus on this particular gene, this particular pathway, which I feel is understudied and merits more scrutiny. I’d never done anything like this in my whole life. I’ve had some professional successes. I’ve been able to advance my career. But this is by far the richest, most rewarding, and toughest experience that I’ve ever undertaken. This is not just for my kids, but for others who follow behind us.

Hardest lesson learned: I just went on and on about how wonderful it is that there are these advances in gene therapies and things, and the treatments that will be available, but they take time and there are regulatory steps involved. There’s funding that’s needed, science that has to happen, and good science takes time. It’s tough to hurry up and wait when you’ve got a family member, friend, or someone suffering from a rare disease. Many times, they can’t wait. These are fatal conditions we’re talking about. It doesn’t seem to be that MEPAN is a fatal condition, but who’s to say that the boys won’t have some sort of relapse or setback, and I don’t want to see that happen. I want to do everything I can to try to find things that will help them, but it does take time.

Toughest organization decision: For me, it’s around fundraising. In many cases you can’t get anything going without access to funds that you can provide to researchers to pursue your gene or your disease. As someone who has been pretty self-reliant, it’s tough for me to go out and ask for money. It’s not something I enjoy doing, but its an absolute necessity.

Biggest missed opportunity: I wish there were three of me to follow up on every lead that I get when I talk to a researcher, a fellow rare disease advocate, or a clinician who has a suggestion for how to approach the science and research. I wish there were three more Danny Millers to get all the things that need to get done. I don’t think I’ve missed any of these opportunities, I just wish I could get to them faster.

Like best about the job: I’m helping to advance a broader cause. I’m trying to help my sons be the best they can be, and having come into contact with so many other families where we all share the same experience and are all dedicated and willing to go to great lengths to do anything to help our kids and our families. Being that mission driven and having that personal connection shared across all 7,000 rare diseases is pretty amazing and it’s something I cherish.

Like least about the job: Fundraising

Pet peeve: People who are not willing to listen. You come into contact with many researchers, doctors, and clinicians. It doesn’t happen often, but sometimes they don’t listen. Listening is a very underrated skill—the ability to listen and understand and empathize. Being in a room with someone who isn’t willing to listen is pretty frustrating.

First choice for a new career: I’d probably be a biochemist. I’ve been accused of being a biochemist in conversations with doctors and researchers. It’s a compliment, but I wish I didn’t have to know and learn so much about biochemistry and biology and those kinds of things. If I had to do it again, I think it’s clear that I might be pretty good at it.

Personal Taste
Most influential book: The Big Book of Alcoholics Anonymous by Bill Wilson and Aaron Cohen. I am in recovery. I think being in recovery has prepared me emotionally and given me the strength and the courage to do everything I can to help them and accept them for who they are.

Favorite movie: The Godfather

Favorite music: ‘90s alternative

Favorite food: Italian

Guilty pleasure: Ice cream

Favorite way to spend free time: I love spending time with my sons and taking care of myself. My wife and I are super busy caring for our kids and making sure their needs are met. I know a great way for me to spend my free time is to take care of me, whether its spiritually, physically, or emotionally. If I am not taking care of myself, I’m not going to be able to show up for my kids.