UMDF Mitochondrial Medicine 2018 Recap

Earlier this summer, I attended the Mitochondrial Medicine 2018 conference in Nashville. Hosted by the United Mitochondrial Disease Foundation (UMDF), the conference had attendees from almost every state in the US, and more than 15 countries around the world. A few days before, I was in Atlanta for the ML4 Foundation’s Family and Research conference. After two back-to-back rare disease conferences, in addition to many others over the past 5 years, I’ve come to see that every rare disease conference has two purposes: to replenish reservoirs of hope, and to drive dollars toward cures. The Mitochondrial Medicine 2018 conference was no exception.

Getting to Mitochondrial Medicine 2018

Rare disease is a people business. Relationships between stakeholders take months to years to develop, but start with a chance meeting or introduction. It’s also about seizing unexpected opportunities. For example, if this is the only rental available to get you out of Atlanta on I-75N before rush hour, you take it.

Fortuitously, I bumped into Vamsi Mootha at the hotel bar on the eve of Mitochondrial Medicine 2018. Vamsi is a professor at Harvard Medical School and a leading mitochondrial researcher. When I first met Vamsi, I was a grad student and he was a newly-minted assistant professor. In 2005 I would have never imagined us meeting at the Mitochondrial Medicine 2018 conference, and yet there we were.

This was my first UMDF meeting. And, like the ML4 meeting I had just attended – and like many of the relationships that led to PerlQuests – the path to that moment was made possible by a persistent champion. Phil Yeske, the CSO of UMDF, reached out to Perlara in January 2016, after reading a company profile in Popular Science. We kept in touch over the last two years as Perlstein Lab, the scrappy startup, transformed into Perlara, the growing biotech company. During that time, we proved out our novel patient advocacy group (PAG) partnership business model with our inaugural class of PerlQuests. I was eager to present our model organism-based drug discovery platform to the UMDF community of researchers and families, and equally eager to learn as much as I could about mitochondrial diseases from the perspectives of both researchers and families so that we could launch Mito PerlQuests together in the near future.

Vamsi kicked off Mitochondrial Medicine 2018. As I always do in support of open science, I live-tweeted talks (only clearly published results, of course.)

My live-tweeting partner in crime was patient advocate @DevinShuman. It was awesome to see Devin in action. I could quote all of her #mitomed18 tweets because she did a stellar job distilling complex science into tweets. I hope next year there will be more patient advocates like her live-tweeting.

What are Mito diseases?

Mitochondrial diseases are heterogenous by genotype, but relatively homogenous by phenotype, depending on age of onset. Over 150 mitochondrial disease genes have been identified. Not all of these genes reside in the nucleus. What separates Mito diseases from all other rare genetic diseases is that mutations in the compact 16,569 base-pair mitochondrial genome – referred to as “mtDNA” – cause disease as potently as nuclear-encoded Mito disease gene mutations.

Everyone remembers from high school biology that the mitochondria are the “powerhouses of the cell” and some may have heard of humanity’s shared ancestor Mitochondrial Eve, but not everyone remembers that the mtDNA encodes the same 13 protein-coding genes in most animals, excluding fungi. Mitochondria were once free-living bacteria. In the course of evolution, the ancestor of all eukaryotes entered into a complex biological partnership of sorts: in exchange for a warm, cozy place to stay, and a steady supply of glucose, mitochondria generate ATP by the boatloads for the host cell, thereby powering the cellular economy. Ultimately, mitochondria stopped making many of the proteins it made when living on its own – and these genes were lost or emigrated to the nuclear genome – but that obstinate gang of 13 remained behind. Mutations are blind assassins. No genome is safe, which is a genetic complication unique to Mito disease inheritance. It also means current gene therapy approaches are not feasible for mtDNA mutations, but cell therapy and small molecule therapies are options.

Scientific presentation highlights

Talks were a mix of basic science – we still don’t know what 20-25% of mitochondrial genes do! – academic drug discovery and clinical trial progress reports of either nutraceutical, diet interventions or a few rational therapeutic mechanisms. There was gap in what I would call preclinical translation and a narrowness of the preclinical pipeline, which isn’t that surprising given the dearth of animal models that aren’t mice, and given that we’re still driving in the dark when it comes to things like biomarkers.

Marni Falk and her lab at CHOP is filling that gap, and had a big presence on Day 2. Marni succinctly summarized the state of play in Mito diseases and what can be done that’s medically actionable today, not years from now. My talk was right before hers, and we both gave model organisms the due they deserve, which is not something that can be said for all rare disease researchers.

Phil Yeske closed out Day 2 of Mitochondrial Medicine 2018 with a presentation on UMDF funded projects. As we would learn later that evening, UMDF has certainly come a long way in terms of fundraising since it cut its first check (for $30,000) to a Mito researcher 20 years ago. Since 1996, UMDF has granted $12M in donations to fund Mito diseases research, and plans to raise a lot more in the years ahead.

Mito families

The families started to arrive on the end of Day 2. I confess I was a little disappointed that the families weren’t invited and encouraged to participate in the scientific sessions. I know it’s much harder to do that with a meeting and community this large, but I’m an unrelenting believer in “teaching up” to families. Economies of rare emerge when rare disease families willing to push the envelope link up with like-minded rare disease researchers.

On the evening of Day 3, there was Friday Night Banquet and Awards Ceremony to honor Chuck Mohan, who was stepping down as UMDF President after founding the organization with his wife in their home in Pittsburgh in 1996. On the one hand, I was not a witness or party to these collective memories, but I still felt like I belonged, because I’ve heard stories just like these in other rare disease communities. Three researchers concluded the tribute with a raw and sweet rendition of “Somewhere Over the Rainbow” by Israel Kamakawiwo’ole. The torch was passing to a new generation of leaders at UMDF, and to newly diagnosed Mito families raising armies of hope and science.

 

The last day of Mitochondrial Medicine 2018 featured a morning science session, but most of the activity was centered on family support panels and family networking happening in parallel and into the afternoon. In a side room off the main conference hall where the night before scientists were milling about posters, I joined a group of Leigh Syndrome families that had never met before seated in a circle. This informal gathering was organized by People Against Leigh Syndrome (PALS).

Everyone went around the room and told their story, from diagnostic odyssey to the present day. Some of the parents were at Mitochondrial Medicine 2018 with their children, others were left with caretakers. A beautiful baby boy who had just been diagnosed weeks before was there in a carrier next to his mom and her parents. Parents of an affected teenager shared anecdotes of small victories. Other parents spoke about their experiences with clinical trials and challenges with insurance. They may have had mutations in different genes, like ND1-MT or SURF1, but they all spoke the same language of hope. Together with researchers, these families working with the UMDF will make new discoveries and clinical advances in the year ahead.