As a rare disease leader, staying current with new developments in rare disease research and connecting with other rare disease groups or potential MEPAN collaborators is an important part of ensuring that MEPAN Foundation is on the right path.

Going to conferences is one way to do that. It offers opportunities to learn from experts, network with peers, and gain insights into innovative strategies for that will expedite the therapy development in rare diseases like MEPAN. Attending these events is a big challenge for me as a rare disease dad.

Despite the support and services that my wife Nikki has so deftly arranged for our family, the day-to-day caregiving for Carson and Chase still requires a lot of hands-on work. From getting them in and out of bed, transfers to and from wheelchairs, stretching tight muscles, feeding and bathing, and everything else in between. For me to be away for three or four days is a major undertaking that requires buy-in from Nikki, coordination with caregivers, and extra support from friends. It's no small feat.

Last year I attended Global Genes' 2024 RARE Drug Development Symposium in Philadelphia; the agenda was focused on empowering rare disease advocates with the knowledge and tools necessary to advance therapy development for their communities.

It was very reassuring to see presentations from several rare disease leaders that mirrored much of the approach and direction that MEPAN Foundation has taken, from development animal models of the disease to drug repurposing and a multi-pronged therapeutic approach that ensures "multiple shots on goal" that can potentially address disease symptoms. I also met with rare disease experts who provided additional guidance for MEPAN research direction, including:

• Jennifer Farmer, the CEO of the Friedreich's Ataxia Research Alliance (FARA)

• Juan Carlos López, founder of Haystack Science

• Betty Cabrera from the University of San Diego's Gene Therapy Initiative

• Ashley Winslow, CEO/CSO of Odylia Therapeutics

• Elizabeth Ottinger, Ph.D., and Richa Lomash, Ph.D., from NCATS

While in Philadelphia I also stopped by the Children’s Hospital of Philadelphia (CHOP) to drop off cookies for Dr. Debbie Murdock, the scientific director of the Center for Mitochondrial and Epigenomic Medicine at CHOP. Debbie has been involved in mitochodnrial research for over 20 years, and has led the development of a MEPAN mouse models that will be a good tool for doing rare disease research and testing potential therapies.

Debbie shared some retinal images of a MEPAN mouse and we did a quick tour around the lab and met some of her team. It was great to connect with Debbie and learn more about her research and the plans for the upcoming 2024 UMDF Symposium.

Debbie's work has been funded by another family whose daughter also has MEPAN and is allied closely with the United Mitochondrial Disease Foundation. Their support has enabled the development of the CHOP MEPAN mouse line, and Debbie should soon be publishing a paper describing the characteristics of the mice, which is a big step in better understanding MEPAN disease pathology.

Finally, I met with Dr. Matt Demczko, the Clinical Education Director / Inpatient Consult Director with Mitochondrial Medicine at CHOP. Matt is caring for two children with MEPAN, is exploring ideas for possible biomarkers for the condition and is the principle investigator for a clinical trial that will study the use of sirolimus (rapamycin) to treat patients with Leigh's syndrome.

There are case studies that have shown some potential for this intervention, but the results have been mixed, and a clinical trial by Aadi Bioscience I explored that was similar to Dr. Demczko's was withdrawn in 2022, so it will be interesting to see the results from the CHOP study. I think rapamycin may help, but it likely would only improve some aspects of Leigh's syndrome pathology, and those could be influenced by the individual genetic mutation that each patient has.

This was an excellent event that provided some degree of measurement for MEPAN Foundation's research efforts. We are on the right path, with more to come.