October 1st, 2024

“Just say hello!  She’s really nice!”  Our mutual friends had been trying to get me to introduce myself to Beth McGinn for months since I discovered our unusual connection.  While casually flipping through our neighborhood newsletter — in between real estate ads and updates on invasive plants from the gardening committee — was a notice about an upcoming 5K.  The race was organized by A Cure For Ellie, a local non-profit funding research at the Kennedy Krieger Institute for a rare leukodystrophy called LBSL.  Beth and her husband Mike started the foundation to help their daughter, Ellie — a bright-eyed girl who shared my daughter’s name and attended the same elementary school.  The world-famous research center they were funding was where our family had turned for answers, too.  My heart sank.   

I knew the word leukodystrophy, and in my personal experience and research, it didn’t end well.  Apart from my brother, I had never met anyone with a leukodystrophy.  I’m not sure if I had even met anyone who had heard that awful word.  Part of me wanted to run up and hug Beth and scream “I know that word!  Our family goes to Kennedy Krieger!  I’ll help you!”  But I was too scared.  I knew Beth’s world had been flipped upside down by that horrible diagnosis, and the last thing she wanted was for someone to come up and say “Hi!  I’m Melody.  My brother died from a leukodystrophy.  Do you want to be my friend?”  (I’m not quite that socially challenged, but awkward enough that I feared anything that came out of my mouth would be an unwelcome burden on top of the unimaginable weight that she was already carrying).  I hesitated and then retreated, going home to squeeze my children extra tight, as one does after a reminder of how fragile life can be.  Months later, I was literally shoved into her by a mutual friend who was tired of my stalling tactics and forced the introduction.  “Melody, this is Beth.  Beth this is Melody.”   

Over the years, Beth and I stayed in touch.  Our family, along with the rest of the neighborhood, cheerfully showed up to support the annual 5K and silent auction to benefit A Cure for Ellie (now Cure LBSL).  We opened our hearts and our wallets on Giving Tuesday, and we smiled warmly when Ellie would come out of school with her signature pink protective helmet.  Our community rallied around the McGinns, and we witnessed firsthand the power of a grassroots effort.  Never – NEVER – underestimate the power of a motivated mother trying to save her child.  (Or a motivated aunt fighting for her nieces and nephews!)  

After years of supporting the 5K and donating whenever I could to the LBSL cause, Beth reached out one day to let me know that their foundation had been awarded an incredibly generous Rare as One grant from the Chan Zuckerburg Initiative (CZI).  It was a capacity building grant which would allow them to bring on staff to help expand advocacy efforts to a global community.  Since I had a degree in bioethics and worked in public health, she was calling to ask if I knew anyone in my network who might be interested in the role.  Why, yes I did!  ME!  By the end of the week, I was their new Director of Patient Engagement, a job that has been the most personally and professionally gratifying role of my career.   

Despite being a supporter of the LBSL cause for many years, it wasn’t until I started the job that I learned how LBSL is both similar and different from other leukodystrophies.  From a very successful publicity campaign that landed them on the Today Show, I already knew that LBSL stands for Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation.  What I didn’t know is that while leukodystrophies all have white matter changes, they can have very different biological causes.  Caused by two pathogenic variants on the DARS2 gene, LBSL is considered both a mitochondrial disorder and a leukodystrophy.  People with LBSL have many symptoms in common with other mitochondrial disorders — severe energy deficits, crippling fatigue, heat intolerance, etc.  Symptoms also overlap with leukodystrophies – ataxia, balance / coordination, gait disturbances, fine motor difficulties, speech challenges, etc.  Triggers — such as fever, infection, overheating, anesthesia, and minor head injuries — can cause severe regressions which are sometimes irreversible.   

LBSL often shows up in early childhood, although some more severely-affected children are born with symptoms that developed prenatally.  There may also be a milder adult-onset form, although with careful retrospective review of medical history, it’s looks like many of those people had evidence of LBSL earlier in life, and more accurately have an “adult-diagnosis” rather than an “adult-onset” disorder.  Like with ALSP, adults who develop symptoms are often misdiagnosed as having MS, Friedreich’s Ataxia, or other related neurodegenerative disorders.  Unlike many of the other leukodystrophies, LBSL is not uniformly fatal, although tragically about 25% of people with infantile-onset LBSL do pass away in from irretractable seizures, respiratory failure, or metabolic decompensation. Most people with LBSL live with varying degrees of progressive neurological decline, often affecting mobility and balance more than cognition and communication.   

The generous funding from the CZI grant allowed me to attend many conference, networking with other rare disease advocates, spreading awareness about LBSL, and collecting resources to bring back to the community.  One such conference was lifechanging! 

I was at the Rare Drug Development Symposium in Philadelphia in May of 2023 – an outstanding conference co-sponsored by Global Genes and the Orphan Disease Center.  There were several choices for breakout sessions, and I fortuitously chose the one with Dr. David Fajgenbaum, where he spoke about his upcoming Every Cure drug repurposing platform.  Perhaps if I had known what a celebrity he was, I might have been more intimidated, but he was down to earth and approachable. I raised my hand an asked a question about the platform, and mentioned that I represent a disorder that is both mitochondrial and a leukodystrophy.  The universe (or whatever higher power you believe in) must have brought me there that day and opened my mouth to ask that question, because in the same room was Cynthia Cassandro from Vigil Neuroscience.  Cynthia warmly approached me after the breakout to share that her pharmaceutical company works on an adult-onset leukodystrophy called ALSP.  I had never heard of ALSP, and until meeting her, had no idea that HDLS and POLD were historic names for the same disorder.  And I sure had no idea that the responsible gene – CSF1R – had been identified.  Most importantly, I had no idea that Sister’s Hope existed.  Cynthia introduced me to Heidi Edwards, and as they say, the rest was history.   

Since connecting with Cynthia and Heidi and Erin, our family has directly benefitted from the support and resources of the ALSP community.  We have taken advantage of the genetic testing and counseling through ALSPAware.  I have signed up to be the family ambassador – sharing information and resources with family members who could benefit from knowing about my brother’s likely diagnosis and their genetic risk.  It’s an uphill battle – not everyone wants to know, not everyone is ready to test, and not everyone can let go of decades-old misconceptions.  No, it wasn’t mad cow disease!   

It is truly an honor and privilege to work with the LBSL community every day, and to have the opportunity to work closely with other leukodystrophy groups like Sister’s Hope.  I am continually in awe of the rare disease warriors like Heidi and Erin and Beth, who channel their grief and fear and move mountains with their determination.  I am so grateful to have the “fire” of being an affected family member, without the daily challenge of taking care of someone with a leukodystrophy or other rare disease.   

That chance meeting in Philly has led to my new personal philosophy – one that I share regularly with the new leukodystrophy leaders who reach out to me for support.  “Show up!  Speak up!  You never know who you will meet and how that person will change your life.”   

Melody Kisor, MS 

Director of Patient Engagement for Cure LBSL 

Co-chair, Global Leukodystrophy Initiative Advocacy Committee 

ALSP sister / family ambassador