TODAY is Kentucky Gives Day, an online 24-hour annual fundraising event bringing charities and Kentuckians—near and far—together for a powerful day of action.
Last year, the NUBPL Foundation won 2nd place overall for most funds raised in 24 hours. Impressive! With your donation TODAY, we aim to win 1st place and win an additional $1,500 for research. In case you missed it, here’s an in-depth article from The Pennsylvania Gazette about the critical research you are supporting.
Research dollars are difficult to come by for rare diseases, and your generous donation goes a long way toward helping us meet our goals. NUBPL is a progressive disease with zero FDA approved treatments. Once the brain cells have died, there is no bringing them back.
We are racing against time to save our children.
As the parents of a six-year old affected by this devastating disease, we cannot thank you enough for supporting our cause and helping keep hope alive for her future. Thank you!
A special thank you to The Pennsylvania Gazette for the feature cover story about how our family’s journey through the realm of rare disease led us to the newest frontier of precision genetic medicine at the Children’s Hospital of Philadelphia.
Here’s a short video of Katherine’s walking progress since March 2017. We will keep you updated with any future progress. As for a medical update, she started the extension phase of the EPI-743 clinical trial in February 2017. She’s scheduled for another MRI in October to find out if the atrophy of her cerebellum continues to worsen. Your prayers are appreciated.
For the past few years we have given an annual update in December, but so much has happened in the last few months that we want to share with you today.
Many of you have been on this journey with us since the very beginning when we started this blog in January 2014 after learning that Katherine had a rare disease that affected her cerebellum. In those early days, this blog was an outlet for our immense grief after being told by two doctors that our daughter had a quickly fatal disease.
It is soul-crushing.
Slowly, we made our way to research, awareness, advocacy, and thankfully, in February 2015, an accurate diagnosis of Mitochondrial Complex 1 Deficiency (NUBPL gene).
The only word we’ve found that best describes the last four years is journey. On this journey, we have learned that adaptability to change is key to moving forward. I am proud of what we’ve learned and accomplished amidst very difficult circumstances. I am also thankful for each of you who’ve followed along and continue to cheer for our daughter while lifting us up on our darkest days. You are an integral part of our story.
From the beginning, we knew that we needed to be Katherine’s voice in order to give her hope for the future. Isn’t that what we all want for our children? Sometimes that means something more or different depending on the circumstances. In our case, the task at hand – our greatest hope of all – is to give our child a treatment and cure for a disease that threatens to take her life sooner than any parent should have to imagine.
If someone is threatening to kill your child, most parents wouldn’t ignore the threat. I believe that most would try to prevent it – to go above and beyond to protect the life and well-being of their child. Mitochondrial Disease is threatening our daughter’s life and we have to stop it. We are on a mission to find a treatment and cure.
2017 Bi-Annual Report
1. Founded the NUBPL Foundation, Inc. to raise awareness and funding for Mitochondrial Complex 1 Deficiency (NUBPL gene).
2) In February we had our first fundraiser, Rare Bourbon for Rare Disease. The event grossed $32,000. There is a nice write-up about the event here: The Spirit of Giving, Paducah Life Magazine
3) Traveled to California to meet another NUBPL family (The Spooner Family) at UC-Irvine – first time two NUBPL families have ever met. We met with Dr. Virginia Kimonos and other mitochondrial disease researchers at UC-Irvine and toured their lab.
4) I continue to write advocacy articles for The Mighty Publication and we hope to participate in a legislative advocacy webinar in the coming months to help others advocate for Mitochondrial Disease legislation. My latest article for The Mighty is here.
5) We are growing our NUBPL community and are now in contact with another family in Canada and will meet another one in two weeks – the first non-sibling match to our daughter in the world. The more families we can connect with, the more we can learn from one another and fundraise for treatments together.
6) In April we participated in 2017 Kentucky Gives Day and received the second highest donations in the state, netting $10,565 (and receiving $1,000 for second place). 7) Katherine entered the extension phase of the EPI-743 trial and continues on the drug today. We made several trips to the NIH and presented our journey to attending NIH physicians.
8) In June we with researchers at the Mitochondrial-Genetic Disease Clinic at the Children’s Hospital of Philadelphia (CHOP) and toured their laboratory.
At this point on our journey, we are tackling the daunting challenge of major fundraising. Ideally, we would like to fund all NUBPL research, but at this point we feel the best approach is to research the natural history of NUBPL and to do so as quickly as possible so that a therapy can be determined to help Katherine.
Every donation matters and is greatly appreciated. Every donation is tax-deductible. Every donation advances critical mitochondrial disease research that will help not just Katherine but countless others. The approach being used will test many strategies that are hoped to be used for other mitochondrial diseases. The natural history studies are necessary to set a baseline against which they can measure the efficacy of the therapies, which show promise across mitochondrial diseases.
We whole-heartedly believe in this research and will keep moving forward to give Katherine and others affected by this disease the best chance at life. We hope you will continue to walk with us as we venture into this critical aspect of our journey. We’ve come so far in four short years; I truly believe that, together, we can fund a treatment.
A little over two years ago, we received Katherine’s results for Whole Exome Sequencing (WES), giving us a name, NUBPL, to the disease that was a mystery to her doctors and is responsible for the atrophy of her cerebellum. Although we finally knew the name of the mutated gene, and that it was considered a rare form of Mitochondrial Complex 1 Deficiency, we didn’t know much more than that. In fact, at the time we quickly learned that her disease was recently discovered.
Although we were elated to receive a diagnosis, we realized that we didn’t know how the disease would affect Katherine’s life. Her doctor had never seen another patient with NUBPL, so he didn’t have much to tell us in terms of disease progression.
We searched the Internet looking for any information we could find, which included a couple of scientific articles citing six patients from 5 unrelated families. From these articles, we learned more about the patients, including sex, age, country of origin, clinical signs, MRI details, when and if they walked independently, and cognitive function. We had no way of contacting any of these families without knowing their names or doctors. We didn’t even have a photograph.
I felt like a detective scouring the Internet hoping to find a clue. I started tagging everything we shared with “NUBPL” and searched the Internet several times a day for a signal from anyone out there who had this disease. I posted in Facebook groups and wrote blog posts, anything I could think of that might put us in contact with another family with this same disease.
Just a few weeks later, I was looking through posts on the Global Genes Facebook page when I noticed a post from a mom sharing a link to a documentary about their 14-year journey to a diagnosis for both her daughters who were diagnosed with NUBPL. As I watched the documentary, tears rolled down my face as I picked up the phone to call Dave to tell him I’d found another family. And that they looked happy and one was walking independently. After living with a misdiagnosis for nearly two years of a quickly fatal disease, I’ll never forget the moment that I saw the smiling face of a 16-year old girl with same disease as Katherine.
Everything is about perspective in this life. After being told that my child was going to die by the age of seven, that first glimpse at Cali Spooner’s face added years to my child’s life. In her photograph I saw Katherine smiling back at the camera. For the first time, I saw Katherine as a teenager.
And then I saw Ryaan Spooner’s face and recognized my Katherine in her as well. And she could walk independently. Their body types were even similar.
The Spooner Family
I got off the phone with Dave and contacted their mom, Cristy, who responded immediately and we’ve been in contact ever since. She put us in touch with their doctor at UC-Irvine, Dr. Virginia Kimonis, who was growing fibroblasts to learn more about the disease. We contacted Dr. Kimonis and sent Katherine’s skin biopsy for research.
Last week, our family traveled to California to attend the first NUBPL Family Conference at UC-Irvine and to spend time with the Spooner Family.
We heard from several researchers and toured the lab where they have been growing our daughter’s fibroblasts.
And a few days later, we were able to introduce our girls to one another for the very first time.
Both of our families instantly hit it off as we watched our girls play together. We were all sad that the night had to end and we had to go back to living on opposite coasts.
Katherine and Ryaan share a love of dolls and both are fiercely determined and independent. They are very similar in many ways. Katherine watched Ryaan walk independently, which she learned to do at Katherine’s age (they are two years apart). After seeing Ryaan walking, Katherine is now determined more than ever that she’s going to do the same. And I know she will.
Our girls are three of 11 NUBPL patients identified in the world. After spending time with The Spooner Family, I am reassured more than ever that we will find more NUBPL families in the future. These things take time and we are just getting started.
We are two families brought together through science, hope, love, and a fierce determination to give our girls the best chance possible at life. Where science hasn’t caught up, we will fund the research ourselves through our non-profits. Where there are barriers to diagnosing more patients in the future, we will spend our time to eliminate those barriers. And when we cannot find those patients as they are diagnosed, we will do everything we can to make sure they can find us.
As our families were spending time together in California, a mom with two daughters made contact with both of us. Yes, I am hopeful that we will grow our NUBPL community.
Last year we founded the NUBPL Foundation to elevate NUBPL awareness and research. In February 2015, our daughter was diagnosed with a recently discovered form of Mitochondrial disease named after the affected nuclear gene, nucleotide-binding protein-like (NUBPL). As one of 11 identified patients in the world, research is needed to understand more about this disease.
This is an exciting time for our family as we expand our rare disease journey to grow NUBPL’s patient population and fund research and, hopefully, develop a treatment or cures.
We had our first fundraiser at the Haymarket Whiskey Bar in Louisville, Kentucky, on February 25, 2017. Our foundation was selected as one of 200 charities to receive a bottle of Buffalo Trace O.F.C. Vintage Collection, an estimated value of $10,000 per bottle.
Coordinated by Dave’s cousin, Brian Shemwell, founder and president of the Paducah Bourbon Society, Haymarket Whiskey Bar, Masonic Homes of Kentucky (event food sponsor), and five regional bourbon societies – Louisville, Paducah, Owensboro and Lexington Bourbon Societies and JB’s Whiskey House of Nashville – came together under one umbrella to support our cause, raising a total of $32,000 in ONE night for the NUBPL Foundation from rare bourbon tastings and silent auction items.
Dave and I were blown away by the level of support we received from event sponsors and attendees. As Dave concluded his speech about our rare disease journey and the NUBPL Foundation, he concluded with these words:
“Whiskey is a Celtic word meaning ‘water of life’ and it’s never been more fitting than this moment. Tonight we raise our glasses of whiskey to save a life. To life.”
Unbeknownst to me when I ordered it, this birthday crown is clever and cost efficient. Instead of buying a new one every year, I can use the same one and just add a new number…you get the idea. Unfortunately, this little crown brought so many tears. Will she get to use every number? Please let her use all of these numbers.
Looking back, we realize that every prior birthday has greeted us with worries. By her first birthday, we knew something was wrong; our expectation that she would walk prior to turning one proved untrue and her motor development had stalled. Our nagging worry at one was a gut wrenching terror by two; she still was not walking. On her third birthday, we were living under a death sentence and the day was a bittersweet reminder that we probably had few such occasions left…Today, we have a new – an accurate – diagnosis, NUBPL, Mitochondrial Complex 1, and a new hope. This is a happy day and one of many more to come.
As I carefully placed those five pink and purple candles on top of her cake, a sense of relief washed over me. The haunting statistic that “30% of children with rare and genetic diseases will not live to see their fifth birthday” is now behind us. Yes, there are many struggles ahead, but it’s an indescribable moment to see those happy and beautiful sparkling eyes glowing in the light of five birthday candles.
Soon after Katherine’s (mis) diagnosis in 2013, I wrote the following:
I do not know what tomorrow brings. None of us do. I believe in science, prayers, hard work, positive thought, and the healing power of love. Each day I share my photographs with friends and family and tell them a story that does not always require words, and that sometimes cannot be expressed with them. It is a story of faith, hope, love, and determination. As we continue ahead on our journey toward a diagnosis, I see a brave and thriving girl who is progressing, not regressing. I see a happy and joyful child who meets every obstacle or challenge with the biggest smile and the most positive attitude. I see a future with many more photographs of accomplishments, milestones, and laughter. In all of my pictures, I see faith, hope and love. Above all, I see an abundance of love.
I have cried many tears in the last three years from witnessing the physical decline and death of numerous children with rare diseases we’ve met through social media. Instead of planning birthday party celebrations and school graduations, I have watched families plan funerals and suffer more than any human ever should.
As we continue ahead beyond this fifth birthday milestone, my own words lead me into the next chapter:
The past few years have been excruciatingly painful and tough, but I have learned a very valuable lesson: You never know what the next second of your life will bring. My daughter guides me daily and reminds me that each moment is precious. Each day is a gift. She has taught me the significance of the quote, “We do not remember days, we remember moments.” I have learned to enjoy and live in the present because it truly is the only moment that matters.
Gene Name: NUBPL, acronym for Nucleotide-binding protein-like
Also Known As: Iron-sulfur protein required for NADH dehydrogenase or IND1
Location: Chromosome 14q12
Symbols: NUBPL; IND1; huInd1; C14orf127
Genetic Inheritance: Recessive
Gene Function: It is an iron-sulfur (Fe/S) protein that, in humans, is encoded by the NUBPL gene. It that has an early role in the assembly of the mitochondrial complex I assembly pathway.
Mutations in the NUBPL gene may cause a rare form of mitochondrial complex I disorder.
Typical clinical signs and symptoms:
Age of onset 1-2 years old
Developmental delay: Some patients
Delay: Motor; Unable to walk
Speech: Abnormal (Dysarthria)
Eyes: Strabismus; Nystagmus
Ataxia: Trunk & Limbs
Contractures
Spasticity
Cognitive: Normal or Reduced
Myopathy
Other organs: Normal
Course: Progressive, continuous or episodic
Laboratory signs:
MRI: Leukoencephalopathy with abnormal:
Cerebellar cortex: Progressive
Cerebral white matter, deep: May resolve
Corpus callosum: May resolve
*Although these are characteristic MRI findings, there are others including abnormalities in the grey matter of the cerebellum, as is discussed in Hope for Katherine Belle.
Lactate: Serum normal or high; CSF normal or high
NUBPL protein: Reduced
Muscle biopsy
Histology: Ragged red fibers; No COX- fibers
Biochemistry: Complex I deficiency
Overview of NUBPL Mutations
GeneDx (USA): c.166G>A (maternal); c.815-27T>A (maternal); and c.693+1G>A (paternal)
Sheftel, A. “Human ind1, an iron-sulfur cluster assembly factor for respiratory complex I”. Mol. Cell. Biol.29 (22): 6059–6073. PMID19752196.
Calvo, S. “High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency”. PMID20818383.
Kevelam, S. “NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern”. Neurology80 (17): 1577–1583. PMID23553477
The more we connect with other NUBPL families, the closer we get to finding a cure. Do you have NUBPL or do you think you may? Or, are you a researcher who is interested in studying NUBPL? Please contact us. We want to hear from you. Although some families are public about their journey, we respect your desire for privacy.
I like a challenge, especially when the challenge is for a good cause. What is #Hope4KB?
#Hope4KB is a T-shirt campaign designed to raise awareness for rare diseases around the world through social media (KB is our daughter, Katherine Belle, a three-year-old from Lexington, KY, who is battling an unknown, progressive rare disease);
You purchase your #HopeforKB shirt from Print My Threads here;
Orders will be collected through March 1st. Wear on Rare Disease Day on February 28, 2015 (only orders placed by February 18th will arrive for Rare Disease Day, but we want you to wear this shirt all the time!) ;
Take a picture of yourself and/or family and friends wearing your #Hope4KB shirt and share it on your social media accounts, i.e. Facebook, Instagram, Twitter, etc. with #Hope4KB; and
The goal is to BREAK. THE. INTERNET.
Ellen did it. Kim Kardashian did it. It happened with the ALS #IceBucketChallenge – Let’s do it with #Hope4KB! Not to mention these are the softest, most comfortable American Apparel tri-blend short sleeve track shirts. Trust me, you’ll be wearing this shirt LONG after February 28, 2015. (Psst…you can still help even if you don’t have any social media accounts – this campaign is for everybody! Simply take a picture and send it to me at gcmccoy1@aol.com and I’ll make sure it’s shared!) *Proceeds will benefit Katherine Belle and Katie Webb Kneisley. (Click here to read her story.)
Katherine gave us a big scare last Saturday when she had what we (and two neurologists) think was a seizure. After a four day stay at the University of Kentucky Children’s Hospital and a two-day EEG video, she is now on seizure medication.
We are so happy to be home to celebrate Christmas. We made our annual Christmas cookies and ate them under the tree.
We are doing our best to make this Christmas as magical as possible for Katherine.
We do not have a P.O. Box established to receive cards or gifts.
We have asked that you please refrain from sending presents. We are trying to sell our home and I can assure you that KB has more than enough. If you want to help our family, we ask that you please make a donation to www.gofundme.com/hopeforkatherinebelle to help pay for medical expenses, testing, etc.
I have a bag of duplicate toys she’s received – yes, a bag a them! – ready to take to a toy drive.
If this isn’t something you want to do, then please donate a toy to a local charity, or donate to Rare Disease United Foundation, or Global Genes Project. Or share our story and help us raise awareness.
Also, please consider sending a card to sweet Addie. She has an unknown rare disease and loves Christmas cards.
Finally, if we could we would send each of you a Christmas card. Instead, please accept this card as a token of our love and appreciation for each of you. Thank you for following our story, for helping us raise awareness for rare disease, and for listening to and sharing our fears, our triumphs, our sorrows.
We are so grateful for the many generous donations you have made to help us fund this diagnostic odyssey. Mostly, we appreciate your prayers, kind hearts, and for loving a child you’ve never met, but want to help and pray for on a daily basis. You give us more comfort and hope than you may realize.
We truly believe that no matter what may come, we can all rejoice in knowing the world is a better place because of children like Katherine Belle.
From the bottom of our hearts, we wish each of you a very Merry Christmas!
Every day on my way to and from work, I pass Boot Hill Farm in Clark County, the former home of Rena and John Jacob Niles. John Jacob was a man of many talents. He was a singer and a songwriter, crafted musical instruments and was an author. He is known as the “Dean of American Balladeers” and the Center for American Music at the University of Kentucky is named after him.
Their house on Boot Hill Farm is a veritable rabbit warren of contrasting styles and materials, with no apparent rhyme or reason for numerous additions. Yet, somehow, the lack of cohesive design causes the house, out buildings and farm to strike my imagination. It gives Boot Hill a feeling of whimsy. It is as if there is a method to this madness.
In 1947, Rena and John Jacob published an illustrated children’s book titled Mr. Poof’s Discovery, in which the title character, a mouse, made a discovery about cream. This story was modified and paraphrased in the movie Catch Me If You Can. The movie version was told as follows:
(Frank Abagnale, Sr.): Two little mice fell in a bucket of cream. The first mouse quickly gave up and drowned. The second mouse wouldn’t quit. He struggled so hard that eventually he churned that cream into butter and crawled out. Gentlemen, as of this moment, I am that second mouse.
To our readers affected by rare disease, or anyone else facing what seem to be hopeless circumstances or insurmountable obstacles, this story is a wonderful reminder why you should always keep churning.
No big surprise, but I am constantly struggling to find balance in my life. As a caregiver who is navigating the rare disease world and ALL that entails, it is hard to find much time for myself (or to cook dinner for that matter).
I spend my days trying to keep Katherine’s little hands and feet as busy as possible, which is challenging for a child who cannot walk, lacks balance, and struggles with speech and fine motor skills. Needless to say, I haven’t had much spare time to post lately, so I want to share some pictures of our fall here in Kentucky. As you will see from the photographs, Katherine is happy and loving our daily projects and adventures.
Also, our friend David Wheeler wrote a wonderful article about our family for The Motherlode blog in The New York Times – “When the Diagnosis is Rare, Parents May Know More Than Professionals.” I encourage each of you to read it and share. Thank you David for writing this important story. We hope it will empower others in the rare disease community.
This article in the New Yorker is by far the most important article we’ve read to date that defines our purpose and hope for Katherine Belle. Thanks to the Mights and Wilseys for confirming what we hope to achieve and proving there are other options than just waiting and hoping science “catches up.” When parents are given no other option but to create websites and post articles with their genetic data to accelerate research and treatments for our dying children, there is a serious problem with the system. We are an important part of the diagnostic team and can play a critical role in helping decipher the human genome. My question is why aren’t more journalists talking about this problem?
Matt Might gave a talk titled “Accelerating Rare Disease.” After describing the effects of his blog post, he told the crowd that it was inevitable that parents of children with other newly discovered diseases would form proactive communities, much as he, Cristina, and the Wilseys had done. Vandana Shashi believes that such communities represent a new paradigm for conducting medical research. “It’s kind of a shift in the scientific world that we have to recognize—that, in this day of social media, dedicated, educated, and well-informed families have the ability to make a huge impact,” she told me. “Gone are the days when we could just say, ‘We’re a cloistered community of researchers, and we alone know how to do this.’
7) Katherine entered the extension phase of the EPI-743 trial and continues on the drug today. We made several trips to the NIH and presented our journey to attending NIH physicians.
HOPE FOR KATHERINE BELLE 