Jack Leonard, Family Story
My name is Jeff and my second child (Jack) was born 7 ½ pounds and 20 inches long in March 2000 through a full-term, normal pregnancy and delivery. The moment he was born Jack let out a screeching sound, stridor. The doctor quickly scoped his throat for any physical obstruction and calmly said “Take him home and bring him to my office on Monday (4 days later). I’ll scope his throat and that requires an automatic overnight stay”. As we celebrated his birth and held him that first day, I noticed how his eyes would circle around as if he was struggling to focus on me or objects in the room. His head would move to compensate for his nystagmus. No matter. I just thought he’s a newborn. Nothing could stop the joy of having my first son.
Four uneventful days later, we brought Jack to that ENT appointment and prepared for 1 overnight. We knew he wasn’t eating as well as his older sister did when she was first born, but we weren’t concerned yet. The ENT said he has some floppy throat cartilage and likened it to drinking through a straw that collapses instead of staying sturdy. “He’ll grow out of it” he said. During the routine overnight stay a nurse thought Jack’s breathing was not good even though there was no cyanosis. We battled a bit, but Jack was admitted to the ER for further testing. Then our lives bent sideways. We spent the next 19 days in 2 hospitals, including CHOP. Jack had tons of x-rays and blood tests, an echocardiogram, a head CT scan, a brain MRI, a barium swallow and chest x-ray, a PH reflux test, a spinal tap, a blood transfusion, a bronchoscopy and two laryngoscopies (not to mention being intubated for 13 days) and barely missed getting a tracheostomy ... only to conclude that his brain, heart, lungs, trachea and blood vessels are all normal. He had caught RSV in the hospital. Oh and he has vocal cord paresis. We took Jack home and prepared to live normal lives again.
[SIDE NOTE: Pelizaeus Merzbacher Disease and all leukodystrophies should be included in newborn screening. Several doctors missed the PMD clinical symptoms of stridor, nystagmus, laryngomalacia and vocal cord paresis. The expense and agony of many diagnostic tests could have been avoided.]
Then Jack simply failed to thrive. It was torture – did he have a silly vitamin deficiency? Am I supposed to give him something basic that can end his discomfort and allow him to grow? Three months later, I brought him to CHOP and was referred to Genetics. The department chief, Dr. K at the time made an impossible call. He said “I think Jack has Pelizaeus Merzbacher disease and we need to draw a blood sample and send it to a special Indiana lab for analysis”. I said “whatever disease you just said, how many patients have you seen?” To my horror, Dr. K started counting on his fingers and said “well in my 25 years of practice as a geneticist and neurologist, Jack would be my 9th PMD patient”. Jack’s blood went off to Indiana and I went home to scour the web. PMD was doom but everything I read matched Jack’s symptoms. The diagnosis was confirmed and the prognosis was death within the first year.
I quit my job, bought funeral plots and prepared to have the most festive, most awesome celebration of Jack’s life for the entire year. Jack was placed on hospice. We had all of the nasty little medicines in the home. And then … a year passed, two years passed … three … and he was kicked out of hospice . What helped the most to support Jack? We did a great job of regimenting his day and taking care of his symptoms (with medicine, love and around-the-clock attention). Jack could not walk, talk, roll over, hold his head up and barely had any gross motor control whatsoever … but he could smile and there’s something very peaceful about him. He can non-verbally communicate if you are willing to look and listen. We thumbed our noses at PMD and lived our best lives.
Besides his breathing issues through laryngomalacia and vocal cord paresis, Jack’s most serious early symptom was the seizures. They never registered on any EEG or sleep study but they were regular and started getting longer and more intense. HCP’s were stumped. Jack was scared and in pain. His face would contort and freeze and his eyes would twitch. He would start crying because he knew it was coming.
It was another PMD parent who told me about Tegretol (carbamazepine). That was the miracle drug Jack needed. He took it 3 times a day for 14 years. Sadly, it knocks him out 2-3 hours but he needs it or he will have seizures. He also could not take it on an empty stomach. He became primarily tube-fed. At 1 year old Jack was 11 lbs. 4 oz.
As more symptoms appeared, we regimented Jack’s day around the following medicines:
Zanaflex and a tiny dose of Valium for spasticity. Prilosec for acid stomach. Tegretol for seizures.
Not daily, but the slightest respiratory issues were treated with nebulizers, Albuterol or Pulmicort. Saliva/secretions are a constant battle that carry choking risk. He keeps his head tilted to the right because it’s the best position to maximize his airway. Miralax for motility.
Over the years, Jack developed severe scoliosis. He is too small to be a candidate for back surgery or to fix hip sockets.
I know patients with the classic form of PMD can live many decades. Patients like Jack with this conatal form need gene therapy, stem cells, CRISPR and emerging therapies to live that long. We need early translational intervention.
Jack died unexpectedly of respiratory failure in June 2015. These are pictures of him just 48 hours earlier at a golf outing.
I would have been willing to try CRISPR, down regulating PLP, gene therapy or stem cell treatments. Anything that could’ve produced gain in function, not just gain in myelin. I would’ve taken the most risk for something that could have improved his breathing, communication or muscle strength and control (like being able to hold his head up). I probably would not try anything that had greater than 20% chance of death or serious side effects. And, it would have been a tough decision to enroll Jack in any clinical trial earlier than Phase 3, especially if that disqualified him from potential future treatments. I’ve worked in pharma for 22 years and I look at treatments for rare, incurable disease a bit differently than medicines that control blood pressure, for example. I believe we need to increase the incentives for companies who are willing to invest in rare diseases like PMD, and grant them some leeway with trial designs due to the lower patient population and necessary risk associated with impacting the central nervous system.