Landon’s Story

Meet Our Son, Landon

Landon was born on January 4th, 2017 in St. Louis, Missouri.  Prior to birth, ultrasound imaging revealed brain abnormalities which were confirmed with an intrauterine MRI.  The day after Landon was born, a second MRI was performed of his brain and noted rare brain structure malformations including lissencephaly (“smooth brain”), agenesis of the corpus callosum (missing the midline structure of the brain), and a small cerebellum.  At about 4 months of age, Landon began to demonstrate atypical movements.  Initially his pediatrician contributed his behaviors to episodic acid reflux.  These movements began happening more often and his neurologist subsequently ordered an EEG that confirmed these movements were happening due to seizure activity.  Despite a trial run of a common anti-seizure medication known as Keppra, the seizures seemed to be getting worse and were prolongated.  Landon was then hospitalized at Children’s Hospital in St. Louis, MO in late June 2017 and diagnosed with an even more rare seizure disorder known as infantile spasms.  He was prescribed a month long treatment of a steroid called prednisolone.  Following that treatment, he was transitioned to an anti-epileptic medication called Sabril (Vigabatrin).  This medication alone did not keep the seizures away so a second medication was added called Onfi (clobazam).  He was on both medications for approximately 14 months.  We were eventually able to wean Sabril over the course of a year and dual therapy eventually ended in October 2018.  Now, his epileptic seizures are now controlled with Onfi/clobazam alone.

Additional challenges for Landon include global developmental delay, a mix of hypotonia (low muscle tone of his core and neck) and hypertonia (rigid and guarded upper and lower extremities), cortical vision impairment, and feeding difficulties.  He is making great strides due to the countless hours of home as well as outpatient physical, occupational, vision, and speech therapy.

On February 8th, 2018, during a car ride home from therapy, Landon’s geneticist confirmed/identified a single “candidate” gene mutation that may be the cause of all of Landon’s medical issues.  That gene is known as “CAMSAP1”.  Subsequently, the genetics office conveyed “there had not been any research regarding that gene” and that “there really isn’t anything that could be done and they’d revisit it in two years”.  The mutated gene Landon inherited was autosomal recessive meaning as carriers his parents had a 25% chance of passing the gene to other future offspring.

HOWEVER…

Landon’s father Joe, a medical practitioner in his own-right, would not take this information as gospel.  For the next 3 months he would spend countless hours researching and piecing together seemingly unrelated research about CAMSAP1 and proteins that it interacted with.  On May 2, 2018, it seemed to have all come together!  A study was published by Dr. Jana Marcette et. al., identifying a gene rescue study that was completed at Washington University in St. Louis, MO whereby a small nematode demonstrated Landon-like movements until the gene was corrected and it SWAM AWAY!  Joe contacted Dr. Marcette who was astonished that her post-doctoral research may have such profound implications on potentially curing a child in her own community.

On May 23, 2018, Dr. Marcette, Randy Ray (future MD), and Joe secured a meeting with Dr. David Curiel, also at Washington University in St. Louis, and presented the findings of the research to him.  Dr. Curiel was amazed at the research, and the BEST scenario happened as he agreed to advance the research of CAMSAP1 in hopes of finding a safe gene therapy/cure for Landon in his lab!  The plan involved furthering the research of this gene by creating a mouse knockout model with a CAMSAP1 mutation.

Dr. Curiel reached out to The Jackson Laboratory, a company that creates rodent models demonstrating rare conditions.  After a few months of careful planning, four “founder mice” were born ironically on November 3rd, 2018 (Landon’s parents’ wedding anniversary).  These mice are essentially carriers of the gene mutation but were not effected as they had one normal copy of the gene.

In December 2018, these four founder mice were bred with normal mice.  Provided that the laws of genetics would hold true, 50% of the offspring would then be true CAMSAP1 mutants.  Further irony ensued, and in January 2019, the second generation mice were born with 1/2 of the litters being born on Landon’s original due date.

In May 2019, it was discovered that this attempt lead to results that were somewhat disappointing as there would not be any mice born in any of the litters with two abnormal copies of the gene.  Despite this brief setback, we did learn from our initial efforts that there is a certain aspect of the CAMSAP1 gene that is necessary for any organism to survive birth.  Luckily, research had been published by Dr. Takeichi from Japan that indicated that the two other CAMSAP genes, CAMSAP2 and CAMSAP3, did have successful knockout mouse models.

Joe was tasked to discover where the genes were modified for the two other CAMSAP knockout models.  Amazingly, after only five hours of sending an email to the Dr. Takeichi, a reply was received with the answers to the question.  Furthermore, much to the surprise of all involved, Dr. Takeichi conveyed that his colleague in China, Dr. Meng, was actively researching a CAMSAP1 mouse model that was indeed successfully created!  As Dr. Meng continues his research, Joe reached out to another lab at Washington University School of Medicine in St. Louis, MO whose interest are of neuronal genetics, cell-to-cell communication, intracellular structures and genes associated with axon outgrowth – exactly what CAMSAP1 has been implicated to play a major role in!

After contacting the new lab, it was decided and agreed upon to create induced pluripotent stem cells (iPS cells or iPSCs) from Landon’s own blood cells.  This process would be accomplished by adding four genes (“Yamanaka Factors”) to his blood cells to reengineer them back to their pluripotent stem cell state.  In doing so, the lab will be able to engineer or differentiate these new iPSCs into whatever tissue type that would be needed or desired (ie nerve cells, muscle cells, skin cells, etc.).  Once the newly created differentiated cells are created, they would then be analyzed to see how much CAMSAP1 mRNA exists with each cell type, respectively, and the data would be compared to a normal cell with a normal CAMSAP1 fully functional gene.  This process was anticipated to take approximately 6-8 weeks and be completed by end of October 2019.

Much to the surprise of the researchers at Washington University working on iPSC induction, they were not initially able to perform the transformation on Landon’s cells despite several attempts.  To work around this, the researchers asked that we provide them with additional samples of blood from Landon as well as Lauren and myself.  The plan is to analyze and compare our “normal” samples with that of Landon’s.  Surprisingly, the lab successfully created iPSCs from the second blood sample, and they are currently in the process of analyzing them and collecting the data. These iPSC cells, void of the CAMSAP1 gene, will be converted to various tissue types and compared to normal cells to see the effects of the absence of the CAMSAP1 gene respective to each type.

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