With genetic disorders, there is always a big question: do specific gene mutations respond differently to treatment? How can treatment be targeted to best suit the needs of patients? According to the Brown Daily Herald, researchers from Brown University’s Morrow Lab recently explored this line of questioning in relation to Christianson syndrome. During their research, the researchers attempted two lines of treatment. Altogether, they determined that certain cells may respond differently to treatment based on the underlying genetic mutations. See the full study findings in Science Translational Medicine.

The Research

Altogether, Christianson syndrome is a relatively new genetic disorder. Researchers are still working to understand the underlying mechanisms of the disease, as well as potential treatment options. To begin their study, researchers tested two separate treatment options for this condition. In both cases, researchers needed to first reprogram blood cells to become neurons.

But how did they do this? First, researchers sourced blood samples from five male patients with Christian syndrome. As a control group, the researchers used family members (brothers) who were not affected by this syndrome. After reprogramming the blood cells to become stem cells, researchers saved some – just in case something occurred in the experiment. Next, they turned the remaining cells into neurons, allowing the cells to retain the genetic information from whom they were sourced.

Then, researchers focused in on five forms of genetic mutations associated with Christianson syndrome. Of these, 80% were nonsense mutations and the remaining mutation was a missense mutation. Finally, researchers attempted both gene transfer and growth factor treatments. Through the research, they discovered:

• Both nonsense and missense mutations respond well to growth factor treatments.
• Overall, while nonsense mutations responded to gene transfer treatments, the missense mutation did not.
• Researchers believe that this is due to the amount of NHE6 already present. In nonsense mutations, patients do not have NHE6. Thus, adding a healthy gene allows for them to have healthy NHE6. In patients with missense mutations, there is NHE6 present but it is already mutated. Thus, adding additional healthy protein does not overcome the fact that the mutated NHE6 is already poorly functioning.

Ultimately, researchers believe that these new findings could help to develop future treatment options for patients with Christianson syndrome. However, they note that these targeted therapies should consider the underlying mutations to offer patients the best and most targeted lines of treatment.

Christianson Syndrome

According to the Christianson Syndrome Association (CSA):

Christianson syndrome is a genetic disorder that affects brain development. It is an “X – linked” disorder, [meaning it affects males].

SLC9A6 gene mutations cause Christianson syndrome. Normally, this gene encodes for NHE6, a type of sodium/hydrogen exchanger protein. NHE6 usually controls how many protons are found in the endosome, cells which help destroy or recycle certain molecules within our body. But in patients with Christianson syndrome, NHE6 does not work correctly and fails to carry out the necessary endosome processes. As a result, the endosomes are too acidic, causing some of the neurological symptoms associated with this condition.

Typically, symptoms of Christianson syndrome appear around ages 1-2. Initially, patients may experience recurrent seizures. Later symptoms include:

• Intellectual and developmental delays
• Ataxia (issues with movement, balance, and coordination)
• Microcephaly
• Absent speech
• Cerebellar atrophy
• Low muscle tone
• Gastrointestinal distress
• Strabismus or other eye movement problems
• Symptoms of Angelman syndrome and autism, such as a happy demeanor or unprovoked laughter
• Difficulty standing or walking