Currently, there are no known cures for CDKL5 deficiency disorder, a rare genetic disorder characterized by seizures and severe developmental delays. Treatment, rather, is symptomatic and supportive. However, a news release from the University of Pennsylvania Perelman School of Medicine suggests that new therapies – or even cures – may be on the horizon (even if a few years into the future). Researchers determined what role the CDKL5 gene played in following brain development. Eventually, the researchers determined that CDKL5 deficiency disorder is likely treatable into adulthood.
Interested in learning more? Take a look at the findings published in the Journal of Clinic Investigation.
CDKL5 Deficiency Disorder
CDKL5 gene mutations cause CDKL5 deficiency disorder, also known as CDKL5 or CDD. Normally, CDKL5 helps produce a protein that maintains normal brain function and development. The gene mutations typically appear where sperm and egg cells form, or during embryonic development. A deficiency of CDKL5 protein changes the way that the brain develops. An estimated 90% of patients with CDKL5 deficiency disorder are female. Males with this condition often have more severe developmental delays. Symptoms of this rare genetic disorder typically appear within 1 week to 3 months following birth. These include:
- Treatment-resistant seizures
- Intellectual disabilities
- Little or no speech
- Developmental delays, including delays in motor skills
- Feeding difficulties
- Repetitive hand movements, such as clapping or hand licking
- A high and broad forehead, deep-set eyes, widely spaced teeth, and a high roof of the mouth
- Microcephaly (abnormally small head size)
- Teeth grinding
- Scoliosis (abnormal curvature of the spine)
- Irregular breathing
- Sleep disruptions
- Feeding difficulties
- Constipation
- Gastroesophageal reflux
- Tapered fingers
Learn more about CDKL5.
The Research
In the past, researchers used mice models to evaluate whether the condition could be treatable. Nearly 9 years ago, these researchers developed mice models with a function-destroying mutation. Through this, they found that this type of mutation caused similar health and developmental problems in mice as they did in human patients.
Within this particular study, researchers wanted to understand the importance of CDKL5 during childhood brain development and even in adulthood. First, researchers discovered that CDKL5 was active in infancy, childhood, and adulthood within the mice models. However, switching off the gene caused the disorder to occur. Because of this, researchers found that this particular gene plays a role in adult brain health and function. Researchers then worked to re-active the gene. Doing so saw the animals return to fairly “normal” neurological function.
As a result, researchers hypothesize that CDKL5 deficiency disorder could be caused by a continued CDKL5 protein deficiency throughout life. Thus, it makes sense that this disorder could potentially be treated through some sort of gene editing therapy – even in adulthood.
Much more research is needed to understand whether treatment options are possible or could be developed. How could this gene therapy be created? Would it be able to directly affect the central nervous system? Since this experiment was mostly centered around male mice, how will experiments using female mice alter the results? This last question is especially pertinent considering that X chromosome inactivation in females is typically random or spontaneous. While additional research is necessary, it does suggest that, at some point in the future, there is hope for developing therapies for this patient group.
