Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
Prenatal delivery of a therapeutic antisense oligonucleotide achieves broad biodistribution in the brain and ameliorates Angelman syndrome phenotype in mice
We previously published about this research in a story titled “Could We Treat Angelman Syndrome and Other Genetic Disorders in Utero?” which can be found here. The study was originally published in the research journal Molecular Therapy. You can read the full text of the study here.
This research was affiliated with UC San Francisco.
What Happened?
Though it doesn’t happen often, sometimes physicians are able to diagnose genetic disorders in a child before the child is born. As more diagnoses are made pre-birth, scientists have been researching methods to allow for treatment to begin before birth as well. One method has involved delivering treatment to the fetal brain through cerebrospinal fluid. In this study, the scientists pioneered a less invasive method that appears to be just as effective.
The advantage to treating genetic disorders like Angelman syndrome in-utero is that it could potentially prevent the development of the earliest symptoms from developing. Additionally, in the most severe manifestations of a genetic disorder, a patient may have already suffered irreversible damage that can’t be rectified following birth. The brain of a fetus is also more amenable to treatment because the blood-brain barrier hasn’t fully developed.
The study involved the use of a mouse model of Angelman syndrome, a genetic disorder. Prior studies have found that the expression of the part of the gene that contributes to the disorder can be altered prior to birth. The approach utilized a class of therapies called antisense oligonucleotides (ASOs) which engage with RNA (which is responsible for the creation of proteins) in order to change the expression of genes.
The therapy was injected directly into the amniotic fluid instead of the cerebrospinal fluid, resulting in improvements in learning and motor function in the young mice after they were born. Administration through the amniotic fluid allowed the treatment to saturate many of the vital organs. In addition, a much higher dose level could be safely used, resulting in a more ‘slow release’ approach. Overall, the research team concluded that administering treatment to the amniotic fluid was a less invasive method that didn’t suffer any declines in effectiveness.
Why Does it Matter?
There are a lot of genetic disorders out there—thousands in fact, and the majority of them don’t have an approved treatment. More are being discovered every day, and they can be difficult to treat and diagnose. The findings from this study offer a more effective, less invasive option that could help prevent the onset of the worst symptoms in cases where the disorder can be diagnosed in-utero. While Angelman syndrome was the disease that was treated in the study, the findings have implications for a wide variety of genetic conditions that can be diagnosed before birth:
“Both types of prenatal injections we tried, into the cerebrospinal fluid and into the amniotic fluid, allowed the therapy to penetrate deep regions of the brain that are critical areas to treat for Angelman syndrome. This is a big hurdle to overcome when treating genetic conditions of the nervous system.” – Maria Clark, BS, Research Associate, UCSF
Future research will include attempting to replicate the findings in a large animal model and determine if treatment administered in the amniotic fluid can cross into the spine and brain in the same way.
About Angelman Syndrome
Angelman syndrome is a type of genetic disorder that impacts the nervous system. This disorder is not inherited from parents, but instead occurs as a spontaneous genetic alteration, typically the deletion of a segment from chromosome 15 called UBE3A. A mutation of this gene can also cause Angelman syndrome. Symptoms of this disorder can include seizures, developmental delays, a small head, an excited and happy demeanor, trouble with balance and movement, intellectual disability, and speech issues. Patients may share certain facial characteristics. Symptoms become noticeable at about one year old. Treatment is supportive and symptomatic, and there is currently no cure. Patients have a strong desire for social interaction, and despite limited language are able to understand much of what is happening around them. Life expectancy is generally close to that of an unaffected person. To learn more about Angelman syndrome, click here.
