Study of the Week: Researchers Discover Cause of Norrie Disease Hearing Loss

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…

Norrie disease protein is essential for cochlear hair cell maturation

We previously published about this research in a story titled “NDP Deficiency Causes Deafness in Norrie Disease” which can be found here. The study was originally published in the scientific research journal Proceedings of the National Academy of Sciences of the United States of America. You can view the abstract of the study here.

What Happened?

Norrie disease is a rare disease that is known to cause blindness and deafness. The disease is caused by mutations affecting the NDP gene. However, while the gene that causes the symptoms to emerge has been known in the past, researchers were less certain about the mechanism behind it. In this study, scientists set out to solve this mystery and found that deficiency of a protein called Norrie disease protein (NDP) leads to the hearing loss that many patients experience.

Researchers had previously theorized that vascular changes triggered by Norrie disease were the reason behind hearing and vision loss. Deficient NDP causes hearing loss because the protein is critical for the survival and maintenance of hair cells. These cells are found in the cochlea and are absolutely essential for hearing. Using a mouse model, the scientists found that the hair cells atrophied and died without NDP. Others had a faulty expression of proteins, preventing them from functioning normally.

The scientists also determined using a mouse model of Norrie disease that the Wnt pathway, which is supposed to play a role in the regeneration of hair cells, could potentially serve to mimic the effects of NDP. In the mouse model, this pathway was able to prevent hearing loss. The scientists also identified another method which involved overexpressing NDP in neighboring cells that could do the same.

About Norrie Disease 

Norrie disease is a rare genetic disorder that is most characterized by blindness in patients at birth. Most patients also experience a progressive decline in hearing starting in the childhood or teen years. This disease is caused by mutations affecting the NDP gene. Since the gene is located on the X chromosome, and Norrie disease is inherited in an X-linked recessive pattern, almost all patients are male. Symptoms include leukocoria (pupils that appear white when light is shone on them), cataracts, psychotic features, ataxia, behavioral abnormalities, atrophy of the iris, developmental delays, and progressive hearing loss eventually leading to deafness. There is no cure for Norrie disease and treatments are limited; in some cases, laser therapy or surgery can be beneficial. Cochlear implants or hearing aids can be effective, and supportive therapy and monitoring are needed to address behavioral challenges. Emotional support is also important as patients often suffer from isolation after losing both their sight and hearing. To learn more about Norrie disease, click here.

Why Does it Matter?

These new discoveries have major implications for the future development of disease-altering therapies for Norrie disease. Currently, many patients are left with limited options and are forced to adapt to vision and hearing loss along with other debilitating symptoms. The development of a treatment that could intervene in preventing hearing loss would be a game-changer for these patients.

The fact that the research also unearthed two potential mechanisms for a treatment that could halt hearing loss makes the results of this research many times more significant. These findings could have implications for other forms of hearing loss as well:

“There are a number of implications of this work, one that clearly NDP is a part of the overall picture of Wnt signaling in the normal ear…while that work is very early and experimental, this new study strengthens our hypothesis that Wnt signaling is important for regenerating hair cells.” – Albert Edge, Ph.D., research lead

Since hearing loss in Norrie disease doesn’t occur until several years into the patient’s life, those that receive a timely diagnosis could begin receiving treatment for hearing loss before it begins, thereby preventing its occurrence entirely. The scientists have already made plans to further evaluate the two treatment approaches that they found in future studies.

“Through our research, we’ve identified potential pathways for future treatments to prevent the hearing loss. These findings may also have implications for more common forms of permanent hearing loss.”

With the results from this study, the Norrie disease patient community has a new cause for hope for the future.

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