#ScienceSaturday posts share exciting scientific developments and educational resources with the KAND community. Each week, Dr. Dominique Lessard and Dr. Dylan Verden of KIF1A.ORG summarize newly published KIF1A-related research and highlight progress in rare disease research and therapeutic development.

KIF1A Research: From the Archives

Patterns of Expression of Bardet-Biedl Syndrome Proteins in the Mammalian Cochlea Suggest Noncentrosomal Functions

One recurring question in our community is why KAND impacts some functions, but not others. For example, why is vision loss common while hearing loss is rare?

These questions can be hard to answer because we’re still learning about where and when KIF1A expression is important in the body. The unique developmental timelines and needs of different circuits mean that a given protein may play different roles in different systems. This week’s article, focused on a different disease called Bardet-Biedl syndrome, also characterized KIF1A expression in cells that underlie our sense of hearing.

The authors were studying hair cells, which have long tips (like hair) that flex in response to vibrations caused by sounds, and send signals to neurons. They found that before early development in mice, KIF1A is expressed in the tips of hair cells. At the age of hearing onset, KIF1A expression drops off in the tips but remains at high levels in the base of hair cells, potentially reflecting a changing role of KIF1A during development. The authors did not investigate KIF1A expression at older ages.

This raises an important point: KIF1A is often called a neuron-specific kinesin. Hair cells do transmit neurotransmitters, but their morphology is different from neurons. It might be more accurate to say KIF1A is a neuron-enriched kinesin — keeping an eye out for other cells’ expression of KIF1A could help us learn more about symptoms.

So why don’t we see more hearing loss in KAND? We’re not sure. It may be that other kinesins can compensate for mutant KIF1A during development, or that KIF1A expression is less important in maintaining hair cell function throughout life.

While it is more important to our KAND community to learn about KIF1A in senses that do have deficits, understanding why some sensory circuits function well with mutant KIF1A can give us important insights into KIF1A biology.

Want to learn more about hair cells and hearing? Check out the video from the NIH below!

Rare Roundup

Study highlights the multibillion dollar burden of rare disease

Health has widespread effects on so many elements of our lives, which is why the cost of a disease goes beyond what is charged for a hospital visit. These indirect costs include lost productivity and caregiver investment and are often underestimated, especially for rare diseases that aren’t codified in our medical insurance systems. An accurate idea of this financial burden is necessary to establish more adequate care systems.

This is why the EveryLife Foundation created a survey of 1,400 rare disease patients, comparing their 2019 expenses to documented direct healthcare costs. They quantified something that most families with rare diseases already understand — over half of expenses were indirect and covered by the family. The EveryLife Foundation is using this information to advocate for follow-up studies and recommend policy to lawmakers, including more comprehensive documentation of rare disease patients and the costs they assume.

Acadia Pharmaceuticals Submits New Drug Application to the U.S. FDA for Trofinetide for the Treatment of Rett Syndrome

Complex neurodegenerative disorders like KAND are urgently needed and can also be difficult to develop, which is why success stories are so important. This week Acadia Pharmaceuticals announced that it has submitted trofinetide in a New Drug Application to treat Rett Syndrome.

Rett Syndrome is a developmental neurodegenerative disorder that impacts movement, communication, and sleep among other symptoms. Trofinetide is a synthetic analog of insulin-like growth factor (IGF-1), a hormone that promotes cellular growth metabolism and survival against stress in neurons and the glial cells that support them. Trofinetide has shown promising effects in a phase 3 clinical study of children and adolescents with Rett Syndrome, and Acadia hopes trofinetide will be approved for children two years or older with the disease. There’s more to learn about IGF-1 mechanisms as they related to neurodegeneration in KAND, which is why our drug screening projects are so important: We’ll be keeping a close eye on drugs like Trofinetide as we move forward!

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