KIF1A.ORG’s 23rd Research Roundtable meeting, “Structure to Patient Perspective: Vision Loss in KAND” was presented by KIF1A.ORG’s Dr. Dylan Verden. Let’s learn more about why KIF1A may impact vision, and where we can look for potential therapeutic leads.





Who Is Dr. Dylan Verden?

Dr. Verden is the Research Engagement Director for KIF1A.ORG. Before his current position, Dr. Verden received his PhD in Neuroscience studying differences in stroke response between juvenile and adult mice. He has brought his expertise in neurodevelopment and neurodegeneration to KIF1A.ORG’s science team.


Vision in KAND

Vision is one of our most integrated senses; in addition to helping us receive information and navigate our environment, vision plays a role in social interactions, learning, and even our sense of balance. This is why vision loss can have such a large impact on quality of life for KAND patients and their families.

Because so many KAND patients are nonverbal or have limited verbal skills, communicating about vision quality or vision loss can be difficult – it is challenging to know how well somebody else can see, and vision loss can easily be confused with a lack of interest or engagement.

Optic Nerve Atrophy

About half of KAND patients suffer from optic nerve atrophy. The optic nerve is a long bundle of 1.5 million axons that travel from your retina to the middle of your brain. Atrophy refers to a thinner-than-typical optic nerve, caused by a lack of, or loss of, neurons and their support cells.

The nervous system is resilient, and vision can persist even with substantially less neurons in the optic nerve; this means that some patients may have significant optic nerve atrophy as seen on an MRI, but still be able to see. Conversely other patients may have significant vision loss without obvious optic nerve atrophy, which could be related to disruptions of other visual circuits in the brain.

KIF1A in the optic nerve

KIF1A’s role in the optic nerve hasn’t been heavily studied, but multiple KIF1A cargo have been characterized in other models of vision loss, including glaucoma, a degenerative disorder of the optic nerve. Here are three examples of cargo carried by KIF1A in the optic nerve:

  • BDNF is a growth factor that plays crucial roles in neuronal development, and learning and memory. BDNF transport was reduced in a mouse model of glaucoma. Furthermore, both small molecule and gene therapy treatments that increase BDNF levels reduced neurodegeneration in these models.
  • BACE1 cuts proteins to their proper size, and a lack of BACE1 can cause a lack of insulation around optic nerve axons, disrupting electrical activity. Neurons lacking BACE1 are also more susceptible to stress, a vulnerability associated with neurodegeneration.
  • TrkA receptors impact neuronal development and survival. Loss of KIF1A has been shown to cause death of TrkA neurons that mediate pain. Treatments that act on NGF, a TrkA receptor signal, to the eyes of mouse models of glaucoma protected the optic nerve.

Treatments associated with these cargo are still under investigation and haven’t been applied to KIF1A models. But the ability to improve the nervous system without applying drugs through the skull or spine is a promising avenue of research.

Neurodevelopment vs Neurodegeneration

KAND diagnosis and treatment is complicated by the fact that it is both a neurodevelopmental and a neurodegenerative disorder:

  • Neurodevelopmental describes disorders where the nervous system doesn’t grow in the way that it should at typical milestones. For example, the neurons of the optic nerve might not be insulated to conduct electrical signals reliably, causing vison problems.
  • Neurodegenerative describes disorders where cells of the nervous system are damaged in a way that disrupts neural circuits. For example, unhealthy axons may die and leave debris that damages other nearby cells, causing periods when vision loss becomes worse.

In KAND, patients often experience neurodegeneration as their nervous system is developing, which contributes to different symptoms across our community.

This is why opthamology is a crucial component of the KOALA study – by collecting data from patients at different ages and different stages of KAND, we can better tease out the neurodevelopmental from neurodegenerative symptoms, and tailor our treatments accordingly.

In summary, KIF1A carries many cargo important for the health of the optic nerve. Because vision impacts so many aspects of our day-to-day life, learning to communicate about vision changes or loss with KAND patients is incredibly important

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