#ScienceSaturday posts share exciting scientific developments and educational resources with the KAND community. Each week, Dr. Dylan Verden of KIF1A.ORG summarizes newly published KIF1A-related research and highlights progress in rare disease research and therapeutic development.
KIF1A-Related Research
The epithelial Na+ channel UNC-8 promotes an endocytic mechanism that recycles presynaptic components to new boutons in remodeling neurons
Glossary:
- Synapses: The region where two neurons communicate with chemical signals.
- Synaptic remodeling: Synapses can grow, shrink, or be removed, allowing our nervous system to adapt and learn.
- Endocytosis: From “endo” (in) and “cytosis” (of the cell), this describes when a cell reabsorbs part of its surface into itself. Endocytosis is one method of synaptic remodeling.
If a grocery store chain with multiple locations gets too many vegetables at one store, the simplest solution may be to send those vegetables to another store that needs more stock. This kind of re-use means less vegetables have to be produced, and less of them will be wasted – in other words, it saves energy and resources.
Some neurons have thousands of synaptic connections, and these synapses grow and shrink based on a neuron’s activity during development and learning. Much like the grocery store chain, these neurons want to use their energy and resources efficiently; if one synaptic site needs to shrink, its materials can be used in the growth of other synaptic sites. In this week’s article, researchers investigated how neurons in the C. elegans worm recycle materials between synapses.
The recycling of synaptic material is a complicated process with many moving parts, but a key player is UNC8, which helps to activate the disassembly of old synapses. Without it, not only do old synapses not get removed, but new synapses don’t grow properly. And UNC8 can only do its work if it’s transported from the cell body to old synapses. So what motor protein is responsible for UNC8 transport in these cells? You guessed it, KIF1A (or rather the worm’s version of KIF1A, UNC-104). Without KIF1A, UNC8 was stuck in the cell body.
The neurons studied in this research are called DD neurons, and they release GABA, a neurotransmitter that dampens neuronal activity. Prevalent KAND symptoms like epilepsy and spasticity are caused by excessive neuronal activity, so understanding how KIF1A mutations impact these dampening circuits could provide insight into KAND pathology.
Rare Roundup
US Representatives introduce legislation to support access to evidence-based care for rare disease patients
We’re already discussing reuse and recycling, so let’s consider the same theme in rare disease research. In our search for cures and treatment, we are using our best knowledge of KIF1A to find KAND-specific mechanisms. But in the meantime there is no approved treatment, so our families rely on symptom-specific treatments that have been validated for other diseases.
And that’s okay! KAND symptoms overlap with many disorders, and we can learn lessons from the efficacy of treatments in those diseases. But when those treatments aren’t covered by insurance, it serves as a barrier between rare disease patients and treatments that can improve their lives. This week, legislators proposed the Providing Realistic Opportunity To Equal and Comparable Treatment for Rare (PROTECT Rare) Act, which seeks to increase access to off-label treatments through Medicare, Medicaid, and private insurance.
As rare disease organizations continue to build a culture of collaboration to help our community as a whole, building a medical infrastructure that facilitates our shared goal is just as important.