#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.
Identifying mRNAs Residing in Myelinating Oligodendrocyte Processes as a Basis for Understanding Internode Autonomy
Did you know that every cell in your body has the KIF1A gene? Considering this, why do mutations mostly cause symptoms in nervous system cells?
The answer is that only certain cells actually make and use KIF1A enough for a mutation to cause problems. Cells that need KIF1A make messenger RNA (a blueprint of building blocks that comprise KIF1A) from the gene, and make protein from that messenger RNA.
The KIF1A motor protein is enriched in neurons – it’s produced and used by many types of neurons, especially those with long projections that rely on KIF1A’s speed over large distances.
But neurons aren’t the only cells in the nervous system, or the only cells that rely on precise cargo trafficking. In this week’s #ScienceSaturday, researchers investigated KIF1A expression in another cell type in the brain.
That cell type is the oligodendrocyte (literally, “cell with a few branches”). Each oligodendrocyte wraps several axons in a sheath of myelin, a membrane that insulates the axon so electricity from the cell body doesn’t leak out before reaching its destination. The areas of axons that are wrapped in myelin are called internodes.
Myelin is fatty and white, so myelin-rich areas of the brain are called white matter. White matter tracts are the high-speed highways of your brain, and white matter atrophy is a symptom observed in many KAND cases.
Making myelin isn’t easy – a single oligodendrocyte can make hundreds of times its size in myelin!
The oligodendrocyte also has to coordinate with several neurons to decide where the myelin should make internodes. Getting the right cargo to the right myelin sheath is crucial, but we’re still learning how oligodendrocytes accomplish this.
The authors used a process called fractionation to blend up cells and isolate the fatty myelin from other cell compartments, allowing them to look at RNA expression in myelin. They found that an appreciable amount of KIF1A RNA was found in myelin, indicating a potential link between KIF1A and oligodendrocytes.
There are some caveats: Because myelin is wrapped tightly around axons, some of the KIF1A RNA may be coming from axons that got caught in the myelin fraction. A next step would be to look at KIF1A expression in intact oligodendrocytes and myelin. Follow-up studies are important so we can learn how KIF1A is used by non-neuronal cells in the brain, and whether this contributes to white matter symptoms in KAND.
From Lab to Living Room: mRNA Therapeutics
When we talk about KIF1A.ORG’s “multiple shots on goal,” we’re referring to the idea that each therapeutic has its own benefits and drawbacks – there is unlikely to be a one-size fits all treatment for KAND, so it’s important to explore these options in parallel. Small molecule drugs, assistive technology, gene therapy, and RNA-based therapies are all “shots on goal,” but these are all huge and dense subjects to digest.
In the last year we’ve discussed RNA-based therapies quite a bit in the context of Antisense Oligonucleotides (ASOs) with our partners at Ovid. Today we’re highlighting an article and video that give an intuitive explanation of how RNA, and RNA-based therapies, work in your cells.