#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-Related Research

Active zone protein SYD-2/Liprin-α acts downstream of LRK-1/LRRK2 to regulate polarized trafficking of synaptic vesicle precursors through clathrin adaptor protein complexes

When a warehouse ships products to the homes that order them, precision matters – products on the same delivery pallet eventually need to be sorted into the right trucks so they get to their correct destination.

This is true for cargo in neurons, too – many types of cargo are made and packaged in the cell body, and they need to be identified and sorted to motor proteins that can carry them to the intended  part of the neuron.

In this week’s pre-print*, researchers at the Tata Institute of Fundamental Research in Mumbai, India used the C. elegans worm model to investigate how neurons sort these cargo for transport by unc-104, their analogue of KIF1A.

The cargo in question includes synaptic vesicle precursors (SVPs), which are building blocks for connections between neurons, and lysosomal proteins, which help degrade proteins and cellular debris. Early on, these cargo are put on the same delivery pallet, called synaptic vesicle lysosomes. Separating and transporting these cargo is an important aspect of neuronal function.

To understand how this cargo sorting happens, the authors mutated (or altered) several genes involved in the process and asked if  KIF1A transport would change.

They found that when these cellular “sorters,” LRRK2 and AP-3, were mutated or absent, shared SVP-lysosome pallets weren’t properly separated. This caused another protein called liprin-α, which binds to KIF1A and helps its attachment to SVP cargo, to transport these combined pallets, resulting in cargo mislocalization.This goes to show how KIF1A relies on sorting proteins to make sure that it’s carrying the right cargo.

Studies like this give us a fuller picture of how KIF1A interacts with specific types of cargo, which can help us better understand the relationship between KIF1A and neuronal dysfunction in KAND.

*What’s a pre-print? Check out this #ScienceSaturday post to learn more

Rare Roundup

US FDA to take steps to help gene therapies get accelerated approval

In the fight to find new therapies for genetic disorders, half the battle is developing technologies and approaches that can cure a genetic mutation; the other half is getting these treatments approved.

As a relatively new treatment approach that combines several factors of drug administration, gene-targeting, and gene-fixing, there are many factors that play into certainty of the safety and efficacy of a new gene therapy.

But genetic disorders often represent a known and urgent risk, and we require a more streamlined process that allows us to get treatments to patients faster.

In acknowledgment of this need, the United States Food and Drug Administration has announced its approval of the use of biomarkers in the assessment of gene therapies. Biomarkers are a broad set of indicators of patient health that can be measured, including blood pressure, heart rate, and body fat; digital devices like smart watches have made measurement of many of these biomarkers easier than ever, and the encouragement to broaden the use of biomarkers in gene therapy approval may loosen a major bottleneck that slows the assessment of these therapies.

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