KIF1A.ORG In the News!
Want to learn more about KIF1A.ORG’s history, strategy and mission? Earlier this week KIF1A.ORG co-founder Luke Rosen spoke with Sandra Shpilberg of Adnexi to discuss the importance of meaningful collaborations in the rare disease space as we march towards a cure for KIF1A Associated Neurological Disorder. Enjoy this candid interview: “When the Clock is Ticking: Ideal Collaborations to Develop Treatments & Cures.”
Recent KIF1A-Related Research
New Research Simplified Resource From KIF1A.ORG
KIF1A.ORG recently published a NEW Research Simplified article created by Dr. Jayne Aiken from the Holzbaur Lab at the University of Pennsylvania. In this resource, Dr. Aiken walks us through the history of KIF1A, starting with the discovery of kinesins and ending on our current understanding of KAND-related KIF1A mutations. Thank you Dr. Aiken for being a part of our Research Network as well as educating and engaging families in the history of KIF1A discovery!
Going Too Far Is the Same as Falling Short: Kinesin-3 Family Members in Hereditary Spastic Paraplegia
To highlight even more amazing contributions from members of our Research Network, this week we are featuring a review article written by the Silverman and Niwa labs. This review is focused on understanding known kinesin-mediated transport deficiencies in various forms of hereditary spastic paraplegia. Not only does this review go in depth about KIF1A structure, function and cargo trafficked by KIF1A but it also discusses the roles of KIF1C and briefly KIF5A. The authors go on to detail the relationship between KIF1A/KIF1C mutations, discussing the difference between loss of function vs. gain of function mutations and how this level of variant knowledge informs our understanding of HSP and related disorders. Lastly, the authors discuss therapeutic challenges and ideas for curing KIF1A/KIF1C related HSP and other related disorders by advancing our understanding of the disease mechanism, going beyond the current approach of treating the surface-level symptoms.
Why have we been spending so much time talking about kinesin motors other than KIF1A? Due to the fact that KIF1A does not operate in a vacuum! The inside of a cell is a highly complex, crowded and intricate environment. In order for our cells to operate efficiently, all of the components inside of the engage in a tightly choreographed cellular dance. Every cellular component has its part, dance moves, and timing and the cellular dance is only successful when all of the components work together. This is especially pertinent when we think about kinesin-based cargo transport as it is currently thought that some kinesin motors may need to work together in teams to “share the load” while transporting certain cargo. While we always want to focus on the role KIF1A is playing in a cell, it is important to broaden our focus to other kinesin players as well as they may teach us a lot about KIF1A!
Rare Disease News
Watch out, CRISPR. The RNA editing race is on.
What would the field of gene editing be without acronyms? Well today we have a new one for you… ADAR! Standing for “adenosine deaminase acting on RNA,” ADAR is a type of cellular machinery responsible for introducing single-letter changes in the RNA code. While this machinery already exists in our cells, many researchers are trying to turn ADAR into a therapeutic RNA editing machine.
How is this RNA editing technique different than the DNA-level CRISPR editing we hear about so often? First, unlike DNA editing, the effects of RNA editing are reversible. This is because the “copy machine-esque” components inside of our cells produce copies of RNA that are constantly being degraded and replenished. This makes the effects of this RNA editing technique “reversible” and very similar to antisense oligonucleotide (ASO) therapies. Second, this technique does not introduce any foreign protein in the body. Instead, it relies on commandeering pre-existing machinery (ADAR) within the cell. While not a new technique, this type of RNA editing is undergoing a revival of investigation. Take a look at this article to learn more about the history and current state of this gene editing technique! Additionally, if you’d like a refresher on the differences between DNA and RNA, enjoy the video below.
New genetic analysis method could advance personal genomics
Diagnosis of genetic rare diseases is often an arduous hurdle faced by members of the rare disease community; it can take patients and families years, sometimes decades, to receive a proper diagnosis! These delays in diagnosis can have serious implications on patient health, especially if a patient is experiencing a substandard quality of care. How can we begin to tackle a problem as large as this? The Battle lab at Johns Hopkins University has a suggestion. As a part of the larger Genotype-Tissue Expression (GTEx) Program, the Battle lab has developed a computational system that can analyze preexisting genetic and gene expression data to identify potentially problematic and rare variants in one’s genetic code. Upon successful validation, this technique would greatly advance the field of personal genomics. Check out the article below to learn more!
“The implications of this could be quite large. Everyone has around 50,000 variants that are rare in the population and we have absolutely no idea what most of them are doing,” Battle said. “If you collect gene expression data, which shows which proteins are being produced in a patient’s cells at what levels, we’re going to be able to identify what’s going on at a much higher rate.”