#ScienceSaturday posts share relevant and exciting scientific news with the KAND community. This project is a collaboration between KIF1A.ORG’s Research Engagement Team Leader Alejandro Doval, President Kathryn Atchley, Science Communication Associate Aileen Lam and Chief Science Officer Dr. Dominique Lessard. Send news suggestions to our team at impact@kif1a.org.

Recent KIF1A-Related Research

C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility

Cellular transport of cargo within the human body powered by KIF1A and other kinesin motor proteins is essential for proper neuronal function, as disruption to this process can lead to motor dysfunction and result in different forms of neurological conditions. Therefore, being able to understand what impedes cargo transport can bring insight to potential therapeutic strategies for neurological disorders, such as KAND and ALS, that result from impaired motor protein motility.  

In this article, researchers investigate a repeat sequence in the C9orf72 gene that is the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both are categorized as adult-onset neurodegenerative diseases that lead to the degeneration of neurons and the brain. Uniquely, ALS patients are seen with muscle weakness and FTD patients experience abnormalities with behavior and/or language. In this study, researchers show that this repeat sequence impedes microtubule-based transport mainly carried out by motor proteins. Additionally, they demonstrate that repeats containing the amino acid arginine called dipeptide repeats (DPRs), generated from the original repeat sequence, also result in cargo transport defects.

Their single molecule assays provided further evidence that these arginine-rich DPRs disrupt axonal transport machinery, such as dynein and kinesin-1 motor complexes, as they observed more instances of motors pausing on the microtubule tracks. Although these studies were conducted on the well characterized motor proteins, dynein and kinesin-1, there is potential for overlap with kinesin-3 motors like KIF1A, as both subfamilies are well known for their crucial roles in axonal transport. Increasing our understanding about what affects axonal transport machinery is helpful when thinking about strategies to prevent the progression of neurological disorders, such as ALS, FTD, and KAND. To learn more about this research, ALS, and FTD, check out the article and video below!

Rare Disease News

Data silos are undermining drug development and failing rare disease patients

In order to expedite rare disease therapeutic development as rapidly as possible, all invested stakeholders must commit to the “three C’s”: coordination, collaboration, and communication. One critical component of this process is making all relevant data open and accessible to invested parties. As this article discusses, the act of data siloing greatly impedes advancements and opportunities in the rare disease research and development ecosystem. What is a data (or information) silo? This is a situation in which only a limited number of individuals can access a set or source of data. As a result, this tends to cause a fragmentation of efforts to develop therapeutics for rare diseases and pushes an exorbitant burden onto rare disease patients and their families.

KIF1A.ORG is committed to preventing these obstacles from slowing down therapeutic development for KAND by implementing multiple initiatives, including our Tools for Development that are freely open to the scientific community and monthly Research Roundtable to facilitate regular and open communication in the KIF1A Research Network. To learn more about the impact of data siloing on rare disease drug development, check out the article below.

“We have an obligation to use and share patient data responsibly; coordination amongst all the researchers, foundations, and families for rare diseases can ensure more efficient and effective collection of this data to ultimately reduce the burden on families and accelerate the development of more effective treatments by promoting the best use of our most precious resources—patients’ time, limited energy, and goodwill.”

Diagnostic Yield of Whole Genome Sequencing After Nondiagnostic Exome Sequencing or Gene Panel in Developmental and Epileptic Encephalopathies

Among those diagnosed with rare neurological disorders, some patients experience developmental and epileptic encephalopathies (DEE), which refers to a group characterized by severe seizures and significant developmental delay. As DEE is associated with complex morbidity and high mortality, it is critical for these patients to receive a timely diagnosis in order to manage these harsh effects and seek potential therapeutics. In order to address this pressing need for efficient and accurate diagnoses for DEE, scientists are investigating different forms of genetic testing in hopes of determining one that will have the highest diagnostic yield and be a “one-stop shop” for patients.

In this study, researchers are comparing the benefits and limitations of whole genome sequencing (WGS) to other diagnostic platforms, such as exome sequencing (ES) and a multigene panel (MGP), to identify which has the best capabilities. From their collected data, they found that WGS was able to improve diagnostic yield compared to the other forms of testing, as it was able to identify more individuals with DEE. This conclusion provides researchers and clinicians with more insight on how to provide better diagnostic tools to patients with DEE and other rare diseases. Accessibility to genetic testing like WGS continues to be an obstacle that patients face, but being able to recognize the important role it plays in patient lives provides more incentive to make these forms of testing more available. To read more about this study and learn about DEE, click on the article and video below!

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