#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

Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations

Roughly 1% of the general population experience intellectual disability (ID) and autism spectrum disorder (ASD), both of which are neurodevelopmental disorders that can affect children at a young age. A big challenge that many clinicians face with these disorders is determining the etiology, or root cause, of ID and ASD because they can result from a variety of factors. However, now with exome sequencing, individuals with gene variants tied to these disorders can be quickly identified, which helps patients arrive at an earlier diagnosis and receive appropriate care.  

Patients receiving accurate diagnoses is very crucial in gaining a deeper understanding of disease pathogenesis, or the process in which diseases develop. This information is also important in creating treatments that are tailored towards specific diseases such as ID and ASD. Therefore, this study was conducted to determine if exome sequencing can drastically improve the rate of diagnosis for individuals suspected of ID and/or ASD. In this paper, researchers explain that in a cohort of 200 patients who underwent exome sequencing, 41 disease causing variants were identified with a detection rate of 22%. In addition, 45 variants of uncertain significance were determined and new candidate genes for ID and ASD were also revealed.

As ID is a clinical symptom that is observed in KAND patients, multiple KIF1A variants were also detected by the exome sequencing run to cause this form of neurodevelopmental disorder. Overall, this study emphasizes the value and effectiveness of exome sequencing in being a first-choice diagnostic tool for patients suspected with ID, ASD, KAND, or other neurodevelopmental disorders. In performing exome sequencing, researchers can more efficiently narrow down the etiology of disease pathogenesis for disorders like ID, ASD, and KAND. To read more about this exome sequencing study, check out the article below!

Spatial regulation of microtubule-dependent transport by septin GTPases

We as humans have a vast amount of functions that are highly regulated by the many moving parts in our bodies. One process that is absolutely crucial for our proper brain development is the transport of important cargo and biological structures within our cells. With intracellular transport being essential for human survival, there are many players involved that help facilitate the coordination of these complex pathways. A particularly important class of proteins that helps control the localization and interactions of other proteins on microtubules is known as septins. Septins play a major role in regulating the movement of motor proteins, such as kinesin and dynein, and guiding transport of cargo carried by these motors. 

In this review, the authors highlight the significant roles that septin plays in microtubule-dependent transport and propose that septin also provides a “traffic code” to direct specific movement of cargo on microtubules. Additionally, these researchers also discuss the involvement of septins in major processes such as mitosis, or cell division, and how it guides molecular motors to their designated locations to carry out their functions. With KIF1A being one of many kinesin motors, this review also highlights the effects that septins have on KIF1A. The authors point out that a particular septin protein called SEPT9 promotes KIF1A motility and ultimately the transport of KIF1A motor cargo. By understanding the many proteins that regulate and affect KIF1A function, a more comprehensive picture is gained of KIF1A and its involvement in the complex pathways of microtubule-dependent transport. Ultimately, this knowledge will allow for more insights into the disease form of KIF1A, as researchers now know of other processes and interacting partners that can lead to KIF1A defects. For more in depth details of this review highlighting the roles of septins on motor proteins, check out the article below!

Rare Disease News

David Liu takes the wraps off $315M launch round for Prime Medicine and new CRISPR tech that gave Bob Nelsen a ‘holy crap’ moment

The field of gene editing is on the brink of revolutionary advancements as Dr. David Liu recently published his lab’s work on a new gene editing technology called prime editing or CRISPR 3.0. As a quick reminder, CRISPR is a type of gene editing that was adapted from the natural defense mechanisms of bacteria to be used to alter DNA sequences in plants, animals, and humans as a potential method to treat diseases. Now improving this technology, Dr. Liu and his team announced the start of a new company called Prime Medicine that will be licensed to use this upgraded form of gene editing to overcome barriers that older forms of CRISPR could not. 

Prior to prime editing, CRISPR technology could only find the gene of interest and break the DNA sequence. Although powerful at the time, it was still limited in the diseases that it could target through this one method. Additionally, this gene editing was advanced and was able to repair individual DNA bases, but only up to 4 out of 12 possible ways. Now with prime editing, all 12 possible ways bases can be changed are now repairable, along with the ability to have long stretches of DNA be inserted, replaced, or deleted! The next goal that Prime Medicine has in mind is to apply this gene editing technology across the body in all forms of tissues and to identify methods of delivery that will be effective in carrying out these processes. With this capability, this new CRISPR technology has many prospects for treating and targeting multiple diseases, especially rare ones. To read more about this incredible CRISPR advancement, check out the article below!     

Gene therapy success offers hope for reversing rare genetic diseases

The field of gene therapy has been experiencing a lot of breakthroughs recently and it has been so exciting to read about these new discoveries! One of the most interesting to learn about is a current landmark study that revealed a novel method for delivering gene therapies to specific locations in the brain that could halt the damage caused by developmental diseases. This research was targeted at children born with a rare disease called AADC deficiency. AADC is an enzyme that is essential for the synthesis of dopamine and serotonin; thus, this disorder is a result of a mutation in a gene that is responsible for the creation of these important neurotransmitters. As a reminder, neurotransmitters are signal molecules that are crucial in helping neurons communicate, and dopamine and serotonin play an important role in brain regulation and development. Therefore, children with AADC deficiency experience developmental deficits and motor disability, which results in their inability to speak and to carry out basic functions independently. 

In this study, seven children between the ages of four and nine were enrolled in a Phase 1 trial. The scientists then used a new surgical technique that involved real-time magnetic resonance imaging to deliver the gene therapy to specific regions in the brain. As a result of this new therapy, six children from the study no longer experienced seizures that were characteristic of the disease and slowly some were starting to speak and walk! From this, researchers were fascinated to learn that developmental damage could be altered from gene therapies and that in itself is instilling a lot of hope and promise for the future treatments of rare degenerative diseases. Want to read more about this study? Check out the article below!

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