#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 email@example.com.
Recent KIF1A-Related Research
Kinesin-binding protein remodels the kinesin motor to prevent microtubule-binding
As kinesins play important roles in transporting cargo within cells, there are many aspects in which these motor proteins are regulated in order to function properly. One way in which kinesins are regulated is through kinesin-binding protein (KIFBP), which was recently discovered to inhibit binding to microtubules. Along with this finding, researchers also noted that mutations in KIFBP were associated with a neurological disorder called Goldberg-Shprintzen syndrome (GOSHS). To further understand the role of KIFBP and the pathways in which it inhibits kinesin from binding to microtubules, researchers set out to elucidate KIFBP’s structural mechanism in hopes of uncovering these unknowns.
In this paper, researchers detail how they were able to determine the structures of KIFBP alone and bound to kinesins. Further analysis of this data revealed the regions of KIFBP that are involved in complex formation, which gives researchers insight into the underlying mechanism of its inhibitory activity. They found that KIFBP undergoes a 2-pronged mechanism to carry out its function. First, KIFBP blocks kinesin interaction with microtubules at the microtubule surface. Then KIFBP changes the shape of the part of kinesin that is responsible for microtubule binding, which further prevents kinesin-microtubule interaction. From this paper, these researchers propose a mechanism of KIFBP-facilitated kinesin inhibition, which can be useful in understanding the human diseases associated with the pathway’s dysfunction. As KIF1A is among the motor proteins that KIFBP interacts with and inhibits, gaining more knowledge on how KIFBP acts on KIF1A can be beneficial in learning more about disease forms. To read more about this paper and KIFBP, check out the preprint paper below! Want to learn more about one of the experimental techniques used in this study known as Cryo-Electron Microscopy? Have a look at the below video as well!
Rare Disease News
The parents hoped an existing drug might keep their kids from having seizures. Then they saw the price.
While rare diseases may have differences in clinical presentation or root cause, all of us in the rare disease community are united by a common goal: to identify therapeutic options aiming to help treat and cure individuals living with rare diseases. Impressively, SLC6A1 Connect’s founder Amber Freed has done just that by identifying a drug that could help treat an aggressive form of epilepsy resulting from mutations in the SLC6A1 gene. This drug, known as Ravicti, has already been approved by the US FDA, which makes this drug an enticing candidate for a SLC6A1 drug repurposing effort. However, alongside this potential therapeutic milestone comes a difficult obstacle to overcome: Ravicti is one of the most expensive drugs in the world, costing around $740,000 per year. To tackle this jaw dropping price tag, Freed has continued to push for novel avenues of drug access for SLC6A1 patients, including teaming up with the SRXBP1 Foundation to initiate a Ravicti clinical trial. To read more about the story behind SLC6A1 Connect and the STXBP1 Foundation’s mission for equitable drug access, click on the article below! Want to learn even more? Have a look at the videos below to learn more about SLC6A1 and STXBP1 as well as how you can support these communities.
Envisioning an actionable research agenda to facilitate repurposing of off-patent drugs
The idea of drug repurposing, or the use of an already existing drug for new therapeutic avenues, is currently a hot topic, as this approach would be more efficient and cost-effective for many of the groups involved. Although this strategy seems very promising, it comes with its own challenges. In this article, the authors discuss the barriers that are slowing the progress of drug repurposing and also give some potential solutions that can be used to address them.
One of the difficulties that researchers face is gaining comprehensive access to information regarding repurposing resources, as this collection of initiatives, funding, and collaborations are scattered widely and disorganized. A potential work around would be to have a drug repurposing toolbox that holds all this information in one place for scientists to access. Other barriers that many face are associated with navigating financial and regulatory incentives and evaluating the efficacy and safety of these existing drugs for different purposes. Possible solutions to these challenges could be creating funding opportunities that specifically target drug repurposing matters and enforcing data publication to help with the road to clinical trials for existing drugs with new directions, respectively. Lastly, the authors discuss obstacles tied to the clinical utilization of repurposed drugs. Companies commonly get stuck on the idea of changing the label of the repurposed drug before getting it out to patients, to which the authors propose the ‘label change last’ strategy. With this approach, the repurposed medication can be distributed to patients quicker and be more widely applied in an efficient manner. Overall, the drug repurposing approach has a lot of potential with many of its barriers in the process of being addressed, which holds a lot of promise and progression for the future of therapeutics. To read more about this article, check out the link below!
How AI may hold the key to faster rare disease diagnosis
With hundreds of millions of people affected by one of more than 7,000 known rare diseases worldwide, the rare disease community doesn’t seem so rare anymore as the cumulative impact is quite massive. As discussed earlier in this week’s #ScienceSaturday, while many are living with different rare diseases, the challenges they face collectively as a community are similar. Another common obstacle that many with rare diseases share is getting the correct diagnosis in a timely and accurate manner, which is essential to their future health and wellbeing. The reality is that many are initially misdiagnosed and have to wait years before finally arriving at the correct rare disease diagnosis, resulting in delayed treatment and management. Recognizing that this is a major challenge that drastically affects the health of patients, scientists are dedicated to finding ways to address this issue.
With the increase in technological advancements, scientists are looking to use artificial intelligence (AI) to help doctors link patient symptoms to those that may represent a rare disease. The hope with this method is that it will quicken the process of arriving at an accurate diagnosis. Additionally, researchers are interested in developing digital platforms run by multifactorial machines that can analyze patient symptoms and genetic data to help with the diagnosis determination. On top of the aid from technology, scientists are also pushing for increased sharing of patient data to increase the amount of data being analyzed, which will beneficially complement these technological systems at play. By implementing AI technology and encouraging large-scale collaborations, researchers, clinicians, and scientists are hoping to combat the challenges that many rare disease patients face when trying to get an accurate diagnosis. To read more about these efforts, check out the article below!