#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
MUTATION OF SPASTIN AFFECTS MICROTUBULE DYNAMICS THROUGH DIFFERENTIAL DISTRIBUTION
With KAND causing an array of medical complexities, there are many signs, symptoms and diseases associated with this disorder. One of these is Hereditary Spastic Paraplegia (HSP), which is characterized by weakness and stiffness of the legs that result in gait abnormalities and limited range of motion in the lower extremities. In more than 40% of reported accounts, mutations in SPG4, a gene that encodes spastin, is the cause of HSP. Spastin is a protein that cuts microtubules into segments and is involved in a range of regulatory processes and neuronal development. Because of this, mutations within this gene disrupt and change its function, resulting in the health problems seen in patients with HSP.
In this paper, researchers are curious to explore the effect of a common spastin variant, C413Y, on microtubule stability to provide us with a model basis for future spastin studies regarding cleavage and its internal mechanism. From the data collected, this paper shows that the C413Y variant displayed a decreased ability to cut microtubules. Researchers suggest that this mutation may have caused a change in the overall protein structure of spastin, leading to its loss of function in stabilizing microtubules through segmentation. These insights give us a new approach to creating a rat HSP model to study ideas for future diagnosis and treatment. As we are learning more about the different clinical symptoms experienced by KAND patients, we are also advancing our understanding in creating potential therapies to address the complications that arise from these mutations. To read more about how C413Y affects microtubule dynamics, check out the article below! If you’d like to learn more, take a look at this video and follow the story of Jason, an adult with HSP.
Rare Disease News
NEW STRATEGY TO ACCELERATE DIAGNOSIS AND IMPROVE TREATMENT OF RARE DISEASES
Each day, new strides are made in the rare disease communities around the world to raise awareness and accelerate research to find treatments. As of recent, the UK has set up a new initiative called the Rare Disease Framework that is dedicated to improving the lives of more than 3.5 million people diagnosed with rare diseases by using a new strategy designed around the experiences of those in this community. Four nations (England, Wales, Scotland, and Northern Ireland) signed and agreed to carry out this framework to prioritize speedier diagnoses, better coordination of care, increased awareness amongst healthcare professionals, and more accessible drugs, treatments, and specialist care. As new conditions are being identified and more people are being diagnosed as a result of research advances, this creation of the Rare Disease Framework is a major step forward for the rare disease community as a whole and we hope new initiatives worldwide will follow suit! If you would like to read more about this, check out the article below.
“I want the experiences of those living with a rare disease to shape the priorities of [the] government to make sure our policies work for them. We can harness the potential of new technologies, including genomics, to support earlier detection and faster diagnosis of disease, tailor and target treatments.”
Health Minister, Lord Bethel
CURRENT SCENARIO OF THE GENETIC TESTING FOR RARE NEUROLOGICAL DISORDERS EXPLOITING NEXT GENERATION SEQUENCING
A long-standing challenge that is still prevalent in the rare disease community is the speedy determination of a diagnosis that explains the cause responsible for the disorder. To combat this, advancements in genetic testing over the past years have helped expand the approach to detecting rare mutations in neurological disorders, with next generation sequencing (NGS) being at the forefront. This review dives into the current state of NGS, a method used to identify sequence variants on an unprecedented large scale in genetically heterogeneous diseases, by discussing the advantages and limitations that surround it. In doing so, we gain a better understanding of how this approach opens a new age of molecular diagnosis, brings value in helping patients receive precise and tailored treatment, and addresses the gaps to improve accuracy and efficiency.
Evolving from first generation Sanger sequencing, second generation NGS consists of three different approaches: targeted sequencing, whole-exome sequencing, and whole-genome sequencing. They differ in yield, detection, and depth of coverage and the review focuses in on each strategy’s pros and cons and details the workflow of NGS data analysis from raw data conversion to data interpretation and classification. To conclude, the article emphasizes the important benefits the NGS brings to improving the approaches that can reduce diagnosis time for patients with rare diseases, which ultimately leads to advances in gene therapy and treatment plans. As scientists are working to bridge the gap seen in second generation sequencing, there is talk of third generation platforms to overcome these issues! To learn more about NGS and the progress of gene therapy, click on the article below.