KIF1A.ORG: research and therapeutic development

KIF1A.ORG was one of the recipients of CNF’s $10,000 RISING Tides grants in 2020.

KIF1A.ORG is a global community dedicated to improving the lives of those affected by KIF1A Associated Neurological Disorder and accelerating research to find a cure. Since their founding in 2017, KIF1A.ORG has worked closely with a dedicated team of researchers led by Dr. Wendy Chung at Columbia University. As a result of their collaboration, the scientific community has access to tools for therapeutic development, such as a patient registry and natural history study, animal models, iPSC lines and identified biomarkers.

COVID-19 abruptly revealed a weakness in the therapeutic development strategy. Located at the early epicenter of COVID-19 in the United States, Columbia University in New York City was forced to shut down wet labs and research activities, including critical KIF1A research at Chung Lab. As a result of this unprecedented disruption, KIF1A.ORG moved quickly to devise an emergency strategy to diversify their research partners and activities.

PDB ID: 1VFV Nitta, R., Kikkawa, M., Okada, Y., Hirokawa, N. (2004) KIF1A Alternately Uses Two Loops to Bind Microtubules Science 305:5684

While Chung Lab has resumed operations and remains their primary collaborator, KIF1A.ORG is now engaged with additional research partners to prevent total disruption to the organization’s research and development efforts moving forward. This is especially critical as we enter fall 2020, unsure if academic labs and universities will be forced to shut down again due to coronavirus outbreaks.

“Due to the degenerative nature of KAND, every day matters. While COVID-19 may bring parts of our world and lives to a halt, KIF1A will not stop robbing children of their ability to walk, talk, see—sometimes even eat or breathe, until we find treatment. Rising Tides funding provided by the Child Neurology Foundation made it possible for the KIF1A.ORG patient community to ensure critical KAND research continues to move forward despite academic research being disrupted by the COVID-19 pandemic.” – Kathryn Atchley, President of KIF1A.ORG

The Child Neurology Foundation Rising Tides grant in particular enabled KIF1A.ORG to partner with Albany Molecular Research Inc. (AMRI). AMRI is a distinguished contract research organization (CRO) with multiple locations and a range of services that support therapeutic development. Throughout the pandemic, AMRI has remained fully operational. After careful vetting and review of research proposals from multiple institutions totaling over $1,200,000, KIF1A.ORG launched the collaboration with AMRI in August 2020. The first project is an in silico docking study to support KIF1A.ORG’s drug repurposing therapeutic development strategy.

Through this project, AMRI will model the KIF1A crystal structure to understand the location and possible effects of known gain-of-function and loss-of-function mutations, and explore existing kinesin binding compounds. The first round of modeling will provide insight into assay design and strategies to pursuing additional mutations. The estimated completion date of the first round is mid-September at a cost of $4,100. At this point, KIF1A.ORG staff will consult with the Research Team to evaluate the results of the first round of in silico modeling to determine if the study warrants expansion into additional mutations (for an additional cost), or if they are ready to launch the second project with AMRI: an iPSC phenotyping study, to create cellular models needed to 1) test previously identified compounds and/or 2) conduct a high throughput drug screening.

Some of the children in the KIF1A.ORG community, in a “Meet our Superheroes” photo.

Despite the disruption caused by COVID-19, KIF1A.ORG turned an emergency into an opportunity to diversify their research partners and launch a drug repurposing program as part of efforts to bring treatment to this generation of KAND patients. The entire KIF1A.ORG community is incredibly grateful for the Child Neurology Foundation and their support of rare disease communities like ours, especially in these uncertain times.

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