#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 Volunteer Aileen Lam and Chief Science Officer Dr. Dominique Lessard. Send news suggestions to our team at impact@kif1a.org.

Recent KIF1A-Related Research

Monoallelic KIF1A‑related disorders: a multicenter cross sectional study and systematic literature review

This week we are featuring a group of Italian researchers who conducted a multicenter study focused around patients with heterozygous KIF1A mutations, presenting with spastic gait or complex neurodevelopmental disorders. What exactly does this mean? It means that the patients identified for this study were from more than one medical institution (multicenter), had a mutation in only one copy of the KIF1A gene (as is commonly observed in KAND patients), and also presented clinically with muscle tone irregularities and other symptoms related to neurological disorders. Additionally, this group conducted a literature review to compare their findings with previously-reported KIF1A-related phenotypes.

This study took a comprehensive approach, aiming to “investigate the full genetic, clinical and neurological spectrum of KIF1A-related disorders.” Of the 28 patients observed, 17 mutations occurred within the motor domain of KIF1A with no correlation found between disease severity and mutation location. Additionally, this study performed muscle biopsies, showing that 40% of patients had oxidative damage and impaired lipid (fat) metabolism in skeletal muscle. This tissue-level analysis of muscles in KIF1A patients is a new type of information for our community, and is very valuable to help us understand some of the molecular impacts of KIF1A mutation in the neuromuscular system. Want to learn more or brush up on the basics of genes and alleles? Check out the video below!

Rare Roundup

New Mini-CRISPR Systems Could Dramatically Expand the Scope of Gene Therapy

The introduction of CRISPR genomic editing technology has revolutionized our thinking around therapeutic treatment options for a vast number of diseases and disorders. For many in the rare disease community, CRISPR and similar genomic editing techniques are viewed as the “holy grail” of treatment for diseases with a known genetic cause. However, not unlike other therapeutic options, CRISPR technology has its translational challenges and limitations. One of these challenges relates to the size of the CRISPR machinery that must be delivered to cells to conduct genomic editing. Luckily, three research papers released last week have revealed a potential workout for this problem. In these papers, researchers have identified CRISPR machinery parts that are much smaller than earlier prototypes and can fit into adeno-associated viral vectors (AAVs); AAVs are considered the “gold standard delivery system for in vivo gene therapies.” While these studies are still early in development, they importantly provide potential solutions to existing issues with CRISPR delivery to cells. If successful, this approach could greatly increase the capabilities of CRISPR to treat human disease. Want to learn more about how CRISPR technology can be delivered into cells? Check out the video below!

First specific drug therapy for a severe early form of epilepsy

Here’s a success story we hope to see repeated in the KIF1A community soon! Researchers in Germany have identified a multiple sclerosis drug that can be repurposed to treat a severe form of epilepsy caused by mutations in the KCNA2 gene. In a small study involving 11 patients, seizures were reduced or eliminated in 9 patients. This resulted in additional positive outcomes for patients: “The patients were generally much more alert and mentally fitter in everyday life. Their speech also improved after starting the drug treatment.” Researchers note that the drug is not suitable for patients with certain mutations of the KCNA2 gene. Just like KIF1A mutations, KCNA2 mutations can cause different types of dysfunction. While some KCNA2 mutations restrict activity of potassium channels, this drug works on mutations that increase activity of potassium channels. The KIF1A community is likely to see these kind of mutation-specific treatment options available as researchers pursue a variety of therapeutic approaches.

A promising point to take away from this success story for KCNA2 is how therapeutic development efforts are possible for even the rarest of disorders. There are about 50 known cases worldwide of people affected by KCNA2 mutations. While it takes a lot of time and money to develop new treatments for any disease, drug repurposing is a powerful opportunity for rare disease communities to overcome hurdles to traditional drug development.

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