#ScienceSaturday posts share exciting scientific developments and educational resources with the KAND community. Each week, Dr. Dylan Verden of KIF1A.ORG summarizes newly published KIF1A-related research and highlights progress in rare disease research and therapeutic development.

KIF1A-Related Research

Hidden behavioral fingerprints in epilepsy

Epilepsies are disorders of electrical activity in the central nervous system. When the brain’s electrical activity changes enough to cause noticeable changes in behavior, we call that event a seizure.

Our ability to identify and categorize seizures has grown considerably in recent decades, but there are limitations; clinicians are more likely to notice longer or more drastic seizure-associated behaviors, which may miss more subtle neurological events that impact patients. Finding new ways to identify epilepsy-associated ticks could be a major step toward understanding epilepsy subtypes, providing earlier diagnosis, and assessing anti-epileptic drugs.

In this week’s article, researchers used motion capture cameras to track seizure-prone mice. By analyzing these videos with machine learning, they identified small units of movement called “syllables”: These syllables often lasted less than a second, shorter than could be reliably identified by a human experimenter.

By using machine learning, researchers can identify subtle movements that may be associated with epilepsy. By identifying short and subtle changes in movements, we may be able to characterize epileptic events with more precision. From Gschwind et al. 2023, Neuron.

To test this system, the researchers recorded movement syllables in healthy mice, as well as mice with chemically or genetically-generated seizures. They tested if their program could sort epileptic from non-epileptic mice using these syllables of movement. It outperformed human experimenters and models that relied on cruder measurements like average speed or distance moved, even when using recordings taken between seizures.

By recording so many types of movements, this analysis can build a “fingerprint” of movement. Rather than focusing on a single parameter, the researchers looked at how the overall fingerprint differed between epileptic and non-epileptic mice. This level of detail could be used to inform the choice between multiple anti-epileptic drugs; if a drug can make the epileptic mouse’s fingerprint closer to the healthy mouse, it might be a good candidate for further study.

This study was a proof-of-concept, but its principles could be applied to motion capture in epileptic humans. It’s likely that we underestimate the number of events experienced by many epileptic individuals; by increasing the sensitivity and reducing the bias of our assessments, we can find more targeted treatments more quickly.

Rare Roundup

Different US/UK Initiatives Each Plan to Sequence the Genomes of 100,000 Newborns to Identify Treatable Rare Diseases Undetectable to Standard Screening Tests

Our understanding of genetics has progressed rapidly in recent decades; many disorders that were solely diagnosed by symptoms are now known to be caused by specific genetic mutations. The expense of genetic testing and limited understanding of the human genome were bottlenecks in medicine; tests were ordered under specific circumstances, and results were limited to panels of predetermined genes – this means missed diagnoses, and in some cases treatments, for children with rare diseases

As our glossary of genetic disorders grows and our techniques advance, there have been efforts to integrate more advanced gene sequencing more regularly for infants. Many rare genetic disorders are treatable, and earlier diagnosis could make those treatments more effective.

We discussed the Newborn Genomes Programme in the UK last December, which seeks to perform genome sequencing on 100,000 newborns. In parallel, the Guardian (Genomic Uniform-screening Against Rare Diseases In All Newborns) program led by KAND champion Dr. Wendy Chung began in the US last year, with a similar goal of screening 100,000 newborns. The study will utilize whole genome sequencing to search for 160 rare diseases that are currently curable, and parents can opt in to search for another 100 disorders that may be amenable to speech or physical therapy.

This is a major step toward normalizing genetic testing for newborns so we can provide targeted treatments for rare diseases as early as possible.

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