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

KIF1A-Related Research

Paroxysmal fast activity is a biomarker of treatment response in deep brain stimulation for Lennox-Gastaut syndrome

To test a new therapy for a disease, you need to be able to measure its effects. Epilepsy is a disease causing abnormal electrical activity in the brain; when excessive activity reaches a certain threshold and causes symptoms, we call that event a seizure. There are many types of seizures, and you can read a brief review in our previous post.

A common measurement for epilepsy clinical trials is seizure frequency, which is reported by patients or caregivers in a seizure diary, or measured during long-term Electroencephalogram (EEG) monitoring.

This is a challenge because even when a patient is known to have epilepsy, seizures may occur at any time, for an unpredictable amount of time, and can be quite subtle – simply put, you might not catch them all. Seizure diaries and EEGs may underestimate the actual number of seizures, and inaccurate data makes it harder to assess treatments.

But an epileptic brain doesn’t always go directly from normal activity to seizure-inducing – there may be other abnormalities that happen between seizures and can be captured more reliably by EEG. What if we could measure those abnormalities and use that as an indicator for epilepsy treatments?

In this week’s article, researchers investigated the relationship between EEG measurement of electrical activity between seizures, and the reported frequency of seizures, in Lennox-Gastaut Syndrome, a childhood-onset epilepsy.

The patients in this study were adults undergoing Deep Brain Stimulation (DBS) treatment. Deep Brain Stimulation uses a surgically implanted device that detects abnormal brain activity and counteracts it with electrical pulses, like a pacemaker for the brain.

Over the year-long study, patients were assessed every three months at different stages:

  • Baseline: Before the DBS surgery
  • Pre-stimulation: After the surgery but before the device was turned on
  • Blinded: Half of patients had the device turned on, and half didn’t.
  • Unblinded: All patients had the device turned on.

At each stage, researchers collected 24-hr EEGs that measured both seizures, and a type of electrical activity between seizures called generalized paroxysmal fast activity (GPFA). This activity can be measured even when seizure symptoms aren’t present, but hasn’t formerly been used as an indicator of seizure activity.

They found that the number of GPFA events correlated with the number of seizures patients experienced, measured both by EEG and seizure diaries. The GPFA also responded to treatment – when patients were receiving DBS, their GPFA events decreased alongside seizure frequency.

This could provide an easier avenue for assessing treatments for Lennox-Gastaut Syndrome, because we can observe it even when a patient isn’t actively experiencing seizures.

So how does this apply to KAND? There are some limitations to the study: We don’t have a firm understanding of GPFA in KAND epilepsy, this study excluded absence seizures which are common in KAND, and it didn’t test small molecule or gene therapies. But this approach of finding non-seizure indicators of epilepsy could be incredibly useful for our community, and is a key reason for our EEG study – by looking at electrical activity across a large number of patients, we may be able to find similar markers that will make it easier to test therapeutics.

Rare Roundup

Govt decision to remove tax on drugs & food to treat rare diseases could benefit 70-90 million Indians

Health equity relies on making treatments accessible to the people that need them. This has been a historic challenge for rare disease communities, because treatments for small populations are often quite expensive. Every step toward easing the financial burden of disease treatment is worth celebrating, especially when it happens in the second most populous country in the world. This week, India’s finance ministry made the historic choice to remove import taxes for medications and foods that are used to treat rare diseases. This can benefit rare disease patients in India, and therapeutic developers who provide free or reduced-cost treatments for these patients.

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