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NIH grant 1R01FD008873-01: Natural history of KIF1A associated neurological disorder
Institute: {'code': 'FD', 'abbreviation': 'FDA', 'name': 'Food and Drug Administration', 'admin_org_id': '12500799', 'admin_funding_url': ''}. PI: Wendy K Chung. Award: $599239.
Start: 2026-09-25T00:00:00.
Abstract
KIF1A-Associated Neurological Disorder (KAND) is a rare, highly phenotypically heterogeneous
neurodevelopmental and neurodegenerative condition caused by heterozygous mutations in the KIF1A gene.
While there are no current FDA approved disease-modifying therapies for KAND, we have an n-of-1 treatment
for the first KAND patient using a gapmer ASO that shows great promise. Due to the design of the ASO
(targeting a common polymorphism in cis with the mutation), approximately 25% of KAND patients could be
treated with the same ASO. To extend this treatment to other patients, the natural history of the disease, by
genotype, must be studied longitudinally to identify robust, sensitive outcome measures. We have preliminary
data from 311 patients, largely based on cross-sectional online questionnaire data, demonstrating that clinical
severity and disease course are mutation-dependent. By partnering with KIF1A.ORG, a large patient advocacy
partner devoted to KAND, we will enroll and characterize patients by genotype to establish phenotypic course,
and select phenotypic endpoints for future FDA trials.
This will be done with three Aims. Aim 1. We will characterize the natural history of KAND with data
abstracted from medical records and online questionnaires. These data include neurodevelopmental,
motor and cognitive function, vision/optic nerve atrophy, seizures/electroencephalograms (EEGs), brain
imaging, and quality of life in at least 200 patients. Aim 2. We will characterize the natural history of KAND
with longitudinal in-person assessments. This will be done in 60 patients using gold-standard assessments
of cognitive function, motor function, vision/optic nerve atrophy, and quantitative EEG and blood-based
biomarkers of neuronal degeneration. Aim 3. We will validate a remote assessment battery with
longitudinal measures. Remote data collection from at least 60 patients will include cognitive and
speech/language assessments, parental reports, actigraphy biosensors, and number of falls. The same
patients will be assessed in Aims 2 and 3 so that we can validate the remote measures. In all aims, clinical
severity and disease progression will be analyzed by KIF1A genotype incorporating single molecule in vitro
phenotype. We will build analytical models to predict clinical trajectories.
These natural history studies will define the course of disease and its severity, particularly in relation to specific
mutations, guiding design of clinical trials for KAND. Additionally, validation of remote assessments can be
applied to other neurogenetic disorders. We will seek funding through NIH grant mechanisms (R01 and U01)
for KAND ASO trials.document fetched 2026-10-04 02:43