KIF1A associated neurological disorder (KAND)

Father shares daughter’s rare neurological disorder, partnership with Murdoch research center

KIF1A.org founder Luke Rosen discusses his daughter’s battle with a rare neurological disorder and the Murdoch Children’s Research Institute’s work to advance potential treatments on ‘Fox & Friends.’

KIF1A Associated Neurological Disorder (KAND) is a rare, progressive neurodegenerative disorder often described as a form of childhood dementia that currently has no cure, but researchers at the Murdoch Children’s Research Institute (MCRI) in Australia are working to change that.

"[Their research] is helping all of the kids, which is really incredible," said Luke Rosen, founder of KIF1A.org, whose daughter Susannah was diagnosed with the disorder at age 2.

"And the folks at Murdoch, I say they're extended family to us, and they really are."

KAND is a severe and progressive condition. Children can experience seizures and, over time, lose cognitive function, motor skills and vision. The disorder affects each patient differently, often making it difficult to diagnose.

Rosen said what sets MCRI apart is its personal approach — with researchers taking the time to truly know the families they’re trying to help.

"The first thing [a researcher] said to me is, 'How's Susannah? How's she doing?' And he really got to know our family, and he travels and so does their whole team... to our yearly Scientific and Family Conference, so they really get to meet all the families."

A new Fox Nation special spotlights MCRI’s work, as well as families like the Rosens who are working with researchers to treat the debilitating disorder.

Rosen has since dedicated his life to advancing research and finding treatment options. He works closely with MCRI in an effort that is already showing promise.

Susannah was among the first patients to receive antisense oligonucleotide (ASO) therapy, and her family says they’ve seen meaningful improvements in her condition.

While the treatment is not yet approved in Australia, Rosen continues working with doctors to expand access with the hope that, eventually, families won’t have to travel for care.

"Their research is really translational research that helps everybody," Rosen said.

"While we don't have a therapeutic yet from Australia, they're really working hard to develop it, and they're accelerating that entire process. What's special about Murdoch is they work in multimodalities, so there's gene therapy and then traditional drug development, and then they work non-sequentially, and they are just trying to throw as many shots on goal as we can for the kids."

"Hope Starts Here," hosted by Fox News' Benjamin Hall, is available now on Fox Nation.

Taylor Penley

https://www.foxnews.com/media/researchers-race-treat-rare-childhood-dementia-cure-giving-families-new-hope

Lin Q, Verden D, Christodoulou J, Gold WA, Kaur S. KIF1A-associated neurological disorders: therapeutic opportunities and challenges. Eur J Hum Genet. 2025 Nov 27. doi: 10.1038/s41431-025-01978-8. Epub ahead of print. PMID: 41310149.

Abstract

KIF1A-Associated Neurological Disorder (KAND) is a rare, progressive neurodegenerative condition caused by variants in the KIF1A gene, which encodes a kinesin-3 motor protein essential for anterograde axonal transport of synaptic vesicles, dense core vesicles, and organelles in neurons. KAND comprises a broad spectrum of overlapping neurological phenotypes, including hereditary spastic paraplegia, intellectual disability, peripheral neuropathy, optic nerve atrophy, epilepsy, and progressive motor decline. Pathogenic variants in KIF1A disrupt the balance of intracellular transport and neuronal signalling through diverse mechanisms, manifesting with highly variable disease onset, severity, and clinical progression. Although advances in genomic testing have improved diagnosis, reported KAND cases remain concentrated in developed countries, highlighting ongoing global inequities in access to diagnosis and care. At present, no cure exists for KAND; treatment is limited to symptom management. A deeper understanding of KIF1A function, supported by the development of robust cellular and animal models, is critical for therapeutic development. This review summarises the clinical and molecular features of KAND and highlights current and emerging strategies aimed at slowing disease progression or correcting its underlying causes. We emphasise the urgent need for targeted treatment strategies addressing the heterogeneity of KAND.

Chen Z, Chai Y, Guo Z, Fu X, Li W, Zhang J, Ou G, Wang H. Allele-specific conformational rescue of KIF1A T99M by genetic suppressors in a C. elegans model of KIF1A-associated neurological disorder. J Cell Sci. 2025 Oct 1;138(19):jcs264216. doi: 10.1242/jcs.264216. Epub 2025 Oct 14. PMID: 40964787.

Abstract

KIF1A-associated neurological disorder (KAND) arises from mutations in the microtubule motor KIF1A, disrupting synaptic vesicle transport. Here, we investigate the pathogenic T99M substitution in the P-loop of KIF1A, which induces steric hindrance, impairing ATP/ADP coordination and motor activity. Using CRISPR-engineered Caenorhabditis elegans expressing the homologous UNC-104(T95M) mutation, we conducted forward genetic screens and identified recurrent intragenic suppressors (T95V and T95I; T95V/I) that restored animal motility and synaptic vesicle distribution. Molecular dynamics simulations revealed that replacing the methionine residue with valine or isoleucine residues alleviated steric clashes in the nucleotide-binding pocket and stabilized Mg2+-ATP coordination. Biochemical assays showed that T95V/I partially recovered microtubule gliding velocity and processivity, demonstrating that even modest motor reactivation mitigates neuronal dysfunction. Inspired by prior success showing that treatment with the plant flavonol fisetin rescues the effects of the KIF1A R11Q variant, we propose allele-specific conformational stabilization as a therapeutic strategy for KAND. Our findings highlight the structural plasticity of motor domains and provide a framework for precision therapies targeting pathogenic variants through genetic suppressors.

See: https://childnervoussystem.blogspot.com/2020/01/kif1a-mutations.html