#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.
2023 KAND Family & Scientific Engagement Conference Wrap-up
A happy Labor Day weekend to our readers in the US!
It’s hard to believe that a month ago KAND families were arriving in New York City from all around the world to participate in the KOALA trial-readiness study and attend our 2023 conference. I’d be remiss not to state my gratitude to everyone who joined us for this exceptional event; our families, researchers, and clinicians created a culture of empathy, curiosity, and determination that was second to none; we’ve been integrating all we’ve learned and are hard at work building on our conference momentum with our Research Network.
You can watch all of the sessions at our conference page; over the coming weeks we’ll be highlighting and creating resources from these talks, and discuss what they mean for the KAND community moving forward.
KIF1A-Related Research
Spastic Paraplegia Type 30 Associated with Levodopa‐Responsive Parkinsonism
When we talk about KAND as a neurodegenerative disorder, it’s often in the context of function loss in KAND kiddos. But as we learn more about adult cases and milder phenotypes, it’s important to consider potential consequences of KIF1A mutations as individuals age. In this week’s case study, neurologists assessed a woman with a KIF1A mutation and Spastic Paraplegia Type 30 (SPG30) diagnosis who developed parkinsonism in her early 50s.
Disclaimer
This isn’t a study that shows KIF1A mutations cause Parkinson’s Disease. We also don’t have enough information to know whether the KIF1A mutation contributed to parkinsonism with aging, or if this was the convergence of two different disorders. As the authors state, “It is possible that the patient developed idiopathic Parkinson’s disease at age 53 that caused decompensation of her longstanding SPG30.”
Parkinson…ism?
So what is parkinsonism? Many neurodegenerative disorders have been historically described by symptoms; as our understanding of neuroanatomy advanced, we were also able to start describing specific circuits that degenerated. In Parkinson’s for example, a key disease mechanism is degeneration in the substantia nigra, a region of the brain that uses dopamine to drive voluntary movement.
But over time it’s become clear that these circuits can be lost or compromised due to a variety of underlying genetic causes or biological mechanisms; parkinsonism refers to a broader umbrella of disorders causing motor symptoms like those observed in Parkinson’s Disease.
The Study
In this case, the clinicians used a technique called a Dopamine Transporter Scan, which labels dopamine transporters on neurons, to identify a loss of those neurons in the substantia nigra, an observation in Parkinsonism.
Here’s a brief excerpt on the patient’s symptoms:
She described a sensation of being “dragged forward” with her knees pulled toward one another. She found it difficult to place her heels on the ground while walking, preferring to walk on her toes. At her first presentation she also reported urinary urgency and nocturia without incontinence. Her arm function, speech, hearing, and vision were unimpaired.
Gallagher et al. 2023
Based on her symptoms, the clinicians treated her with levodopa, a dopamine precursor that has been used to treat parkinsonism in other types of spastic paraplegia, and her movement improved.
Potential KIF1A mechanisms
As I said in the beginning, we don’t want to jump to the conclusion that KIF1A mutations contribute to parkinsonism, but there may be connections. One potential role of KIF1A in the substantia nigra is delivering a cargo called vesicular monoamine transporter‐2 (VAMP-2), which helps concentrate dopamine into vesicles.
As we characterize our preclinical KAND models over time, investigating the role of KIF1A in the substantia nigra and dopamine may uncover more information about motor dysfunction in KAND. We can also learn more from other spastic paraplegia subtypes that experience parkinsonism.
Rare Roundup
From Bedside to Bench and Back
Second only to KOALA enrollment, the biggest success of our conference was the open dialogue and collaboration between our families and scientists. We’re privileged to be riding a cultural wave that integrates patient voices into the research and clinical processes. This change didn’t happen overnight, it’s been decades in the making at great cost and sacrifice. Tania Simoncelli, vice president of Science in Society at the Chan Zuckerberg Initiative, shares her perspective on the history of patient-centered medicine, and where we can take it from here.