#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.
This week we have a very special edition of #ScienceSaturday that highlights a handful of recent advancements from KIF1A.ORG Research Network members and more!
High-Resolution structures of microtubule-bound KIF1A and its pathogenic variant P305L
In many cases, traditional drugs are used to manage or treat symptoms: A patient is likely to need different drugs for epilepsy, spasticity, and attention deficits, even if all are caused by a mutation in KIF1A. But structural medicine works by developing treatments that work directly on a faulty protein.
Many KIF1A mutations cause disease by changing the shape of the KIF1A protein, and different mutations can change the shape in different ways. If we understood the exact way a mutant KIF1A is shaped differently from healthy KIF1A, we could make drugs that fit like puzzle pieces to fix the problems caused by that mutation.
It’s easier said than done for something as small as a protein: Most mutations change just one of 5,373 letters in the KIF1A gene, so the differences are subtle. The structure of healthy KIF1A is a decades-old question that hasn’t been resolved due to technological limitations.
In this week’s pre-print* article, researchers from the labs of Research Network members Dr. Arne Gennerich and Dr. Hernando Sosa resolved the structure of KIF1A as it walks along the microtubule. This provides us with new insights into how exactly KIF1A is able to move as quickly and as far as it does compared to other motor proteins.
The authors also resolved the structure of the KIF1A mutant P305L, a prevalent and devastating mutation. They were able to determine that structural changes in a part of KIF1A called the K-loop prevented P305L KIF1A from binding to the microtubule properly. The hope is that this K-loop could be a therapeutic target for structure-based drugs, and that this process can determine the structure of other KAND-associated mutations too!
*What’s a pre-print? Check out this #ScienceSaturday post to learn more!
The Future of Rare Disease Care Depends on Thinking Globally
For rare disease communities, numbers matter a lot – each person included adds to the chances of better diagnostics, therapeutics, and treatment pricing. And because rare diseases don’t know borders, most rare disease communities are global communities; integrating international participation in clinical research can help rare disease groups get the numbers they need more quickly.
Creating global approaches to rare disease research and care is a massive task that spans cultural, logistical, and policy barriers. Dr. Harsha Rajasimha, founder of IndoUSrare, is committed to removing these barriers to encourage integration of rare disease patients in the United States and India. These efforts could significantly increase the number of patients able to participate in clinical trials, and serve as a template for other international efforts to treat rare diseases.