#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

Investigating KIF1A mutations in a Taiwanese cohort with hereditary spastic paraplegia

In the last 6 years, our KAND family community has grown from 50 known patients to over 500, but it’s likely the actual number is far greater. This is because KAND is a genetic disease – it is defined by mutations in the KIF1A gene. Without genetic testing, patients are likely to be diagnosed according to symptoms: epilepsy, intellectual disability, and hereditary spastic paraplegia (HSP) are all symptom-defined disease groups that are sometimes caused by KIF1A mutations. Performing genetic screens on these groups is the only way to learn about the prevalence of KAND, its inheritance pattern, and its heterogeneity – how it manifests differently in different people.

In this week’s article, researchers from Taiwan tested for KIF1A mutations among HSP patients. Out of 242 patients tested, 3 were found to have KIF1A mutations: Two of these mutations (R316Q and G321D) are already associated with KAND, while the third (E19K) is a novel mutation in the motor domain that hasn’t been characterized as KAND-causing. The authors then performed clinical examinations assessing movement, the speed of electrical signals in neurons, and changes in brain structure.

For each of these three people, the authors were able to identify family members with the same KIF1A mutations who had HSP symptoms. There are over 100 known mutations in the KAND family community, so we expect heterogeneity – the types of symptoms and their severity can vary. But clinical examinations of the families in this study highlighted that even family members carrying the same mutation may experience different disease progression. In one family, the parent began experiencing movement issues at the age of 40, while their child’s movement was impaired at 3 years old. 

We know our picture of KAND is still incomplete, and uncovering its complexity is an invaluable step toward better treating the community as a whole. We’re grateful to the authors for this clinical genetic study for providing answers to HSP patients and adding to our understanding of KIF1A mutations.

Rare Roundup

New consortium to ensure access to gene therapies for children with rare diseases

A hurdle for therapeutic development for rare diseases is their rarity – while publicly funded preclinical research can uncover many promising treatments, profit-driven systems thrive on large populations, creating a bottleneck at the expense of patients. But collectively rare disease patients represent a massive community, so pooling resources for rare disease research is a necessity. This week, London’s Great Ormond Street Hospital for Children launched a new group of clinicians and researchers called AGORA (Access to Gene Therapies for Rare Disease), whose mission is to identify and lower hurdles to sustainable treatment development, and create a non-profit model for rare disease drug development and marketing. AGORA will begin by focusing on rare genetic immune and metabolic disorders before expanding their efforts.

New uses for old drugs? Every Cure offers hope for people with rare diseases

The development of new drugs is an ever-expanding effort to improve the lives of patients without treatment. But biology is complex, and even drugs intended to treat one specific disease can be invaluable to other disorders – our community relies on such drug repurposing. Because established therapeutics have been studied for safety, drug repurposing can also shorten the timeline to approval, which is being taken advantage in projects by our partners at NeuCyte and the Murdoch Children’s Research Institute.

Every Cure, a new non-profit co-founded by Dr. David Fajgenbaum and Dr. Grant Mitchell, aims to raise $55 million dollars to create algorithms that identify generic drugs as likely candidates for treating other disorders and conduct clinical trials on the most promising opportunities. This repurposing strategy has the potential to save both money and precious time for finding treatments for under-served rare disease communities.

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