I’ve heard that there are some people that are supplementing with fisetin, and that it has a positive impact on some variants? How does this work, and is there any recommended protocol floating around? Does anyone have any anecdotes to share?
Hi Cory,
We do have several families that are taking fisetin supplements, specifically bio-fisetin by Life Sciences which is optimized to be more bioavailable. Angie may have more info on what dosage they’ve settled on.
The use of fisetin is based on a study that found that in a worm model, fisetin could improve the movement of human R11Q KIF1A, essentially by fitting into the pocket that the mutation misshaped.
Structure-based therapies tend to be mutation-specific: Each variant causes unique structural changes in KIF1A, and fisetin fits into a specific pocket that may not be affected by other mutations. While not a peer reviewed study, undergraduate projects coordinated by Dr. Shi at Stanford found that fisetin did not significantly improve function in a few other variants including S274L and L275P.
There are other variants that affect the same pocket as R11Q, but more research needs to be done. Here’s a quote from the study I linked:
“Caution is crucial when considering the use of fisetin or any other dietary supplement for KAND patients… some KAND mutations have been shown to result in overactive KIF1A. Even though our experiments indicated that fisetin exhibited no discernible impact on wild-type KIF1A motor dynamics… molecules[like fisetin] that stimulate the motor might have a dual effect, potentially jeopardizing organism health if they provoke excessive motor activity.”
If you do decide to try fisetin, please talk with your doctor first, and keep an eye out for any changes, positive or negative.
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Hi Cory, my son has the R11Q variant and after this publication came out we started taking 44.5mg daily of Biofisetin from Life Science. It’s super early science showing positive effects in worm models, and we don’t know how much to take or how much crosses the blood brain barrier. But we take it daily anyway. I do believe I have seen very mild improvement in bladder and bowel control, and perhaps a very slight improvement in toe drag when he is tired (less falling and tripping). Again, lots of bias because I want it so badly to work, but it hasn’t shown anything dramatic at all. Other R11Q patients have taken it as well, so getting their response would be interesting.
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