Lab News

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Congratulations to Katie Lam for her acceptance into the UCSD Biomedical Sciences PhD program. We know Katie's talent will shine in this next phase of her training and are grateful for all of her hard work advancing CRISPR therapies in our lab. Congrats Katie!


We are proud of Isabelle Fisher who is joining the her dream school as part of the UCSF Medical School Class of 2028! She starts in the summer of 2024. Way to go Isabelle!


Tau team in their natural habitat! 


Greg Mohl was awarded the Live Like Lou Postdoctoral Fellowship for his work developing novel CNS CRISPR delivery reagents. Congrats Greg!


Congratulations Greg Mohl for winning the poster competition at the UC-LLNL ALS symposium.


 

Our latest work has been published!

Reversal of C9orf72 mutation-induced transcriptional dysregulation and pathology in cultured human neurons by allele-specific excision.

The Clelland lab has figured out how to correct the C9orf72 gene in a way that prevents pathology, an advance for CRISPR therapeutics for ALS and FTD.

Attempts to silence the mutation did not correct pathology because of antisense gene expression, perhaps providing insight to the failure of the C9-ASO trial. Removing the repeat expansion from the genome using allele-specific or intronic excision corrected all pathology. We are excited to advance this therapy to in vivo testing and toward the clinic.


 

Using weights to temper tremor 

March 21, 2024

I am grateful to Bill Drake who generously shares his experience using weights to temper essential tremor so that others might try this homebrew to see if it works for your ET.

The wrist weights Bill uses can be found on Amazon by searching “wrist weights for tremor” (https://www.amazon.com/s?k=wrist+weights+for+tremors&hvadid=580671224132&hvdev=c&hvlocphy=1014226&hvnetw=g&hvqmt=e&hvrand=14527449272998719163&hvtargid=kwd-28118138840&hydadcr=8213_13498061&tag=googhydr-20&ref=pd_sl_yyky61k9v_e)

Bill’s tip for wrist weights: “The ones I bought have a series of smaller weights on the band. I can remove one or more to adjust the amount of weight to match the tremor. However, I found that my response did not need this kind of fine resolution in the amount of weight and simply put the full band on when tremors are present.”

Bill likes these finger weights (https://www.advantagemedical.com/products/finger-weights-5pc/). “I chose these because I could add or take away some of the weight slugs to match the tremor situation. So far for me, all three slugs are working.”

Bill shares how he came to his finger and wrist weight solution that is working well. He writes:

I am an electrical engineer by training and had career experience with servos and robotics. So when the essential tremors started I got to thinking about how the body works and correlated with the servo experience.

In a servo loop something provides a signal to the control dictating the position for the servo to assume. Locally, the servo driver monitors the position of the servo end effector and when the incoming

position directive disagrees with the present position of the effector, the servo driver signals the positioner to drive the effector toward the new position while monitoring the new location as it progresses. Each of the signals travelling around the "servo loop" has delays - in electronics it is about a nano second per foot. If the position feedback signal delay is longer than the driver signal, the servo driver can overdrive the positioner. So by the time the position signal gets to the driver, the effector has gone past the desired position. The driver then will send a new control signal to the driver to correct the position (reversing the direction of the previous control signal). If the delays again cause the driver to overdrive the position, oscillation will occur as the system keeps overdriving the position alternately.

Potential solutions are to increase the speed of the position feedback signal - or to slow down the positioner control signal. Another solution is to modify the time constant of the effector to slow down its movement.

OK - so what to do about the tremors? Modifying the signal speed or control speed are difficult. One of the solutions in robotics is to add weight to the effector, this makes it harder for the driver to move the effector and results in slowing down the movement of the effector, allowing the position sensor signal to "catch up" before the control overdrives the position. Result is that the oscillation (tremor) stops.

So I ordered some wrist and finger weights from Amazon. I found I had two slightly different tremor conditions. Sometimes it was the wrist doing the shake other times the fingers. Using the matching weight to the tremor solved the problem. For me, the weight made it slightly harder for the muscle (positioner) to move the wrist or finger and allowed the nerve with the position signal to catch up in time to not overdrive the position.

The weight solution is sufficient for me at this time and has enabled fine motor work to resume.

Special thanks to Bill for sharing this insightful and cost-effective solution. Please let us know if this works for you!

 

Wishing you straight lines and an unspilled cup of tea or coffee!

Claire