Hope this posting finds you well. I am logging back in in preparation for my third DBS surgery eval coming up this Friday at Mayo Clinic Jacksonville. As exciting as it is, I have angst at the thought of going off all my meds once again. I've had Early Onset Parkinsons since Jan 2009 and have only gone completely off my meds about 5 times total. Last August it was for 24 hours for my social security disability eval. Previous to that was November 2016 for the second DBS eval at UofMiami which resulted in surgery scheduling but my relocation to central Fla cancelled it.
Here we are again - my third surgery eval off meds. This time they only requested I be off for 8 hours but the increase in the severity of my disease between Nov 2016 to Aug 2017 was striking. We are now 7 months later than that and I have a constant low to medium velocity tremor (that only subsides while in deep sleep) I have become accustom to that I didn't have at either time ON my medications. What is in store for me this time?
In August we discovered that I am paralyzed from my neck down through my toes by near rigor mortis-like dystonia, which I didn't know I had before going off meds. I was in shock last August when the doctor could find no detectable reflexes in either leg. I was unable to walk and thanks to cervical and truncal dystonia found it very difficult to breathe with a firm hold on my diaphragm, neck and throat. I wrote my doctor about my angst. My family and I look at each other with concern and say, "only 2 more times" - the eval and surgery day. I go off my meds courageously each time; this time I don't want to do it. It only takes about 6 hours to be fully engulfed by my PD but it takes 3 days for the meds to restore my ability to walk. Its like Cinderella and the pumpkin. I take my meds every day and like magic, I am ambulatory. I walk and do everything I've always done. Off my meds, the polar opposite. I thank Michael J Fox, researchers and doctors for the advances in PD, including this miraculous surgery that was created to halt my tremors, dystonias and dyskinesias. I have friends that have gone through it and all forget they have PD on most days. I cannot wait for my turn. I will be back to post the results after Friday.
Let's pray they schedule my surgery right away. My life is wonderful, happy, and full these days. I want to continue in full bore to enjoy it with the return of peace and stillness. If you do not have Parkinsons, I want you to take a few minutes to take a deep breath, hold it and listen to the silence. Just enjoy and thank God for your ability to be still. for it is a gift you don't realize you have. I will be there with you very soon.
LRRK2 Drug Trial Shares Promising Results,
Company to Begin Second Study
Posted by Maggie McGuire Kuhl,
December 21, 2017
Yesterday Denali Therapeutics announced positive results from its first-in-human LRRK2 inhibitor clinical trial. The experimental treatment is safe, and it lowers LRRK2 protein activity in humans' body cells. This is a meaningful milestone in the clinical development of a drug with potential to slow or stop Parkinson's progression (something no currently available treatment can do).
Denali also shared it is testing a second compound in a separate Phase I trial in control volunteers. Following completion of both trials, one of the two compounds will move into studies in people with Parkinson's carrying a LRRK2 mutation.
Read more below on this project and its treatment potential from our earlier report on Denali's initial public offering.
In a press release, the company announced its first trial showed greater than 90 percent inhibition of LRRK2 activity at peak drug levels. This is a critical early step in testing a drug -- does it do what you want it to do in the cell? Denali used two tests to measure inhibition, including one based on a finding from a Michael J. Fox Foundation-organized consortium linking LRRK2 to another protein.
"Mutations in LRRK2 are a major risk factor for Parkinson's disease. Targeting this degenogene represents a promising approach to develop disease-modifying medicines," said Ryan Watts, PhD, Denali CEO.
Read more on the findings and next steps.
December 8, 2017 -- San Francisco-based Denali Therapeutics has raised nearly $250 million in its initial public offering, marking the largest biotech IPO of the year. In announcing terms of the IPO -- a major milestone in the life cycle of any company as it first offers stock options publicly, garnering capital for growth and expansion -- Denali shared it is testing a LRRK2 inhibitor drug in a small trial of control volunteers.
Mutations in the LRRK2 gene are a cause of Parkinson's disease (accounting for one to two percent of all cases, but behind up to 40 percent in some populations) and are associated with higher activity of the LRRK2 protein. Scientists, therefore, are developing inhibitor drugs to offset that over-activation and protect cells. The Michael J. Fox Foundation has a robust roadmap strategy around LRRK2: funding many studies to understand more about the protein's connection to Parkinson's and how we may target it to slow or stop disease.
While we have not directly funded Denali, our investments have been critical to helping the company achieve its current promising LRRK2 program. Denali has used MJFF-supported research tools in its experiments, and an August 2016 Forbesarticle reported CEO Ryan Watts cited a unique MJFF-led consortium as influential in his decision to license and develop LRRK2 inhibitor compounds. The LRRK2 Safety Initiative tested compounds from Genentech, Merck and Pfizer for safety, finding lung tissue changes were reversible and not associated with functional problems.
"This is a textbook example of what we exist to do: persevere to overcome issues that would otherwise set PD drug development back by years," MJFF CEO Todd Sherer, PhD, told Forbes. "We're thrilled on behalf of everyone living with the disease that a highly-promising target continues to move forward."
Therapies like this -- targeting dysfunction associated with a genetic mutation -- are examples of precision medicine, prescribing treatments based on one's biology rather than clinical diagnosis. Earlier this year another Parkinson's trial began enrolling people with a mutation in the GBA1 gene, also associated with the disease.
A common question is if such therapies will work for people without those specific mutations. While we do not yet know, our Foundation is funding research to draw lines between implicated proteins and pathways, which may lead to wider use of treatments.
As its first human study continues, Denali gained approval to begin a trial of a different LRRK2 inhibitor compound in the Netherlands and also is developing therapies against Alzheimer's disease and amyotrophic lateral sclerosis (ALS). We will share more news on the company's Parkinson's trials as it is available.
MAYO UPDATE: Love my new doctor. Sharp, professional, great communicator, two decades of advanced work on PD, with his medical partner holds two patents related to a DBS system, and has 3000+ DBS surgeries under their belt. Their approach is conservative giving them only 4 negative outcomes in over 3000 DBS surgeries with only 1 geriatric death (fabulous odds!) In his opinion, surgery is in my future, but NOT TODAY. He asked if I would allow him to dial in an adjusted meds, eat & sleep routine first, which if done correctly should stall drilling holes in my head for another year. Uhhhh, let me think on that for a nanosecond!!!! Count me in Obi Won. I am happy to celebrate my PD's 9th anniversary in rebounded health and living fully. The move to Mayo is God sent in perfect timing. As I write this, I eye my bike sitting patiently in its stand. I have not been able to ride for a few months now. Tonight its whispering, "I'm ready when you are. Let's go for a ride!!!!!" I dust off my helmut sitting on the handlebars and reply in gratitude..... Amen.
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"Lisa Chalker is One Face of Early Onset Parkinson's Disease. Come along on her journey from symptoms to diagnosis; through treatments and therapies. There are highs and lows, miracles and heart notes, and the determination to never, ever, ever, ever give up on the power of HOPE."