Let’s start with some (ahem) light reading about LRRK2 and GBA gene mutations in PD to set the stage for further comparison as to treatment options being studied that target them, and that may also work for people with PD without either of those mutations.
Targeting LRRK2 we have DNL151 (which may also help those without that mutation):
DNL151 is being moved into late stage trials next year based on trial findings to-date as follows:
“Results to date in DNL151 also show a target engagement of over 50%, and up to a 50% reduction of the lysosomal marker BMP (22:6-bis-monoacylglycero-phosphate) in urine samples, with this drop dependent on the DNL151 dose given. These data indicated that the study’s pharmacological goals were being met.”
To me DNL151 results sound promising, but I for one would like a little more clarity on how its goals translate into metrics used to snapshot PD cognitive and motor progression. If that is available, I would really appreciate someone posting it in reply.
Targeting the GBA gene we have Ambroxol, on which a trial was just completed with the following statements:
“Mean (SD) scores on part 3 of the Movement Disorders Society Unified Parkinson Disease Rating Scale decreased (ie, improved) by 6.8 (7.1) points (95% CI, –10.4 to –3.1; P = .001). These changes were observed in patients with and without GBA1 mutations.”
“we confirm that ambroxol has potential as a drug to target the glucocerebrosidase (GBA) pathway in PD and increase GCase activity in the brain. These findings concur with cell and animal modeling, which indicate that ambroxol modulates α-synuclein levels. We believe ambroxol therapy has promise for further investigation as a drug to improve outcomes, particularly in patients who have PD with a GBA1 mutation and potentially in those without a GBA1 mutation.”
With a significant trial underway ending next year - Ambroxol as a Treatment for Parkinson’s Disease Dementia:
As some of you know, I am currently taking Ambroxol for my PD, and have posted here about its positive impact on my progression which I believe is continuing at the 7 month+ mark, as I have noted fewer daily freeze episodes, and in fact have discontinued taking Ropinirole (Requip) without much movement change. Hopefully DNL151 if/when available will bring even more to our battle against PD, but until then I have something now that is working for me. I remain very hopeful that will continue, at the very least until something better comes along!