Objective: To evaluate the effect of ADS024, an oral single strain live biotherapeutic product (SS-LBP), on the pathophysiology of MPTP-induced Parkinson’s Disease (PD) phenotypes in mice and zebrafish.
Background: Gastrointestinal microbes have recently gained prominence in their ability to impact the brain via the gut-brain axis. PD is one of several diseases in which bacteria may play a role in disease progression or modification. ADS024, an oral single strain LBP of Bacillius velezensis, is being evaluated for the potential treatment of patients with PD.
Method: Mice were dosed intraperitoneally with MPTP (Day 0 to 3; 20 mg/kg/day; n=30) or sham treated (saline; n=10). Mice were also orally gavaged (Days -3 to 7; bid) with saline (n=10), ADS024 (5×108 colony forming units (CFU); n=10), or bacterial formulation buffer containing Trehalose (n=10) and sacrificed on Day 7. Striatum was harvested, frozen, and homogenized in 0.3M perchloric acid. Dopamine and DOPAC were measured by reverse phase HPLC-EDC. Data were analyzed using two-way repeated measures ANOVA with post hoc Fisher’s LSD multiple comparison test. Zebrafish larvae were dosed with MPTP (250 uM; 96 to 120 hours post fertilization) or sham treated (DMSO only; n =22) in water. ADS024 was dosed in water of MPTP exposed fish (4×106 CFU/ml; n=16). Movement was evaluated with an imaging system during 50 min of testing consisting of 10-min periods of alternating darkness/bright light. Data was analyzed by One-way ANOVA followed by a Dunnet test comparing against MPTP treatment.
Results: MPTP-treated mice had significant reduction of striatal dopamine and DOPAC content (54% and 45% of sham, respectively), while treatment with oral ADS024 significantly attenuated the loss resulting in levels of 68% of sham in both cases (p<0.05 for both). MPTP-treated Zebrafish larvae had significantly reduced total motor movement distance (24% of sham; p<0.001) which was attenuated by ADS024 (61% of sham; p<0.001).
Conclusion: Oral treatment with ADS024 improved dopamine and DOPAC striatal levels in an MPTP mouse model of PD and led to improved motor movement in an MPTP zebrafish model. Together, these results suggest that ADS024, an oral SS-LBP, has potential for positive impact on dopamine and associated motor movement for treatment in Parkinson’s Disease.
To cite this abstract in AMA style:L. Chesnel, S. Acton. ADS024 attenuates striatal dopamine loss and restores movement in animal models of Parkinson’s disease [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/ads024-attenuates-striatal-dopamine-loss-and-restores-movement-in-animal-models-of-parkinsons-disease/. Accessed December 7, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/ads024-attenuates-striatal-dopamine-loss-and-restores-movement-in-animal-models-of-parkinsons-disease/