Hi, Dr. Ali. I would love to contribute to the project if you are still looking for collaborators! This perfectly aligns with my interests. Please let me know. Thank you!
My email is martinez120@usf.edu.
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Hi all,
We will have our next PD meeting on September 8th. There will be no meeting this Monday.
As we organize the new Brain AWG, we plan to consolidate into one joint meeting, with alternate updates focused on PD or ADBR. This may also involve a new meeting time—we are still working out the logistics. Please don’t forget to fill out your availability using the When2Meet form that Windy shared earlier via the ADBR reminder email: https://www.when2meet.com/?31805722-HOkp3
Thank you all for your continued commitment and contributions. I’m looking forward to more exciting analyses and productive discussions ahead!
Best,
Nilufar
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Hello. I am particularly interested in this research, I have some experience in degenerative diseases such as Parkinson’s and Alzheimer’s. I would really like to participate!
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Proposal to NASA: Investigating the Use of IV Lecanemab in Rats in Microgravity to Remove Amyloid Beta Plaque with and without Ultrasound to Open the Blood-Brain Barrier and its implications for Astronauts on long duration missions to Mars.
By David Barckhoff University of Pittsburgh
This proposal outlines a research study to investigate the efficacy of intravenous (IV) lecanemab in reducing amyloid-beta (Aβ) plaque in rats exposed to microgravity, both with and without focused ultrasound (FUS) to transiently open the blood-brain barrier (BBB). The study aims to assess the implications of these findings for astronauts undertaking long-duration missions to Mars, where microgravity exposure and potential neurodegenerative risks are significant concerns.
Background and Rationale
Long-duration space missions, such as those to Mars, expose astronauts to unique physiological stressors, including microgravity, radiation, and altered circadian rhythms. Emerging research suggests that prolonged exposure to microgravity may contribute to neurocognitive deficits and potentially accelerate neurodegenerative processes.[1] While the exact mechanisms are still being elucidated, changes in cerebral blood flow, intracranial pressure, and oxidative stress in microgravity environments are hypothesized to play a role in brain health.[2]
Amyloid-beta (Aβ) plaque accumulation in the brain is a hallmark pathology of Alzheimer’s disease (AD) and is associated with cognitive decline.[3] Recent evidence indicates that neuroinflammation and impaired waste clearance mechanisms, which can be exacerbated by stress and environmental factors, may contribute to Aβ pathology.[4] Given the unique stressors of spaceflight, it is plausible that astronauts could be at an increased risk for accelerated Aβ accumulation or impaired clearance.
Welcome to this research. I have been studying these diseases for over 2 years now. This research also encompasses it’s affects on Astronauts, sports related concussions & TBI in military combat Veterans.
IV dopamine-loaded nanoparticles for dopamine & Parkinson’s treatment
By David Barckhoff University of Pittsburgh
The use of intravenous (IV) dopamine-loaded nanoparticles combined with ultrasound to facilitate crossing the blood-brain barrier (BBB) is a promising approach for improving therapeutic outcomes in Parkinson’s disease (PD). Here’s a concise analysis based on available evidence:
Background
Parkinson’s disease is characterized by the loss of dopaminergic neurons in the substantia nigra, leading to dopamine deficiency in the brain. The BBB, a highly selective barrier, restricts the passage of most therapeutic agents, including dopamine, into the central nervous system (CNS). Traditional treatments like levodopa (L-DOPA) can cross the BBB but often require high doses, leading to side effects such as dyskinesias. Nanoparticles loaded with dopamine and techniques like focused ultrasound (FUS) have been explored to enhance targeted drug delivery to the brain while minimizing systemic side effects.
Dopamine-Loaded Nanoparticles
Dopamine-loaded nanoparticles, such as those made from poly(lactic-co-glycolic acid) (PLGA) or albumin/PLGA, have shown potential in preclinical studies:
- BBB Crossing: Studies in animal models (e.g., 6-OHDA-induced PD rats and mice) demonstrate that dopamine-loaded nanoparticles can cross the BBB, likely via transcellular routes like lipid-mediated diffusion or receptor-mediated transcytosis (e.g., through albumin-binding proteins like gp60). These nanoparticles release dopamine slowly, reducing clearance, autoxidation, and quinone adduct formation, which improves safety and efficacy compared to bulk dopamine or L-DOPA.
- Therapeutic Effects: In a 6-OHDA mouse model, albumin/PLGA nanoparticles loaded with dopamine (ALNP-DA) at a dose of 20 mg/animal (equivalent to 140 µg dopamine) restored motor coordination, balance, and sensorimotor performance to non-lesioned levels, outperforming L-DOPA-treated groups. Similarly, in rats, dopamine-loaded PLGA nanoparticles reversed neurobehavioral deficits with less dopamine required compared to traditional treatments.
Role of Focused Ultrasound (FUS)
Focused ultrasound, particularly when combined with microbubbles, can transiently and reversibly open the BBB, enhancing drug delivery:
- Mechanism: FUS with microbubbles causes mechanical disruption of tight junctions and induces active transport processes, allowing molecules as large as 100 nm to cross the BBB. The barrier typically restores within 4–6 hours, minimizing long-term risks.
- Preclinical Evidence: In PD models, FUS has been used to deliver therapeutic agents, including nanoparticles, to specific brain regions like the striatum or substantia nigra. For example, FUS-mediated delivery of glial cell-line derived neurotrophic factor (GDNF)-loaded brain-penetrating nanoparticles in a 6-OHDA rat model restored dopamine levels, dopaminergic neuron density, and motor function without toxicity.
- Clinical Feasibility: Phase I clinical trials have demonstrated the safety and feasibility of FUS-mediated BBB opening in PD patients with dementia (PDD), targeting regions like the parieto-occipito-temporal cortex. While these trials focused on other agents (e.g., amyloid-beta antibodies), they confirm that FUS is well-tolerated and can achieve localized BBB disruption.
Combining Dopamine Nanoparticles with Ultrasound
While no studies have directly combined IV dopamine-loaded nanoparticles with FUS in PD patients, the synergy of these approaches is highly plausible:
- Enhanced Delivery: FUS could increase the permeability of the BBB, allowing more dopamine-loaded nanoparticles to reach the nigrostriatal pathway. This could reduce the required dose, further minimizing systemic side effects like those seen with high-dose L-DOPA (e.g., dyskinesias).
- Targeted Action: FUS offers precise spatial control, enabling targeted delivery to affected brain regions (e.g., substantia nigra or striatum), which could enhance dopamine replenishment and improve motor symptoms more effectively than systemic administration alone.
- Preclinical Support: Studies combining FUS with other nanoparticles (e.g., GDNF-loaded or α-synuclein-targeted) show improved therapeutic outcomes in PD models, suggesting that dopamine-loaded nanoparticles could similarly benefit. For instance, FUS-enhanced delivery of gene vectors or nanoparticles has restored dopaminergic function in preclinical models.
Challenges and Considerations
- Clinical Translation: While preclinical studies are promising, no clinical trials have yet tested dopamine-loaded nanoparticles with FUS in PD patients. Safety, optimal dosing, and long-term effects need further investigation.
- Nanoparticle Design: The size, charge, and surface modifications of nanoparticles (e.g., PEGylation or targeting ligands like transferrin) are critical for BBB penetration and brain distribution. FUS may enhance delivery but requires nanoparticles to be stable and biocompatible.
- FUS Parameters: The safety of FUS depends on parameters like intensity and duration. Low-intensity FUS (LIFU) has been safe in non-human primates and PD patients, but high-intensity FUS could cause tissue damage.
-Disease Heterogeneity: PD’s variable progression and pathology (e.g., α-synuclein aggregation) may affect treatment efficacy. Biomarkers like dopamine transporter (DAT) imaging could help stratify patients and monitor outcomes.
Conclusion
IV dopamine-loaded nanoparticles, when combined with FUS, have the potential to improve therapeutic responses in PD by enhancing BBB crossing and targeting dopamine delivery to affected brain regions. Preclinical studies show that dopamine nanoparticles alone can restore motor function with fewer side effects than L-DOPA, and FUS has proven effective in delivering other therapeutics across the BBB in both animal models and early human trials. Combining these approaches could lead to more efficient, targeted, and lower-dose therapies, reducing side effects like dyskinesias. However, clinical trials are needed to validate this approach in PD patients, focusing on safety, efficacy, and optimal protocols.
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Hi Dr. Ali, I just recently joined AWG and am interested with the research aim to decipher pathways of PD. I would like to contribute into current ongoing work. Please let me know if this subgroup is still accepting folks, thank you!
My email is chiawaikit96@gmail.com
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Hi, welcome to the group! Please add your details in the member’s list- see you at the next meeting!
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Hello, I am interested in joining a group project
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Im interested 
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