Slowing Parkinson’s by Blocking a Key Protein

 Your competent? doctor needs to know about this because of your risk of Parkinsons post stroke. 

Parkinson’s Disease May Have Link to Stroke March 2017 

Slowing Parkinson’s by Blocking a Key Protein

Summary: Researchers identified a promising new target for slowing the progression of Parkinson’s disease (PD). The study demonstrates that a protein called GPNMB (glycoprotein nonmetastatic melanoma B) acts as a catalyst for the spread of toxic alpha-synuclein clumps between neurons.

By using monoclonal antibodies to block this protein, scientists were able to interrupt the cycle of damage in preclinical models, offering a potential path toward the first disease-modifying therapy for PD.

Key Research Findings

• The Alpha-Synuclein Driver: Parkinson’s progresses as abnormal clumps of alpha-synuclein move from affected neurons to healthy ones, leading to cell death and worsening symptoms like tremors.
• The Role of Microglia: The brain’s immune cells, microglia, are a major source of GPNMB. When neurons are injured, microglia increase GPNMB production; enzymes then release the protein, allowing it to move freely and accelerate the spread of pathology.
• A Self-Reinforcing Cycle: The study suggests PD is driven by a feedback loop: alpha-synuclein damages neurons, which triggers the release of GPNMB, which in turn speeds up the spread of alpha-synuclein to more neurons.
• Human Evidence: Analysis of 1,675 brains from the Penn Brain Bank showed that individuals with genetic variants for high GPNMB production had more extensive alpha-synuclein pathology.
• Specificity: Elevated GPNMB levels were specifically linked to Parkinson’s and were not associated with markers for other neurodegenerative conditions like Alzheimer’s disease.
  

Source: University of Pennsylvania

Monoclonal antibodies can block a key immune‑related protein that drives the spread of brain cell damage in Parkinson’s disease (PD). 

This protein, called glycoprotein nonmetastatic melanoma B (GPNMB), might be part of a promising strategy for developing a treatment that slows disease progression at its earliest stages, according to a new study published today in Neuron, from researchers at the Perelman School of Medicine at the University of Pennsylvania.  

Interruption of the self-reinforcing GPNMB cycle could potentially slow or stop the neurodegeneration that follows the spread of alpha-synuclein through the brain. Credit: Neuroscience News“Many patients with Parkinson’s disease are diagnosed in the early stages, when symptoms are relatively mild, but there is currently no treatment that slows the progression,” said lead author, Alice Chen‑Plotkin, MD, Parker Family Professor of Neurology.

“These early results are a promising step towards developing this type of treatment.” 

How Parkinson’s disease spreads through the brain

PD affects more than one million people in the United States, with roughly 90,000 new diagnoses each year. While the exact cause of the disease remains unclear, scientists have long known that PD spreads through the brain in stages. 

This progression is driven by abnormal clumps of a neuronal protein called alpha‑synuclein. These clumps accumulate inside affected neurons, contributing to their dysfunction and death, and are then released and taken up by nearby healthy neurons.

As this pathology moves through different brain regions, patients experience the worsening symptoms that characterize PD, like tremors and difficulty walking or swallowing. 

While there are a number of medications and therapies that can help improve the symptoms of PD—ranging from a drug called levodopa to deep-brain stimulation delivered through an implanted electrode—there is no existing treatment that slows the progression of PD.  

Identifying immune cells as an unexpected therapy  

In earlier work published in 2022, Chen‑Plotkin and colleagues identified GPNMB as a key molecule involved in the neuron‑to‑neuron spread of alpha‑synuclein pathology, making it a compelling therapeutic target. 

In this new study, the researchers discovered that microglia, the brain’s resident immune cells, are a major source of GPNMB related to Parkinson’s disease. When microglia are near injured or dying neurons, they produce increased amounts of GPNMB. Enzymes then separate the protein from the cell surface, releasing part of it to move freely between cells. 

In preclinical experiments using cultured neurons, Chen-Plotkin developed antibodies that block GPNMB prevented the spread of alpha‑synuclein pathology from cell to cell.

“These results suggest Parkinson’s disease may be driven by a self reinforcing cycle—alpha-synuclein accumulates in neurons, damaging the neurons. The injury to the neurons initiates the release of GPNMB, which accelerates the spread of alpha-synuclein, leading to further damage,” Chen‑Plotkin said.

“Interrupting this cycle would hopefully slow, or even stop, the spread of alpha-synuclein through the brain and the neurodegeneration that follows.”  

Charting a potential path toward disease modifying therapy 

To assess the relevance of these findings in people, the team analyzed tissue from 1,675 brains in the Penn Brain Bank. Individuals with genetic variants associated with higher GPNMB production showed more extensive alpha‑synuclein pathology, providing strong human evidence that the protein plays a central role in disease progression. What’s more, elevated levels of GPNMB were not associated with the markers of other neurodegenerative diseases like Alzheimer’s disease. 

“These results are promising for laboratory models and human brain tissue analysis, but we still have a lot of work to do before we can translate this therapy into humans,” said Chen-Plotkin. “That being said, these results are encouraging as we continue to work towards a novel treatment for PD.” Funding: This study was supported by the National Institutes of Health (R37 NS115139, P30 AG010124, U19 AG062418, P01 AG084497), SPARK‑NS, the Parker Family Chair, and the Lipman Family Fund. 

Key Questions Answered:

Q: Why is this different from current Parkinson’s medications?

A: Current treatments, like levodopa, only manage symptoms, they don’t stop the underlying brain damage. This antibody therapy aims to be “disease-modifying,” meaning it could actually slow or stop the physical spread of the disease through the brain.

Q: How do antibodies “block” the damage?

A: The monoclonal antibodies developed by the researchers bind to the GPNMB protein. By latching onto GPNMB, they prevent it from interacting with neurons and spreading the toxic alpha-synuclein “seeds” to healthy cells.

Q: Is this treatment available for patients now?

A: Not yet. While the results in laboratory models and human tissue analysis are highly encouraging, the researchers emphasize that more work is needed before this can be translated into human clinical trials.Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.

About this Parkinson’s disease research news

Author: Eric Horvath
Source: University of Pennsylvania
Contact: Eric Horvath – University of Pennsylvania
Image: The image is credited to Neuroscience NewsOriginal Research: Open access.

“Secreted GPNMB enhances uptake of fibrillar alpha-synuclein in a non-cell-autonomous process that can be blocked by anti-GPNMB antibodies” by Marc Carceles-Cordon, Eliza M. Brody, Masen L. Boucher, Michael D. Gallagher, Robert T. Skrinak, Travis L. Unger, Cooper K. Penner, Adama J. Berndt, Sromona Das, Katie Lam, Rudolf Jaenisch, Vivianna Van Deerlin, Edward B. Lee, Kurt Brunden, Kelvin C. Luk, and Alice S. Chen-Plotkin. Neuron
DOI:10.1016/j.neuron.2026.04.033

Tiny Peptide Shows Powerful Brain Healing After Traumatic Injury

 Ask your competent? doctor EXACTLY WHOM WILL BE TESTING THIS ON STROKE PATIENTS! Doesn't know how to do that? 

TOTAL FUCKING INCOMPETENCE!

This from 2022 would seem to suggest that glycoproteins also occur after stroke and might benefit from this drug also. But why listen to me; not medically trained, unlike your doctor who hasn't a fucking clue how to get you 100% recovered!

Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results January 2022

The latest here:

Tiny Peptide Shows Powerful Brain Healing After Traumatic Injury

Summary: A small peptide called CAQK, composed of just four amino acids, has shown remarkable neuroprotective effects in mouse and pig models of traumatic brain injury. When injected intravenously, CAQK travels directly to damaged brain tissue, where it binds to overexpressed proteins and reduces inflammation, cell death, and tissue damage.

Treated animals displayed improved memory and motor function without toxicity, suggesting strong potential for safe, non-invasive therapy. Researchers plan to seek FDA approval for human clinical trials, marking a major advance toward drug-based treatments for traumatic brain injury.

Key Facts:

• Targeted Repair: CAQK homes in on injured brain areas, reducing inflammation and cell death.
• Non-Invasive Therapy: Delivered intravenously, avoiding risky brain injections.
• Pre-Clinical Success: Improved recovery in mice and pigs without toxicity; human trials planned.

ource: CSIC

Advanced Chemistry of Catalonia (IQAC) of the Spanish National Research Council (CSIC), an institution under the Ministry of Science, Innovation and Universities, has discovered that a small compound—a peptide made up of four amino acids called CAQK—has a significant neuroprotective effect in mouse models of traumatic brain injury.

When administered intravenously shortly after injury in animal models (mice and pigs), CAQK specifically targets the damaged areas of the brain, attracted by a protein that is overexpressed in injured tissue following trauma.

CAQK accumulates in the region marked by this protein and is able to reduce inflammation, cell death, and damage to brain tissue. Moreover, in mice, it improved functional recovery without apparent toxicity.

The results, published in the journal EMBO Molecular Medicine, open new possibilities for treating injured areas of the brain.

The study was led by the company Aivocode (a spin-off of the Sanford Burnham Prebys Institute) in San Diego, California, in collaboration with the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) and the University of California, Davis.

Aivocode, founded by researchers Aman P. Mann, Sazid Hussain, and Erkki Ruoslahti (authors of the study), plans to soon seek authorization from the U.S. Food and Drug Administration (FDA) to begin Phase I clinical trials in humans.

Although no specific date has been set, the fact that CAQK is a short peptide—easy to produce and with good tissue penetration—makes it a strong candidate for drug development.

Traumatic Brain Injury

Traumatic brain injury (TBI) is brain damage typically caused by blows to the head, such as those resulting from traffic accidents, workplace incidents, or falls. It is estimated to affect around 200 people per 100,000 inhabitants each year.

Currently, treatment focuses on stabilizing the patient by reducing intracranial pressure and maintaining blood flow, but there are no approved drugs to halt brain damage or its secondary effects, such as inflammation or cell death. In addition, the therapies under investigation require direct injections into the brain, an invasive technique that can cause complications.

“The current interventions for treating acute brain injury aim to stabilize the patient by reducing intracranial pressure and maintaining blood flow, but there are no approved drugs to stop the damage and secondary effects of these injuries,” explains Dr. Pablo Scodeller, researcher at IQAC-CSIC and co-author of the study.

The Great Challenge of Neurology

Finding a non-invasive way to treat an injured brain is one of the major challenges in neurology. This study moves in that direction, building on previous work carried out by the researchers in 2016 and published in Nature Communications.

At that time, researcher Aman P. Mann, together with Pablo Scodeller, working in the laboratory of Dr. Ruoslahti (senior author of both studies) at Sanford Burnham Prebys, discovered a peptide—a small chain of amino acids, the building blocks of proteins—that specifically targeted injured areas of the brain in mice.

The peptide, named CAQK, was identified through a large-scale screening technique known as peptide-phage display, which allows the selection of molecules with affinity for specific tissues. In that earlier study, CAQK was used as a “vehicle” to deliver drugs directly to the damaged area.

However, in their new work, the researchers went a step further and demonstrated that the CAQK peptide itself has therapeutic effects.

To evaluate its therapeutic activity, the peptide was first administered intravenously shortly after a moderate or severe traumatic brain injury, and it was observed that the peptide accumulated in the injured brains of mice and pigs (the latter having brains more similar to humans than mice).

Furthermore, it was found that the peptide binds to special molecules called glycoproteins (proteins attached to sugars), which become more abundant after an injury and are part of the extracellular matrix—a supporting network that surrounds brain cells.

Treatment of mice with traumatic brain injury using this peptide resulted in a reduction in lesion size compared to control mice.

“We observed less cell death and lower expression of inflammatory markers in the injured area, indicating that CAQK alleviated neuroinflammation and its secondary effects. Behavioral and memory tests conducted after treatment also showed improvement in functional deficits, with no evident toxicity,” explains the study’s first author, Dr. Mann.

The study’s results demonstrate that the CAQK peptide can help repair the damaged area, highlighting its potential therapeutic applications following trauma.

“What’s exciting is that, in addition to proving highly effective, it’s a very simple compound—a short peptide that is easy to synthesize safely at large scale. Peptides with these characteristics show good tissue penetration and are non-immunogenic,” concludes Scodeller.

Key Questions Answered:

Q: What makes CAQK different from other brain injury treatments?

A: It can be administered intravenously and selectively targets injured brain tissue without invasive procedures.

Q: How does CAQK work?

A: The peptide binds to specific glycoproteins overexpressed after brain injury, reducing inflammation and protecting neurons.

Q: When could human trials begin for using CAQK to treat TBI?

A: Researchers plan to seek FDA authorization soon to start Phase I clinical testing.

About this neuropharmacology and TBI research news

Author: Pilar Quijada
Source: CSIC
Contact: Pilar Quijada – CSIC
Image: The image is credited to Neuroscience News

Original Research: Open access.
“A neuroprotective tetrapeptide for treatment of acute traumatic brain injury” 

Examination of Inter‐α Inhibitor Proteins in Permanent and Transient Focal Ischemia

 Will your competent? doctor ENSURE HUMAN TESTING GETS DONE? NO? So, you DON'T have a functioning stroke doctor, do you?

Examination of Inter‐α Inhibitor Proteins in Permanent and Transient Focal Ischemia

Takahiko Imai, PhD https://orcid.org/0000-0002-4422-2946, Andreia Lopes de Morais, PhD https://orcid.org/0000-0002-9351-2552, Tao Qin, BS, Yuichi Sasaki, MD, PhD, Yow‐Pin Lim, MD, PhD https://orcid.org/0000-0003-2697-7963, and Cenk Ayata, MD, PhD https://orcid.org/0000-0002-3644-6042 cayata@mgh.harvard.eduAuthor Info & Affiliations

Journal of the American Heart Association

New online

https://doi.org/10.1161/JAHA.124.036034

• Abstract
• Nonstandard Abbreviations and Acronyms
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Abstract

Background

Ischemic stroke is among the most prevalent diseases, with high death and morbidity. Numerous preclinical studies have reported efficacious interventions in rodent stroke models. However, reperfusion therapies remain the only clinically efficacious intervention to date. Rigor and reproducibility are now recognized as critical to bridge the preclinical–clinical disconnect. Inter‐α inhibitor proteins (IαIPs) are a family of structurally related glycoproteins with 2 major forms (inter‐α inhibitor and pre‐α inhibitor) in blood. Purified human plasma–derived IαIP has beneficial effects in sepsis and hypoxic–ischemic brain injury. More recently, IαIP improved focal ischemic stroke outcomes in mouse models. Here, we tested IαIP efficacy in both transient and permanent stroke mouse models, mimicking previously published study designs and protocols to seek reproducibility.

Methods and Results

Using healthy young male and female C57BL/6 mice, we induced transient or permanent endovascular filament middle cerebral artery occlusion (MCAO). Mice were divided into transient MCAO+vehicle, transient MCAO+IαIP (30 mg/kg), permanent MCAO+vehicle, and permanent MCAO+IαIP groups. IαIP or vehicle was administered intravenously at 6 and 18 hours after MCAO. End points were assessed at 2 days. Efficacy readouts included death, infarct volume and swelling, and 3 neurological tests. Contrary to the previous work, we did not find IαIP efficacious on any outcome readout in either transient MCAO or permanent MCAO.

Conclusions

Our data highlight the contribution of interlaboratory heterogeneity to study outcomes and suggest that interventions considered for clinical development should undergo rigorous testing in multiple single‐laboratory studies before entering a multicenter preclinical trial.

Experimental antiplatelet compound for acute stroke shows promise

Well, further research needed since this was done on healthy volunteers not persons who might need the drug.  This does make the assumption you know what those anticlotting therapies this may replace. So ask your doctor about this, it has only been out a month. No knowledge then your doctor is out-of-date, why are you seeing them? It also means your stroke hospital doesn't have a system to keep their stroke medical professionals up-to-date on stroke research. So the hospital is incompetent also, along with the president and the board of directors. We have to clean out a lot of dead wood in stroke.

Experimental antiplatelet compound for acute stroke shows promise

ScienceDaily | April 19, 2019

An experimental antiplatelet compound inhibited clot formation without increasing bleeding, a common and potentially dangerous side effect of current anticlotting therapies, according to new phase 1 research in Arteriosclerosis, Thrombosis and Vascular Biology, an American Heart Association journal.

The results of the industry-sponsored trial are based on a first-in-human study of the new compound called ACT017. The findings suggest that the drug may provide an effective and safer alternative to current antiplatelet therapies used in stroke patients, which can also increase the risk for dangerous bleeding in the brain.
"There is a clear need for a novel antiplatelet agent that resolves platelet aggregation and clot formation without raising the risk for bleeding. Such a therapy would considerably improve and expand our current therapeutic arsenal for the treatment of acute stroke," said Martine Jandrot-Perrus, MD, PhD, study senior author and scientist at France's National Institute of Health and Medical Research (INSERM) and a consultant for Acticor-Biotech, the company that developed the compound and funded the trial.
The drug is an antibody-based compound that inhibits blood platelet aggregation (or clumping) and clot formation by precisely targeting a protein called platelet glycoprotein VI (GPVI) found in platelets. This protein is critical for clot formation—a process marked by the clumping of platelets— but it does not play a role in regulating bleeding. This feature renders the GPVI protein an ideal target for a drug that inhibits the clumping of platelets but does so without increasing the risk for bleeding.

• See Also: Non-adherence to antiplatelet therapy after PCI ups risk of MACE in anemic patients

The trial involved 36 healthy volunteers (23 women and 13 men), ages 22 to 65, divided into six groups. In each group, six participants received intravenous infusions over 6 hours with various doses of the drug (ranging from 62.5 mg to 2,000 mg).
The drug was well-tolerated at all doses, without serious side effects. Notably, the compound did not appreciably prolong bleeding time, a marker indicating increased risk for dangerous bleeds. The study also showed that the extent and duration of the therapeutic effect was dose-dependent, reaching maximum effectiveness and duration at 2,000 mg. The most common side effects were mild to moderate headache and head discomfort, which resolved during the study.
"Our results are quite encouraging because they show the candidate compound is well-tolerated at doses even twice as high as the ones targeted for a future treatment and without any signs of bleeding," Jandrot-Perrus said. "Another encouraging finding is the fact that the drug's action on platelets is rapid, specific, and largely reversible within 24 hours."

To read more, click here.