Allogeneic Bone Marrow–Derived Mesenchymal Stem Cell Safety in Idiopathic Parkinson's Disease

[Bolt_Upright]

Credit to Hidden and kevowpd !

Allogeneic Bone Marrow–Derived Mesenchymal Stem Cell Safety in Idiopathic Parkinson's Disease 2021 (full text) ncbi.nlm.nih.gov/pmc/articl...

"Background

Neuroinflammation plays a key role in PD pathogenesis, and allogeneic bone marrow–derived mesenchymal stem cells can be used as an immunomodulatory therapy.

Objective

The objective of this study was to prove the safety and tolerability of intravenous allogeneic bone marrow–derived mesenchymal stem cells in PD patients.

Methods

This was a 12‐month single‐center open‐label dose‐escalation phase 1 study of 20 subjects with mild/moderate PD assigned to a single intravenous infusion of 1 of 4 doses: 1, 3, 6, or 10 × 106 allogeneic bone marrow–derived mesenchymal stem cells/kg, evaluated 3, 12, 24, and 52 weeks postinfusion. Primary outcome safety measures included transfusion reaction, study‐related adverse events, and immunogenic responses. Secondary outcomes included impact on peripheral markers, PD progression, and changes in brain perfusion.

Results

There were no serious adverse reactions related to the infusion and no responses to donor‐specific human leukocyte antigens. Most common treatment‐emergent adverse events were dyskinesias (20%, n = 4) with 1 emergent and 3 exacerbations; and hypertension (20%, n = 4) with 3 transient episodes and 1 requiring medical intervention. One possibly related serious adverse event occurred in a patient with a 4‐year history of lymphocytosis who developed asymptomatic chronic lymphocytic leukemia. Peripheral inflammation markers appear to be reduced at 52 weeks in the highest dose including, tumor necrosis factor‐α (P < 0.05), chemokine (C‐C motif) ligand 22 (P < 0.05), whereas brain‐derived neurotrophic factor (P < 0.05) increased. The highest dose seems to have demonstrated the most significant effect at 52 weeks, reducing the OFF state UPDRS motor, −14.4 (P < 0.01), and total, −20.8 (P < 0.05), scores.

Conclusion

A single intravenous infusion of allogeneic bone marrow–derived mesenchymal stem cells at doses of 1, 3, 6, or 10 × 106 allogeneic bone marrow–derived mesenchymal stem cells/kg is safe, well tolerated, and not immunogenic in mild/moderate PD patients. "

[park_bear]

Impressive results. More:

"The potential therapeutic benefit of MSC therapy relies primarily on paracrine actions.39, 40 In this study, multiple peripheral markers were assessed to elucidate possible mechanisms of action. Our findings suggest a reduction in serum levels of TNF‐α and CCL22, with an increase in BDNF. There was an anti‐inflammatory effect that appeared to be more robust in the higher doses of groups C and D and may be related to a potential mechanism of action. High levels of TNF‐α and CCL2 and low levels of BDNF have been previously reported in PD patients.41, 42, 43

Moreover, high levels of TNF‐α correlate with worse motor scores.44 Previous animal studies have shown that intravenous MSCs can reduce TNF‐α in the substantia nigra45 and that systemic deficiency of TNF‐α is associated with improvement.46 Similar to our study, in 2 clinical trials using intravenous MSCs, CCL22 was significantly decreased at 12 months in autism spectrum disorder47 and at 2 weeks after infusion in an ALS study.48 We hypothesized that these peripheral changes could lead to an anti‐inflammatory microglial phenotype, which in turn could enhance neuronal survival and promote angiogenesis, consistent with the finding of increased basal ganglia perfusion."

I wonder if we will ever find a simpler way to get these effects without having to use stem cells.

[Boscoejean in reply to park_bear]

I would like it if the last line starting with "I wonder" would come true

[Bolt_Upright in reply to park_bear]

As far as stem cell treatments go, this one seems fairly simple and effective. I'm guessing you could even get cadaver stem cells. I vote we move this out of "experimental".

[Bolt_Upright in reply to park_bear]

Thanks for the details.

[Boscoejean]

was this research done in Houston?

[jimcaster in reply to Boscoejean]

Yes.

[jimcaster]

PrayN4aCure, may be able to shed more light on this.

healthunlocked.com/cure-par...

[jimcaster in reply to jimcaster]

PrayN4aCure

[jimcaster]

This research is supported by the Michael J Fox Foundation.

michaeljfox.org/researcher/...

[Sydney75]

Interesting, I have been following this type of therapy for chronic pain. However, they use your own bone marrow from a hip for regenerate damaged nerves.

pubmed.ncbi.nlm.nih.gov/315...

There is a medical practice in my state (FL) that does this regenerative treatment for pain, it is expensive.

[jimcaster]

I just corresponded with Vanessa K. Thyne, Clinical Research Coordinator at Houston’s Health University. Recruiting for a Phase III trial won't begin until 2024. The slow pace of trials is maddening.

[Bolt_Upright in reply to jimcaster]

Thanks Jim.

[Sydney75]

Two of my children are expecting babies, this make me think if they don't want to pay costs to store the cord blood, I should for my HWP