Stem Cell Research: Alzheimer’s

Study Details

What are They Looking At?

• The primary goal of this trial is to determine if the nasal drop therapy is safe. As an early-stage study, it will carefully monitor for any side effects or negative reactions in patients.
• The researchers will also measure several other outcomes to see if the treatment shows any early signs of being effective for the different brain conditions being studied. This involves using specific, standard medical scales to track changes in symptoms for each disease, such as:
• Alzheimer’s Disease (using the ADAS-cog scale)
• Parkinson’s Disease (using the MDS-UPDRS scale)
• Multiple System Atrophy (using the UMSARS scale)
• Lewy Body Dementia (using the ADCS-CGIC scale)
• Frontotemporal Dementia (using the CDR+NACC FTLD scale)
• Amyotrophic Lateral Sclerosis (ALS) (using the ALSFRS-R scale)

Types of Cells Used

• The therapy uses a “cell-free” product called hUC-MSC-sEV-001, delivered as nasal drops.
• What it is: This treatment is not made of whole stem cells. Instead, it uses small extracellular vesicles that are naturally released by umbilical cord mesenchymal stem cells. Think of it like using just the stem cells’ helpful messages, delivered in a liquid drop.
• The Goal: The idea is that these vesicles, delivered through the nose, might reach the brain and provide therapeutic benefits for these neurological conditions.
• Cell Source: The vesicles are derived from allogeneic hUC-MSCs, meaning the original stem cells came from healthy, screened umbilical cord donors.
• Dosage: Unknown

Delivery Method

• The treatment will be administered as nasal drops.
• This is an open-label, single-arm study, meaning all participants will receive the active treatment (there is no placebo group for comparison in this early safety trial

What They’re Measuring

• Since this is an early Phase 1 study, the main focus is on safety.

Primary Goal (Effectiveness & Safety):

• Safety Monitoring: Researchers will track all side effects experienced by the patients throughout the year.
• Disease Progression: They will use specific, standard medical rating scales for each different neurodegenerative disease (like Alzheimer’s, Parkinson’s, ALS, etc.) to see if there are any positive changes in symptoms by the 6 or 12-month mark.

Other Outcomes:

• Researchers will also look at several general health indicators to get a broader picture of the treatment’s impact:
• Daily Function: Measuring changes in the ability to perform basic daily activities using the Barthel Index.
• Cognitive Function: Using the simple Mini-Mental State Exam (MMSE) to check for changes in thinking and memory.
• Quality of Life: Using the EQ-5D-5L questionnaire to see if the therapy improves the patients’ overall well-being.

Next Steps

• Follow-up Schedule
• This trial involves a one-year follow-up period after patients receive the nasal drop treatment. Safety will be monitored throughout this time. The researchers will check how well the treatment might be working at 6 months and 12 months after the therapy begins. (For ALS patients, some key measures are only checked up to 6 months).

What are They Looking At?

• The main goal is to see if the stem cell infusion can reduce behavioral problems associated with Alzheimer’s disease.
• Researchers also want to find out if the treatment might allow patients to lower the dose or reduce the number of antipsychotic medications they need to take.
• Although it’s not the primary focus, they will also be monitoring the safety of the infusion.

Type of Cells Used: Human Mesenchymal Stem Cells (hMSCs)

• What they are: The study is using a general category of cells called human Mesenchymal Stem Cells. These are known for their potential healing and anti-inflammatory properties.
• The Goal: The idea is that these cells might help calm the inflammation or other processes in the brain that contribute to the behavioral issues seen in Alzheimer’s disease.
• Cell Source: We don’t know where these hMSCs come from or if they are from the patient or a donor.

Dosage

• Each participant receives a single infusion containing approximately 25 million Mesenchymal Cells.

Delivery Method

• The treatment is delivered as a one-time IV infusion.
• This is an open-label, single-group study. This means all 8 participants will receive the stem cell treatment. There is no placebo group for comparison in this pilot study.

• The researchers will track changes over a 12-week period after the infusion.

Primary Goal

• Behavioral Symptoms: The main measurement is the change in the score on the Neuropsychiatric Inventory. This is a standard questionnaire used to assess the severity of behavioral problems like agitation, delusions, and apathy in dementia patients. A lower score indicates improvement.

Other Outcomes

• Medication Use: They will track whether the dose or the total number of antipsychotic medications the patient is taking changes between the start and end of the 12-week study period.

Follow-up Schedule

• This is a short pilot study. Participants will be involved for a total of up to 12 weeks, during which the main effects of the single infusion will be measured.
• The study record doesn’t mention longer-term follow-up beyond this period.

What They’re Testing

• This study is testing whether stem cells taken from a person’s own fat tissue can help reduce brain inflammation and slow down memory loss.
• Participants will undergo a fat biopsy to collect stem cells.
• They’ll receive 4 IV infusions of their own stem cells over a 13-week period.
• Each infusion contains about 200 million cells in a saline solution.

Primary Outcomes

• Changes in brain inflammation, tracked using PET scans and biomarkers like TSPO (a signal of activated brain immune cells).
• Inflammatory markers in spinal fluid (CSF).

Secondary Outcomes

• Safety: number of side effects.
• Changes in memory and thinking using tests like MMSE and RBANS.
• Changes in Alzheimer’s-related proteins in spinal fluid (like Tau, Amyloid-β, and Nf-L).
• Brain metabolism changes via FDG-PET scans.
• Daily functioning, measured using the Lawton IADL scale.
• Immune markers in blood and spinal fluid.

Procedure

• The study is an open-label trial, which means both the patients and doctors know what treatment is being given.
• Follow up was done 12 months after the injection.

Cell Type & Source

• The study uses autologous adipose-derived stem cells, which means the cells are taken from the patient’s own fat tissue through a procedure called lipoaspirate.

Delivery Method

• The cells are injected directly into the brain’s ventricles (fluid-filled cavities).
• To do this, a soft plastic pouch called an Ommaya reservoir is surgically placed under the scalp. The reservoir allows doctors to bypass the blood-brain barrier and deliver the cells where they need to go.

Dosage

• The trial uses a “dose escalation” design, with three different doses:
• Low dose: 2 million cells
• Medium dose: 5 million cells
• High dose: 10 million cells

Culture Method

• After the cells are collected, they are grown and multiplied in a lab and also “Wnt-activated.” This is a specific process designed to enhance their effectiveness.

How the Cells Are Believed to Work

• The researchers believe the therapy works by stimulating the brain’s own ability to repair itself and by reducing inflammation.
• This regenerative approach may be more comprehensive than current treatments that only target specific proteins like amyloid plaques.
• The cells are not meant to turn into new brain cells.
• Instead, they are designed to send out helpful signals to improve the brain’s environment.
• The direct injection method helps these signals reach their target and maximize the cells’ activity.

Results So Far

• Follow-up duration: 12 to 72 weeks for safety, with secondary outcomes measured at 12 weeks.
• Primary Outcome: The primary goal was to confirm the safety of the therapy, which was achieved with a clean safety profile. No adverse events were observed that were directly attributable to the stem cell injection.

Key Findings

• The therapy showed promising early signs of efficacy, with most patients experiencing improvements in cognitive and biomarker scores.
• Researchers believe the cells worked by stimulating the brain’s own ability to repair itself and reducing inflammation, rather than turning into new brain cells.
• The treatment was found to be safe, with no major side effects directly related to the stem cell injection over 12–72 weeks.

Efficacy Data at 12 Weeks

• Cognitive Scores:
• ADAS-cog improved in 80% of evaluable participants. This is a widely used test to measure the severity of cognitive impairment in patients with Alzheimer’s disease.
• MMSE improved in 60% of evaluable participants. A test used to check for cognitive impairment and to track a person’s mental status over time.

• Biomarkers:
• p-Tau improved in 80% of evaluable participants.
• Lower levels of the p-Tau protein are significant because they suggest the therapy is effectively reducing the harmful protein buildup directly linked to the progression of Alzheimer’s disease.
• Amyloid PET centiloid scores decreased in 60%. Lower amyloid PET centiloid scores are a good thing because they indicate a reduction in the abnormal amyloid plaques in the brain, which are a key sign of Alzheimer’s disease.

What’s Happening Next

• The Phase 1 trial has now concluded with six participants.
• Regeneration BioMedical announced in a press release in August 2025 it has submitted the results to the FDA and is preparing to launch a multi-site, placebo-controlled Phase 2 trial in the United States.
• The team is also planning to explore this approach for other neurodegenerative diseases, including Parkinson’s disease, ALS, multiple sclerosis & chronic traumatic encephalopathy (CTE).

What They Tested

• The treatment is called Lomecel-B (laromestrocel). A type of stem cell therapy made from donor bone marrow.
• Participants were randomly placed into four groups:
• Group 1: Placebo (no stem cells), given 4 times
• Group 2: One infusion of 25 million stem cells, then 3 placebos
• Group 3: Four infusions of 25 million cells
• Group 4: Four infusions of 100 million cells
• All treatments were given through a standard IV drip, once a month for four months.

What They Measured

• Main Goal: Make sure the treatment was safe, looking for side effects or problems on brain scans.

• Other Goals:
• Track changes in memory and thinking, using tools like MMSE and ADAS-Cog.
• Measure brain shrinkage (especially in the hippocampus) using MRI.
• Look at inflammation in the brain through advanced imaging.
• See if cognitive improvements matched physical brain changes.

What They Found

• Safe: There were no serious side effects, and no brain issues like swelling or microbleeds on MRI.

• Cognitive improvement:
• 60–80% of patients improved on memory and thinking tests.

• Slowed brain shrinkage:
• Whole brain shrank 48% less compared to placebo.
• Hippocampus (a key memory area) shrank 62% less.

• Less brain inflammation was seen on imaging.
• Cognitive improvements matched physical improvements in the brain.

Next Steps

• They’re now waiting for top line results in the final quarter of 2026.
• This is one of the most advanced stem cell trials for Alzheimer’s to date.
• It shows that laromestrocel (Lomecel-B) is safe and may help slow brain degeneration and improve memory without the side effects seen in other treatments like antibody drugs.
• A larger Phase 3 trial may be next to confirm these results.
• While the treatment showed promising results overall, the study did not report whether higher doses led to better outcomes, so it’s still unclear if more cells provide more benefit.

Procedure

• Delivery Method: The treatment was given as nasal drops, administered using a spray device into alternating nostrils over about 10 minutes.
• Cell Type & Source: The study used exosomes derived from adipose (fat) mesenchymal stem cells. These were allogeneic, meaning the original stem cells came from healthy young adult donors.
• Dosage: The study tested three different doses, given twice a week for 12 weeks:
• Low Dose: 200 million exosome particles per dose.
• Medium Dose: 400 million exosome particles per dose.
• High Dose: 800 million exosome particles per dose.
• Cell Prep & Quality: The exosomes were produced in a strict, cGMP-compliant lab. They used a process involving precipitation and ultracentrifugation to collect the exosomes. Rigorous quality checks were done to confirm the exosomes’ size, shape, protein markers and purity before use.

Safety (Primary Endpoint)

• Excellent Safety: The treatment was considered very safe. No side effects or serious adverse events were reported during the entire 12-week treatment period. Standard lab tests and vital signs remained normal.

Effectiveness (Cognitive & Brain Changes)

• Medium Dose Showed Benefit: Only the medium-dose group showed consistent signs of cognitive improvement after 12 weeks.
• Scores on the ADAS-cog test (where lower is better) decreased by 2.33 points.
• Scores on the MoCA-B test (where higher is better) increased by 2.38 points.
• Lasting Effect: These cognitive improvements in the medium-dose group seemed to persist during the follow-up, with ADAS-cog scores continuing to improve until week 36.
• Brain Scans: While PET scans showed no significant overall reduction in amyloid or tau after one year, MRI scans suggested that brain shrinkage in the hippocampus might have been less pronounced in the medium-dose group.

How the Exosomes Worked

• The researchers believe the benefits came from the helpful molecules inside the exosomes. Their analysis showed the exosomes contained proteins and genetic material (microRNAs) known to support brain health by potentially:
• Promoting the growth of new nerve cells and blood vessels.
• Helping the brain form new connections.
• Reducing inflammation and possibly clearing amyloid.

What We Don’t Know (Limitations)

• Very Small Study: With only 3 patients in each dose group, it’s impossible to draw firm conclusions about effectiveness.
• No Placebo Group: Because everyone received the treatment (open-label design), we can’t be sure if the improvements seen were due to the exosomes or a placebo effect.
• Short Treatment: The 12-week treatment period might not be long enough to see major changes, especially in brain plaques.
• PET Scan Timing: The follow-up brain scans were done a year later, making it hard to see if there were short-term changes after the treatment ended.

Conclusion

• This study showed that using exosome nasal drops derived from fat stem cells is safe for patients with mild to moderate Alzheimer’s.
• The medium dose (400 million particles) showed promising early signs of improving cognitive function, with effects lasting for several months after treatment.
• These encouraging, though very preliminary, results support the need for larger, randomized, placebo-controlled trials to truly confirm if this could be an effective treatment for Alzheimer’s disease.

What Was the Treatment?

• The treatment involved injecting stem cells directly into the brain using a small device placed under the scalp (called an Ommaya reservoir).
• Each person got 3 injections total, one every 4 weeks.

Dosage

• Two dosage levels were tested:
• Low dose: 10 million cells per injection.
• High dose: 30 million cells per injection.

Safety

• Mostly, yes. But there were some short-term side effects:
• Everyone got a fever after the injection.
• Some people felt sick, had headaches, chills, or muscle aches.
• These symptoms lasted less than 2 days.
• No one had long-term problems & brain scans showed no serious issues.
• Bottom line: The treatment was generally safe, even though it caused brief fevers and discomfort.

Did It Help?

• This trial wasn’t designed to prove whether the treatment works. It was focused on safety. But the doctors still looked for early signs of improvement:
• Some Alzheimer’s related proteins (like tau and amyloid) went down right after the injection, but only for a short time.
• Memory test scores didn’t really improve.
• Brain scans looked mostly the same after a year.
• So while the stem cells may have had some short term effects, they didn’t lead to big improvements in memory or thinking, at least not in this small group.

Final Thoughts

• This was one of the first studies to test whether stem cells from umbilical cords can be safely injected into the brain of people with Alzheimer’s.

Here’s why it’s important:

• The approach was safe enough to keep testing.
• It showed that repeated brain injections are possible.
• It raised new questions, like whether higher or more frequent doses are needed to see real benefits.

So, What Happened to NeuroStem

• After the initial trial showed the treatment was safe, researchers followed patients for another 3 years to track long-term effects. But here’s the thing, no results have ever been published and there’s been no press release or update since that follow up study ended.
• Even more telling? The treatment is no longer listed on MEDIPOST’s website.
• That usually means one of two things:
• The results weren’t exciting enough to move forward, or
• The company quietly shifted focus to other therapies that showed more promise.
• It doesn’t necessarily mean Neurostem failed or caused harm, just that it likely didn’t work well enough to justify a larger, expensive trial. Instead of announcing that publicly, the company seems to have just let it fade away.
• So for now, Neurostem looks like a promising idea that didn’t quite pan out. At least not yet.

Effectiveness

• The review noted that the studies showed some improvements in biomarkers and clinical outcomes as a secondary finding. However, the researchers emphasized that the evidence for effectiveness is currently limited and based on studies with small sample sizes.

Mechanism of Action

• The review suggests that the stem cells work through several mechanisms to improve brain health, rather than just replacing cells.
• Reducing Inflammation: The cells are thought to work by reducing inflammation and oxidative stress in the brain.
• Supporting Cells: They may help form and maintain the brain’s neural networks by supporting existing brain cells and preventing the buildup of toxic proteins.
• Promoting Growth: The review also mentions that some studies show the cells’ potential to promote the growth of new brain cells (neurogenesis) and new connections (synaptogenesis).

Delivery Methods

• The studies used different ways to get the cells into the brain:
• Direct Brain Injections: Injections into specific brain regions, like the bilateral hippocampi and the right precuneus.
• Brain Cavity Injections: Injections directly into the brain’s fluid-filled cavities (intracerebroventricular injection).
• IV Infusion: Intravenous (IV) injection into the bloodstream.

Safety

• The therapies were found to be well-tolerated and safe across all five reviewed studies, with no significant safety concerns linked to the injections.

Common Side Effects

• The most common side effects were mild and short-lived, such as fever, headache, dizziness, nausea and surgical wound pain.

No Serious Events

• No serious events like tumor formation, cerebral hemorrhage, or hydrocephalus were reported in the long-term follow-up of these studies.

Researchers’ Conclusions

• The researchers concluded that cell-based therapies are a promising new therapeutic approach for Alzheimer’s disease because they are well-tolerated and appear to reduce disease progression.
• However, they strongly recommend that future research address the limitations they found, such as the small number of studies, small sample sizes, and a lack of well-designed, randomized controlled trials.