Stem Cells for Alzheimer’s: Dr. Christopher Duma’s New Direct-to-Brain Approach

What if the answer to slowing Alzheimer’s was already inside our own bodies? Neurosurgeon Dr. Christopher Duma believes it might be, and he’s testing whether stem cells taken from a patient’s own fat tissue can be harnessed to protect the brain against neurodegeneration.

As medical director of Hoag Memorial Presbyterian Hospital’s Brain Tumor Program in Newport Beach, California, and president and founder of Regeneration Biomedical, Duma is leading a first-in-human clinical trial that delivers fat-derived stem cells directly into the brain’s ventricles. The goal: to determine whether these cells, taken from a patient’s own body, can safely and effectively treat neurodegenerative disorders that currently have no cure, like Alzheimer’s, ALS, and chronic traumatic encephalopathy. 

In this interview with Being Patient’s Mark Niu, Duma shares an inside look at the trial and its progress. He explains the approach, digs into the Phase 1 safety results — including encouraging early data on biomarkers and cognition — and shares plans for the upcoming Phase 2 trial, which will test this experimental treatment’s efficacy in a larger group of participants living with mild to moderate Alzheimer’s.

Being Patient: Dr. Duma, you pioneered injecting this technology, fat-derived cells, into the brain. Is it essentially taking your own stem cells and injecting it back into the brain?

Dr. Christopher Duma: Yes, this is the first of its kind in the world where we’re actually taking someone’s own stem cells from their fat in their abdomen, supercharging it, growing the cells, expanding them, supercharging them with a special supercharging agent. But what it does is it turns stem cells on and makes them very active. And that is what’s injected directly into the patient’s brain, [who] has Alzheimer’s disease. We’re hoping to use this for other diseases like ALS, Parkinson’s, MS, chronic traumatic encephalopathy. We’re starting with Alzheimer’s disease. 

The real issue is how do you deliver a drug into the brain that stays there and works? Other companies have tried intravenous [and] oral forms of drugs, and they just don’t make it into the brain because of that famous blood-brain barrier. We’re trying to thwart that little barrier and break through it by directly injecting the cells into the cavities of the brain.

Being Patient: How does that look? How do you inject it and with what sort of devices? What does the setup look like?

Duma: Our brains are hollow. It’s like a cantaloupe. If you cut the cantaloupe in half, it’s hollow in the middle. Our brains are the same. [The] ventricles are full of fluid. Imagine putting a little reservoir or a port that actually communicates with that. In a clinical setting, you could put a needle into that little reservoir and inject your own stem cells. They go down the tube into your ventricles, and then they percolate into your brain. 

It turns out that our brains are very permeable as we get older. We can deliver stem cells that get into the brain. We’ve done work with rats [and] pigs, and we’ve already proved this type of thing. Right now, we’re just finishing the Phase 1 trial in humans. The results have been very exciting.

Being Patient: What do the results show so far?

Duma: A Phase 1 trial, which is an FDA-cleared trial, is designed for safety. Since [they are] the first people to ever get this type of treatment, we want to make sure that it’s safe.

These patients are very brave, but they’ve all exhausted any other therapies. They have no other options, and they’re clinically deteriorating. We enroll them in the trial, and we put the reservoirs in, we take their cells, we expand them in our laboratory, and then we inject them into their brains. For Phase 1, it’s just a single injection, just to see if the patients do well. Not one of our patients even got a headache from the injection. They all did beautifully in terms of safety.

Any researcher and any research team that’s doing this type of work — we’re all interested in what’s called secondary effects. Secondary endpoints. Even though this is just a safety trial, did we see any patients get better? Did we see any improvements in the amyloid beta levels and the other levels of what we call phosphorylated tau? Tau protein is bad also. For the vast majority of the patients that we treated, their tau levels went down; their beta-amyloid levels decreased. For the majority of patients, their cognition actually improved, which is not the case with the other drugs that are out there now. They do well to get rid of beta-amyloid, but they don’t really have a great effect on cognition.

“For the vast majority of the patients
that we treated, their tau levels went
down; their beta-amyloid levels decreased.
For the majority of patients, their cognition
actually improved, which is not the case
with the other drugs that are out there now.”

Being Patient: You say cognition improves — by what measurement and how much?

Duma: We do have cognitive testing. We use various tests for cognition. One is called the mini-mental status exam (MMSC). Another is called the Alzheimer’s disease assessment scale of cognitive scoring (ADAS-Cog). Those are the gold standard for cognitive testing. You can see what their baseline is and whether they’re getting worse or better.

Being Patient: Is there a measurement by how much? Did it vary quite a bit?

Duma: If they improve by even the smallest amount, that’s a first in the field of medicine. So we were very excited that the majority of our patients improved. An improvement from scores that might be in the 70s — higher scores are worse — and you get them down into the 30s. That’s a significant difference. We were seeing that, but remember my disclaimer is this is not a Phase 2 trial. These are secondary endpoints in our Phase 1 trial that give us hope to move to a Phase 2.

“If they improve by even the smallest amount,
that’s a first in the field of medicine.
So we were very excited that the
majority of our patients improved.”

Being Patient: What type of patients did you test this on? Is there a certain group or stage that you went with?

Duma: There are seven stages of Alzheimer’s disease. We only use stages four and five. So mild to moderate Alzheimer’s disease was included in our trial. And those would be the same level of severity used in our Phase 2 trial.

Being Patient: Was there a certain age group that you targeted, or was it a variety of ages?

Duma: In Phase 1, we used 45- to 80-year-olds. In Phase 2, we’re going up to 85.

Being Patient: Will Phase 2 expand to a wider pool? Tell us about Phase 2.

Duma: Last Friday, we were cleared by the FDA to go to Phase 2. We presented our data to them about a month and a half ago, they reviewed it, and they allowed us to move to Phase 2. 

Phase 2 enrollment is beginning very shortly, probably within the next couple of weeks. Phase 2 is an efficacy trial. So we’re seeing, does this really work? OK, we had a clue in Phase 1 that it was working. But it is Phase 2 that will tell us whether it’s working statistically. 

In Phase 1, we have only nine patients. In Phase 2, we’re going to have 115 patients, and 115 patients spread around the United States. So we’re going to have five sites — [in] Florida, Northern California, Southern California — and that will be a multi-institution trial. And so that gives us a much broader idea as to whether this really works or not.

Being Patient: Are you targeting a specific type of Alzheimer’s? Who are the best candidates for this particular testing?

Duma: We’re targeting all forms of Alzheimer’s disease. We are excluding Pick’s disease, a disease related to Parkinson’s disease. So there is an inclusion and exclusion criteria for our trial, and the neurologists who refer and our principal investigators make those decisions whether they’re appropriate for the trial.

Being Patient: How does it work? Whoever’s a part of the trial, do they have to come back for regular treatment? 

Duma: Yes, as you might imagine, we do follow-up exams, follow-up MRIs, follow-up PET scans. This is all paid for by the company, Regeneration Biomedical, that’s sponsoring the trial. There is zero out-of-pocket expense for the patients, which is wonderful. Because it is an FDA trial, they have to be actively followed up with various scans and even clinical exams. 

Every three months they have to come back for an examination. Every month and a half, they might get some more blood tests done, spinal fluid drawn, that type of thing. We have a full regimen as to exactly when they would be coming back. Phase 1 was a single injection. Phase 2 is an injection every two months. So they would get the cells injected into the brain every two months in a clinical setting.

Being Patient: Where can people go to find more info on Phase 2?

Duma: regenerationbiomedical.com You go to the clinical trial section and you’ll see the ongoing trials. 

Being Patient: What milestones would convince you that stem cell therapy is sort of ready for wider clinical use?

Duma: I think the Phase 2 trial will tell it all. We have some very, very promising clues from Phase 1. So much so that I wouldn’t go to Phase 2 if we didn’t have these clues — if we had bad side effects or people were getting sick from the injections, or it didn’t do anything at all to any of the biomarkers. 

We looked at spinal fluid biomarkers — spinal fluid CSF levels of beta-amyloid and phosphorylated tau. The majority of patients all responded in the positive direction. Those are the suspicions. Now with Phase 2, we will know whether this works or not, and then it will move on from there. I would hope that I’ve opened the door for more research of injecting things directly into the brain. 

Being Patient: I just wanted to leave you with any final words about the future of treatment and whether you believe that stem cells will play a greater role.

Duma: I’m not going to say, ‘100 percent confident.’ There’s no 100 percent in my field, but I am 95 percent confident that we will be using stem cells specifically for these neurodegenerative diseases, which we’ve had nothing for, forever. So it is a new prospect. I can’t wait to see the results of Phase 2. And as I said, we just need funding for that to move forward. So the sky’s the limit when it comes to stem cells.