Stem Cell Therapy for Neurological Disorders with Dr. Luis Martinez

Dr. Martínez specializes in regenerative medicine, optimal aging, and cell therapy. He earned his medical degree at The Ponce School of Medicine and completed his residency training at the University of Pennsylvania. He is board certified in Clinical Lipidology. Dr. Martinez also holds a Masters of Public Health with a concentration in Epidemiology. He is Co-Founder of the Clinical Peptide Society, a US based professional organization aimed at educating physicians and advancing the use of peptide therapeutics. Along with other colleagues, Dr. Martinez developed the world’s first Peptide Certification Program. Additionally, he trains physicians in other aspects of Regenerative and Age Management Medicine through his physician training portal Elite Group MD.

Transcript

Liz Sutherland (LS): Hi, I'm Dr. Liz Sutherland, Editor-in-Chief of the Journal of Restorative Medicine, a publication of the Association for the Advancement of Restorative Medicine. Today, it's my pleasure to interview Dr. Luis Martinez on the topic of stem-cell therapy. Dr. Martinez could you begin by explaining what stem-cell therapy is?

Luis Martinez (LM): Certainly, and thank you for having me. Stem-cell therapies involve utilizing what we know are stem cells, which are cells that are not differentiated and are capable of either continuously multiplying and keeping a stem cell pool or differentiating into other specific types of cells. Stem-cell therapy usually involves either a patient’s own stem cells, which are considered autologous stem-cell therapies or donor derived stem cells, which are considered allogeneic stem-cell therapies.

LS: When the stem-cell therapies are donor derived is there any risk of the cells containing abnormalities due to say environmental toxins or simply from errors during cell replication?

LM: That's a good question. There's always potential risks involved. However, as technology has progressed quite a bit we have very high standards of quality control for the types of cells that are grown and administered. I'd say almost all the time before a patient receives allogeneic stem-cell therapies, they have been properly evaluated and undergone screening before the patient is ready to receive them. The labs where these stem-cell therapies are grown and prepared go through all the types of quality control, infectious disease processes, looking at cell morphology, looking at everything to ensure that the final cellular product is adequate and can be given therapeutically in a clinical environment.

LS: What about immune system rejection of allogeneic stem cells in the recipient?

LM: Correct. Well, what we've seen is as you purify and use specifically certain cell populations such as purified mesenchymal stem cells, the risk for immune reaction goes down a lot. Now, traditionally when patients receive for example, bone marrow transplants, which are populations of diverse cells, within that transplant the possibility of reaction goes up and there needs to be even more intense criteria and evaluation processes for matching purposes, HLA matching and such. Now again, when we do very purified types of infusions such as in mesenchymal stem cell administrations the adverse reactions related to them go down dramatically.

LS: Thank you. What kinds of health conditions do you treat in your practice using stem-cell therapy?

LM: First of all, we have multiple practices. I have multiple practices in Puerto Rico and Florida which are within FDA territory. And then I also consult and travel and treat patients internationally. So really depends where we are obviously. Within the FDA-regulated spaces we limit stem-cell therapies to patient’s own autologous therapies. Internationally we have centers in Latin America, South America, Chile, and Costa Rica to be specific, we're able to use allogeneic stem-cell therapies. We've been focusing mostly on a couple of different routes: neurological treatments; and immune modulation and cancer. And then we're also doing a lot of systemic treatments targeting frailty and aging which is a really exciting field right now.

LS: So, both we could say pathological conditions and also the effects of what we might consider normal aging?

LM: Yes, which as time progresses, I think the general consensus is sort of switching slowly but surely into considering aging more of a disease state than just a normal gradual decline. As such, again we're focusing on that. We've seen already studies, there's a couple of biotech companies right now looking at the administration of mesenchymal stem cells systemically to address aging. There's been some studies already in the US -- phase I and phase II clinical trials with mesenchymal stem cells with good results. We know the science really supports this and I think the interventions will continue to grow.

LS: When many people think about stem-cell therapy, they think about growing new nerves or growing new cells. But it sounds like the effects of stem-cell therapy include a wide array of beneficial effects. Could you speak to some of those effects? If it's easier for you, use the example of particular patients that you've treated, or you can keep it abstract.

LM: Gladly. There's a couple of, as you mentioned, possibly misconceptions about stem-cell therapy or expectations as to what we will achieve. It’s not always for regeneration or repair. Sometimes we look at really affecting disease states and progress. For example, in cases such as Multiple Sclerosis where we know there's an ongoing autoimmune attack on myelin sheaths and on the central nervous system, what we're trying to do first of all with stem-cell therapies is shut down that immune attack because these stem cells have immunomodulating properties.

We can see, depending on the patient and disease state a). stopping progression and then b). Looking at repair regeneration. We've had some cases where we're able to stop MS progression. And then with subsequent treatments, we've seen improvements even on imaging of certain areas that have been affected because of the disease. So certainly I think it can be considered maybe a two-step approach in terms of what we're trying to do with stem-cell therapy. It’s the same when we address for example, joints, arthritis, cartilage degeneration, tendons, ligaments when we inject into these places. There's plenty of evidence now that we can impact and we can help the repair process.

LS: Does it seem to you that stem-cell therapy could address the root cause of some of these neurodegenerative, neuro-inflammatory conditions?

LM: Yes. I mean it definitely addresses I'd say root cause or one of the major aspects of the disease. Now sometimes these autoimmune diseases, even the CNS diseases, don't actually start in the CNS. They start because of different aspects, toxicity, leaky gut, different situations that will predispose the body towards autoimmunity. Sometimes depending on the disease we're targeting the root cause. In other situations, we're actually just focusing on a more physiological and more potent regulation of the disease. Because as you know, sometimes with these autoimmune conditions we're looking at, traditional medicine will prescribe steroid therapies chronically. And then there'll be next generation biologics, which comes with adverse events, side effects which can be serious. So through stem-cell therapies the idea is to help repair but also help modulate in a more physiological safe manner.

LS: Given that stem cells work through several mechanisms does that mean that you don't necessarily have to administer the stem cells to the target tissue, but you're aiming for a kind of overall systemic anti-inflammatory impact?

LM: Correct, and that's a wonderful point. We usually try to do both. When we have a certain condition, we'll try to address local tissue damage. But I also believe that systemic administration is always of benefit. And this goes back to our normal human physiology. If you look at when you have some sort of damage, the acute repair response from the body includes increased liberation of stem cells from the bone marrow space into circulation. So again, I think that systemic administration often mimics the normal repair process, which is impaired and affected by aging, chronic diseases, and inflammation.

LS: I can see where if you’re using stem-cell therapy in say an acute and evolving kind of situation like an acute stroke versus say Parkinson's disease, or another chronic degenerative condition, that the timing of the therapy would need to be taken into consideration. Is there an optimal timing for treatment?

LM: Based on my experience, I believe that the sooner we treat the better. I think it makes a lot of sense because of a). The additional damage that can occur with time with an untreated condition as you mentioned, Parkinson's, substantia nigra neurons continue to be affected, die-off, and deteriorate. The more you wait, the more damage you have to deal with, and the harder repair is. So, I believe that timing is always of the essence, and the sooner you can treat these patients the better.

LS: I understand there are several different modes of stem-cell therapy administration. Does the mode of delivery and the type of stem cell that you're going to use depend on the condition that is being treated?

LM: Yes. Mode of delivery and type of stem cell definitely will affect and will be dependent on the condition being treated. Of course, if we go back to some really straight out and straight forward conditions such as musculoskeletal pathologies then you really want to go into the space where it's affected: knees, joints, tendons, ligaments. You want to try to inject directly into the space affected because that's usually what will produce the best outcomes. Now when you're dealing with systemic conditions, autoimmune conditions, inflammatory condition, it can be more challenging because say for example, you can have autoimmune arthritis or lupus, and you can have distal organ damage. So usually you want to treat systemically and if possible, you can also treat specifically into certain organs. And the type of stem cell definitely has a lot to do with that. For example, in offshore or in Latin America, for the neuro conditions, we can actually culture mesenchymal stem cell that become pre-neural precursors. So, they are already committed to that neural lineage and we've seen better results with those than with just general stem cells.

LS: I see. So, in terms of administration, I was also thinking about the route being intravenous or intra-arterial. Do you use several different modes of administration?

LM: We do a lot of intravenous, and I think the intravenous route makes a lot of sense. There's been a lot of concern from critics regarding lung entrapment for intravenous therapies. But based on what we know and on studies, the lung entrapment process usually is temporary. And afterwards the cells eventually are released, and there's quite a bit of evidence of distal activity of the cells once they are released from the lungs. And so, we know they work, so intravenous is definitely a route we use. And again, intra-arterial we have used that route. We have, in combination with other colleagues for example, we've gone into heart treatments and other conditions where perhaps that intra-arterial route can help in combination with other systemic administrations.

LS: Do patients who are going to receive stem-cell therapy need to do any special preparations in advance?

LM: Yes, we usually do specific protocols prior to giving or administering these therapies. For example, we try to minimize systemic inflammation. We put patients on nutritional guiding, we do a type of time-restricted eating, intermittent fasting, fasting mimicking because we really want to optimize the body. And that's another very important point, when the stem cells reach their environments, there have to be favorable environments so they can respond better, and so that repair can be achieved. So yes, we have protocols that we call patient preconditioning prior to receiving the therapies, and those help.

LS: Would they be initiated about a month before?

LM: At least a month. We'll usually do between one and three months before the treatment. We'll have them on those protocols, diet, certain nutraceuticals, peptides and such to help with this.

LS: I'm sure you have many outstanding clinical case studies to share, but I'm wondering if you might pick one or two of them to tell us about?

LM: Definitely. There's a lot of them as you said. One of them in neuro, actually two, we had a patient post-stroke. Actually, the patient was already nine, ten months post-stroke, on rehab, and completely could not move his right side. We did administer multiple rounds of stem-cell therapies for this patient. We actually did a combination of intra-nasal, which is another route that we can do, intranasal and intravenous approaches. This patient regained almost completely normal functioning. And this was a patient who had been post-stroke, under a therapy, rehab, and his prognosis for regaining that level of functioning was not good. After the stem cell treatments, he responded extremely well. So that's definitely a case there which had really good results. We've also had really good results with orthopedic cases, patients with advanced arthritis, degenerative arthritis, significant loss of cartilage, that have had amazing results: tendon/ligament improvement and repair seen on imaging. A lot of autoimmune cases where systemic inflammation has been dramatically improved. Yes, a lot of cases do come to mind.

LS: The post-stroke patient, how long after their initial stroke did you administer stem-cell therapy?

LM: He visited us about nine months post-stroke.

LS: Wow, that's amazing!

LM: It is amazing. It was quite a bit of time afterwards. As you know, there's really a short window usually for the repair process and all that to really kick in. We treated him, and we weren't expecting such a dramatic result as we observed.

LS: I'd like to switch gears a little bit now if that's okay with you and ask you a couple of questions about neuropeptides. Do you sometimes combine neuropeptide and stem-cell therapy with your patients?

LM: Yes, totally. I'd say that's a very important point. I'd say that not sometimes but most of the time. What we've seen with peptides are amazing benefits. I love to integrate peptides into most of my treatments right now, including stem cell therapies, and neuropeptides have been wonderful. We've had really good results with peptide therapies in the neuro space and in other conditions. Yes, we do a lot of integration. And oftentimes we'll have patients continue peptide therapies after receiving the treatment.

LS: I assume they have to come to your office to continue the neuropeptide treatments?

LM: Actually, we have different types of peptides. Some of them are injectable, subQ. There's a couple of options. Sometimes when they come in for their stem cells therapies, we'll have them leave with peptides for a few months’ duration. Or sometimes we can actually send peptides to their homes afterwards. So it really depends on where the patient is, ease of delivering these peptides, and such.

LS: Can you tell me a little bit about and name some of the peptides that you use?

LM: Definitely. One of the peptides that has shown a lot of potential and benefit in neuro conditions is Thymosin beta-4. It's from the Thymosin family, and it can actually upregulate repair processes. It has a lot of studies specifically on improving or helping repair myelin and oligodendrogenesis. It's one of the peptides that we use a lot for stimulating repair, and specifically for neuro it does it well. There's another peptide which is not specifically a neuropeptide, but it works wonders in terms of repair, which is BPC-157. This peptide generally speaking will just ramp up repair in the body. I like to integrate it a lot when we do treatments be it neuro or otherwise. The BPC does help a lot with that. And then we have other types of peptides that may be integrated into the neuro treatments, for example, the IGF secretagogues, growth hormone secretagogues. We know growth hormone is a very powerful hormone for repair in general. And raising IGF-1 levels can have a really positive effect. So sometimes, depending on the patient, we will upregulate IGF-1 through these secretagogues with the expectation that it'll help improve repair processes in the body. Also, Cerebrolysin, which is a combination of peptides, neurotrophic factors, such that when administered continuously can help improve nerve growth factor concentration in the body. It does really target the CNS with good results. There are quite a few peptides that we use on an ongoing basis that really can make a difference in some of these patients.

LS: I understand that this will depend somewhat on what you're treating and the peptide that you're using, but how long on average would you expect that a patient would remain on a neuropeptide?

LM: Usually, on average roughly speaking we want them at least three months on treatments. Some of these peptides we might be more aggressive in the initial weeks and then taper down gradually. And some of these peptides we might actually keep them on for three to six months as part of the maintenance protocols. But, usually you expect to see results within one and three months with these peptides.

LS: Well, thank you, Dr. Martinez. These are both very exciting frontiers of treatment for some generally considered untreatable conditions. Is there anything else that you would like to be sure we know before we end?

LM: I'm very optimistic about a couple of things. One, I'm very optimistic about what we're doing and what the future holds. As we continue to advance knowledge and develop more precise treatment protocols, we will continue to achieve even better results. Sometimes results will be affected by if patients can complete or not complete ongoing protocols. Then the other thing is on the regulatory side, it is a bit frustrating and everyone should be made aware of the challenges that we have within the US regulatory space. As you may probably know, a lot of these therapies have become more restricted in an FDA territory, including peptides now. We've started a non-profit to try to help save peptides because a lot of them are being targeted by the FDA so that we cannot have them available for our patients anymore.

And one last thing, again going to the US regulatory space, I think it is important that practitioners understand which products really are stem cells therapies and which are not. I often see a lot of products that claim to have live stem cells and they technically do not have these cells. Practitioners buy these products and inject patients with apparently live stem cells. A lot of education and research has to go into what is being used and how.

LS: Can you recommend a couple of trustworthy resources for that kind of research?

LM: Yes. I would be happy to. I can send you an email with some websites that can be used by practitioners looking for references.

LS: I really appreciate that. Thank you very much.

LM: My pleasure. We'll be in touch.