Interview with Samer Fakhri, M.D., Associate Professor and Otolaryngology Residency Program Director, The University of Texas Medical School at Houston

Topic: Using Cord Blood Stem Cells to Potentially Treat Hearing Loss - FDA-Regulated Phase I Safety Study

Samer Fakhri, M.D.

CAROLYN SMAKA: Today I'm speaking with Dr. Samer Fakhri, a board-certified otolaryngologist, Associate Professor, and Director of Residency Training in Otolaryngology at the University of Texas in Houston, in affiliation with Memorial Hermann-Texas Medical Center. In addition, Dr. Fakhri has clinical responsibilities and conducts research.

Dr. Fakhri is the principal investigator on the first FDA-approved Phase I safety study on the use of cord blood stem cells to potentially treat hearing loss in children, at Children's Memorial Hermann Hospital in Houston.

Dr. Fakhri, thank you for your time. Can you give us more detail about the purpose of this study?

SAMER FAKHRI: Yes, this is the first FDA-regulated Phase I safety study to look at the use of cord blood stem cells to potentially treat sensorineural hearing loss in children. I need to emphasize that this is a Phase I study, so right now we are looking at the safety of infusing autologous cord blood to potentially treat this kind of hearing loss. The term autologous refers to the fact that we are using children's own umbilical cord blood stem cells that were banked at birth.

We just started this study in January 2012, and currently have one patient enrolled. We are approved by the FDA for 10 patients, aged between 6 weeks to 18 months, that have acquired or congenital hearing loss. We'll exclude children that have genetic hearing loss and those that have syndromic hearing loss.

After children are qualified and enrolled, they will undergo a battery of tests including an audiological evaluation including OAE and ABR testing, an evaluation by a speech-language pathologist, and an MRI. The infusion will then take place in a hospital setting. The children will be observed over a few hours for any potential adverse effects. We will follow these children over the course of a year, with a number of visits. The follow-up will start with the child's own pediatrician, and we will see them back at one month, three months, six months and one year. We will repeat the audiologic testing, and at one year we will also repeat the MRI, which looks at specific sequencing to see if there are any potential changes in the auditory pathways to the brain.

As I mentioned, our primary point of interest is to look at the safety of an autologous cord blood infusion. Secondarily, and later in the study, we will look at whether this was beneficial for the hearing loss.

SMAKA: Regarding the safety, what would be the potential risks?

FAKHRI: Since this is an autologous transfusion, using the patient's own cord blood, the risk of rejection is very small. However, since we're infusing cells, there is potentially the risk of a reaction such as a rejection-type response, which is extremely unlikely, or allergic-type reactions.

SMAKA: Assuming the safety portion of the study shows that this is indeed safe, let's discuss the potential for hearing loss treatment. What research has been done that would show this might be a promising treatment?

FAKHRI: There is not much data yet on whether this form of therapy, using cord blood stem cells, is beneficial for hearing loss. However, there is a 2008 study that showed some significant effects of stem-cell infusions on animals with hearing loss (Revotella et al., 2008).

In this study, researchers from Italy and the U.K. induced hearing loss in mice using ototoxic medication as well as noise. They infused half of these mice with human stem cells, and followed the mice, sacrificing them at various points in time, up until about two months post infusion. They found that in the mice that were infused with the stem cells, the organ of Corti was actually reorganized, almost back to what you'd expect in an intact animal. The group that did not receive the infusions had a lot of hair cell loss and disruption in the organ of Corti.

That was the proof of concept for our research trial. There is ongoing research at our institution into other applications of stem cells, looking at cerebral palsy and traumatic brain injury, for example.

SMAKA: What is thought to be the underlying mechanism by which these stem cells reorganized the cochlea in the study you described?

FAKHRI: The hypothesis here is that these stem cells could act in one of two ways: they could become the specialized cells of, let's say, the inner ear. They would become hair cells. That is one theory or one proposition.

The other proposition is that these stem cells have the capacity to help the cochlea repair the injury. By replacing or regenerating cells, specifically fibrocytes of the inner ear, the stem cells support the body's own way of dealing with injury.

SMAKA: Since genetic hearing loss accounts for roughly half of all sensorineural hearing loss and is not included in this study, what are some of the causes of cochlear hearing loss that may be potentially treated with stem cells, should it someday prove effective?

FAKHRI: As you know, some possible causes of cochlear hearing loss in infants at birth or shortly after birth could be related to viral infections, bacterial infections, ototoxic medications, and decreased oxygenation, for example. So these are some of the causes we would expect to see in the infants who would enroll in the study. Exposure to noise or trauma could also cause cochlear hearing loss, but would be less likely to be present in infants.

SMAKA: What degree of hearing loss are you looking for in the patients you enroll in the study?

FAKHRI: We are looking at moderate hearing loss or greater, through profound loss.

Initially in developing the protocol we had considered all degrees of hearing loss. But we also wanted ideally to use some audiological test that would have a binary outcome that we could look at pre/post treatment.

Otoacoustic emissions (OAEs), for example, would be a good test to use in this type of research. If OAEs were absent pre-treatment, and present after treatment, it would be a nice endpoint measure to use. We know that with mild hearing loss OAEs are likely present so the same result would be found pre/post treatment.

SMAKA: We also know that in general, prognosis for a mild hearing loss with current hearing loss solutions such as hearing aids is excellent, while with more significant degrees of hearing loss outcomes may be more variable, depending on many factors.

FAKHRI: Yes. The current solutions for diminished cochlear function - mainly cochlear implants and hearing aids - try to amplify residual hearing or bypass the cochlea. The main potential advantage of using stem cells (based on the research that was done in animals and as well as some preliminary data from the brain injury or cerebral palsy studies) is that they may repair damage and restore normal hearing, by repairing the damaged organ. We do not currently have any therapies that restore hearing to its normal pre-injury level and that's the exciting potential of stem cells.

SMAKA: So the children enrolled in this study would still be using amplification as appropriate during the course of the study, since this is a critical period for auditory brain development?

FAKHRI: Absolutely. The treatments are not mutually exclusive, they're complementary. Let's say that a child receives stem cells and it doesn't work, that child is still a candidate for cochlear implants. Even if a child is using a cochlear implant, they can still be infused with stem cells if it repairs the injury in the end organ. We know that the first 18 months of life is a very critical window of time for the development of speech, language and social skills. Children with hearing loss will need some form of amplification during this time as deemed appropriate by the audiologist so that they don't miss that critical window.

SMAKA: Dr. Fakhri, can I ask you a really stupid question here? When the cord-blood stem cells are infused, are they infused via a general blood transfusion, or somehow directly to the end organ?

FAKHRI: It's not a stupid question at all;it's a very good question. The cells are infused intravenously, so the next question is: How does an intravenous infusion of cells work to repair a specific end organ, like the cochlea?

In the mice study, they were infused intravenously. From that study as well as other stem cell research in brain injury and cerebral palsy, we have some preclinical evidence that the stem cells actually go or are recruited to the site of injury by a variety of molecules, such as chemokines or others. In a way, these stem cells hone in on the site of injury to support the body's own repair mechanisms.

SMAKA: It sounds like science-fiction, it is so fascinating. Do you happen to know about what percentage of births bank their cord blood?

FAKHRI: I don't have those statistics. The company sponsoring this study is Cord Blood Registry®, which I believe has about half a million stored cord blood.

SMAKA: Should parents be banking cord blood?

FAKHRI: At this point we cannot provide a strong recommendation for it, and it is something that is left to individual parents' choice. There is a financial consideration;it costs money to store cord blood. Another way to look at it, is that for parents that can afford it, why not? It's like storing your own blood for later use. The likelihood of using stem cells in any individual is very low, but when they're needed they're very valuable.

In 2007, the American Academy of Pediatrics put out a position statement, not necessarily recognizing that cord blood should be stored. I think if these studies on cerebral palsy, traumatic brain injury and hearing loss show benefits of stem cells, the recommendations will likely change and then storing cord blood will likely become more widespread.

SMAKA: When do you anticipate this study will be concluded?

FAKHRI: Each study participant is followed for 1 year, and we're planning on enrolling at the rate of about 1 patient every month or two. So, it will be approximately two years to complete the study with all 10 patients.

SMAKA: Excellent. I hope we can follow up with you down the road to hear the progress of this really exciting research. Thank you for the opportunity to speak with you today.

FAKHRI: Thank you, Carolyn.

References

Revotella, R.P., Papini, S., Rosellini, A., Michelini, M., Franceschini, V., Ciorba, A., et al. (2008). Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise. Cell Transplant, 17(6), 665-78.