Future Regenerative Therapies for Hearing Loss: Your Questions Answered by Dr. Jackler, Part I

Dr. JacklerDr. Jackler, Sewall Professor and Chair of the Department of Otolaryngology-Head & Neck Surgery, and the SICHL research team receive questions daily on the current state of our research, the goals and the possible outcomes. As such, we thought that readers might find it helpful to have questions about possible future regenerative therapies for hearing loss, answered here on our blog.

Below you will find a Q&A with answers from Dr. Jackler. We will post this interview in two parts and hope that you will find that your questions about our research are answered. However, if you have further questions, please feel free to leave them in the comments section below, or email.

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Q1 – What is the projected timeline for Stanford to begin clinical trials?

Dr. Jackler – Our aspiration is to begin clinical trials of effective means of overcoming hearing loss within the coming ten years.

Our plan is to design sophisticated and targeted therapies based upon advanced knowledge of inner ear development to arrive at effective therapies with a high probability for success. Our unique collaboration allows us to reach for these goals. It is possible that a promising solution will arise at an earlier time and we will certainly exploit any biologically sound and safe techniques which arise.

Q2 – I have read in the news that there are already trials underway of stem cell therapies for hearing loss. Why isn’t Stanford currently involved in human trials?

Jackler – In the world of stem cells regeneration it is a certainty that some may exploit the public beliefs that stem cells are magical and will automatically work without precise preparation to make this type of therapy safe and effective.

While some groups may try imprecisely targeted therapies, such as cord blood, before our projected timeline for trials, we think these unlikely to be successful. A large amount of painstaking research has been conducted to establish the conditions necessary for inner ear regeneration.  We only wish it was so easy that simply infusing primitive stems cells, as is currently being done, into the vascular system would work.  Unfortunately, getting stem cells to become hair cells is a complicated and difficult process which requires a number of sophisticated steps to coax primitive cells to mature into hearing cells.  Sadly, it does not happen magically as would be necessary for these early trials to work.

Q3 – What steps would SICHL have to complete before they felt it was safe and advisable to begin clinical trials?

Jackler – We need to be able to produce an abundance of new hair cells within the deaf cochlea, together with supporting structures, and link them to the hearing nerve. This requires that we stimulate progenitor cells – cells with the ability to mature into hair cells – to transform, or morph into functional hair cells.

Many challenges remain, each of which appears solvable with a concerted effort. It will be important that the new sound sensing cells be correctly positioned and oriented within cochlear spiral to respond appropriately to sound entering the inner ear. As making cells proliferate and mature requires both an on and off “switch” this is an important safety consideration. For example when you stimulate cells to divide robustly and they continue dividing it can effectively become a cancer-like condition. So the need for controlling the proliferation, so that it only acts as long as necessary to create a new inner ear, is fundamental to safety. This is a reason why we want to keep treatment confined to the inner ear so that other cells in the body do not get exposed to the proliferation technique or the way we stimulate inner ear has to be precise in targeting unique to inner ear cells.

The danger of simply infusing cord blood or embryonic stem cells is that they are neither specifically targeted to inner ear nor is the delivery confined to the inner ear, esspecially if the cells come from another person. This could lead to a dangerous situation of uncontrolled proliferation of foreign cells. The techniques we are pursuing are highly directed and specific towards the inner ear.

The goal of creating specific inner ear targets is well along, but we need to develop delivery mechanisms that are not injurious to the damaged cochlea to place molecules and or cells within the cochlea. We also need to control the process precisely and to orient the process in the correct position and polarity. These are all major challenges, but we have clear pathways forward for meeting them.

Q4 – Why do you think that Stanford is uniquely positioned to cure hearing loss?

Jackler - Stanford has assembled an interdiscplinary team of scientists and engineers drawing upon expertise from many different domains for the shared purpose of curing hearing loss. Leveraging the world class expertise of scientists from fields unrelated to hearing but central to issues of regeneration is a major factor in favoring Stanford as a center for innovation in this area.

In addition our core scientific team is the world’s leading group focused upon restoration of hearing through regeneration means. Our laboratory leader, Dr. Stefan Heller is world renowned for having first described the presence of stem cell within inner ear and demonstrating that they could be reproduced in stepwise fashion to link with the hearing nerve and mature.

Q5 – What kinds of hearing loss will it be possible to cure?

Jackler – We have the ambitious goal of curing virtually all forms of inner ear hearing loss. It is interesting that almost all forms of hearing loss ends up in the final common pathway which is loss of hair cells but with preservation of the hearing nerve and the overall structure inner ear.

In non-genetic hearing loss, where there are no fundamental flaws in the person’s DNA effecting hearing, it will be possible to stimulate their own cells remaining within the inner ear to transform into hair cells.

In genetic loss, where the DNA is flawed, the challenge is greater because the correct DNA sequence is needed to re-create an inner ear – and we have a couple of choices. One is, genetic engineering to replace the incorrect DNA sequence through gene therapy. The second possibility is to implant cells with correct DNA, taken from the laboratory, into the inner ear. Finally we are excited about the possibility of directly replacing the gene product, the missing protein that the gene would have produced within the inner ear, by other means. We can fix diabetes by giving supplemental insulin. Imagine that we may be able to infuse within the inner ear molecules to provide what is missing or even engineer patient’s own cells to produce an abundance of the missing material that is crucial for hearing.

Check back soon for Part II of this Q&A, which will cover issues surrounding cochlear implantation, Meniere’s disease and ways in which you can help Stanford achieve this exciting goal of curing major forms of inner ear hearing loss.

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