Questions and Answers:
1) First off, why are we targeting HSV-1 ocular herpes (herpes stromal keratitis) first and not testing the ribozyme against oral herpes right away?
"There are actually several reasons for this strategy. First, and foremost, is that there are currently no accepted animal model systems to test the ribozymes against recurrent oral herpes. In fact, the only animal model in which one can reproducably produce clinical reactivation of an HSV-1 herpes infection is the rabbit eye model. Therefore, in order to prove that the ribozyme can block HSV-1 recurrent disease (and gather data acceptable to the FDA in support of that claim) , we are focusing on testing the ribozyme in that model. A second reason we focused on ocular herpes first is that the number of cases of stromal keratitis that occur each year (<50,000) qualifies it for Ophan Drug Status with with FDA. This would be a huge advantage in going forward to clinical trials since it would require smaller numbers of patients in the trials, fast-track the approval process, and save millions of dollars in clinical trial costs.
A key concept here is that the very same ribozymes that are used against HSV-1 in the eye could be used to treat oral herpes (or HSV-1 anywhere else on the body). So if the clinical trials for the ribozyme against ocular herpes progress well then the burden of testing for using the same ribozymes against oral herpes would be much lower with the FDA since the proof of principle was already established with the ocular product. This is important since there is no animal model for testing oral herpes and the FDA would allow us to extend any data showing that HSV-1 was effective against recurrent disease in the eye to argue the likelihood that the therapy would also be effective in blocking oral recurrence and therefore merit clinical testing."
2) Why are we not targeting HSV-2 first?
"There is no question that many more people suffer greatly from HSV-2 genital herpes than from HSV-1 diseases. The main reason that we got started on HSV-1 first is that Dt. Tuli (a corneal specialist) came to Dr. Lewin and myself one afternoon on 2001 frustrated because of the number of corneal transplants she was performing on patients with HSV Stromal Keratitis because the current drug treatments don't work for that disease. That is really what got us thinking about ribozymes and got the whole approach started. While I was somewhat pessimistic that this approach would work initially, I felt sure that we could determine its efficacy in the well-established HSV-1 models that we had available. Anyway, we started weekly meetings as a group to brainstorm and design the initial experiments and it came together much better than any of us though possible.
If the HSV-1 ribozymes work at blocking HSV-1 recurrent disease, i think it is very likely that the same approach can be used to treat HSV-2 genital herpes. The same viral target (UL20) should be effective, but the ribozymes will contain slightly different sequences because HSV-2 UL20 is slightly different than HSV-1's version. We have already started the design of the HSV-2 ribozymes and any funds raised for HSV-2 research would be used to advance this line of work and take this approach into animal testing as soon as possible."
3) What other sources of funding are we seeking?
"We have applied to the NIH for funding for this project, but the project was deemed too far along for "R01-type funding" since it is now viewed to be in a "product development phase". At the same time, we have been advised that without proof that the ribozymes can block recurrent disease we are not in position to be successful for an NIH small business grant (SBIR), or to seek venture capitol funding. VC folks have said our project would be very attractive for clinical trial funding if we show efficacy in blocking recurrent disease (and the potential to block HSV-2). So I think you see why we are so keen to try to get funds together to allow us to fund the recurrent disease phase of the study"
4) Are you waiting until the HSV-1 fund hits the entire amount you need? Can it be funded incrementally?
"Unfortunately we really can't start until we have enough funds to pay the salary of the technician to help perform the day-to-day experimental tasks (including caring for the rabbits, preparing the ribozyme, and performing the analysis for ocular lesions and virus). We also need the supplies for cell culture and PCR for these analyses, and finally we need the funds for at least the first group of rabbits just to get started. That is why it has been difficult to initiate these experiments - they can't be done incrementally."
5) If the recurrence trials are a success what is the probability you will be able to get grant funding from NIH? U of F? Venture Capitalists? I thought you were going after the transitional science grant from U of F first?
"We have been told by several independent sources that if we have encouraging data from the recurrence experiments that we would be in very good position to secure larger grant funding as well as private investment funds. Yes, we do plan to seek funding (and guidance) from the UF CTSI grant. Basically if the reactivation studies are successful we plan to apply for multiple sources of funding to give us flexibility to move forward quickly."
6) "FDA would allow us to extend any data showing that HSV-1 was effective against recurrent disease in the eye to argue the likelihood that the therapy would also be effective in blocking oral recurrence and therefore merit clinical testing"
---Does this mean you could effectively conduct human trials on HSV-1 in other areas of the body (oral, genital) using the same Ribozyme you developed for Ocular purposes? How would this be funded? Would this be another 5 years or would this go quicker?
"Either an SBIR grant or venture funds would almost certainly include a parallel study arm to test and develop the ribozyme for a broader market (i.e oral and genital applications). And yes, this would speed up the timeline."
7) Will the virus still be able to shed and be spread to others with your solution?
"The virus will not shed and will not be transferable to others. It will loose its ability to cause disease."
8) How will you support the voting campaign?
"I have already thought about this and plan on utilizing my colleages as well as virology students. I will start brainstorming on other ways to get the word out."
9) What do you think of what the HCC is doing?
"The HCC has reenergized my work. We have had a delay in press since the first experiments and the HCC has caused a lot of buzz down here at the University of Florida. The team is very grateful for all your hard work. What you are doing is simply amazing. With the current momentum, I think that if we can get the funding within 3 months time we are going to be in a great position."
