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Introducing Todd E. Golde, M.D., Ph.D.

 

 

 

Todd E. Golde, M.D., Ph.D., is currently the Director of the Center for Translational Research in Neurodegenerative Disease at University of Florida (Department of Neuroscience) where he directs a robust program of scientific discovery aimed at translating basic discoveries in neurodegenerative disease into diagnostics and treatments for patients. Dr. Golde has joined the Facial Pain Research Foundation research team as a Co-Investigator on the “In Search of a Cure: Finding the Brain Signature Centers that Cause Trigeminal Neuralgia”.  The project is directed by Dr. John Neubert at the University of Florida McKnight Brain Institute.  Dr’s Mingzhou Ding, Marcelo Febo, Robert Caudle are also Co-Investigators.  Dr. Andrew Ahn, Chief Scientific Officer Pain/Headache, Eli Lilly & Co. is a Consultant.  I asked Dr. Golde to write a brief descriptor of his work on this Foundation Research Project.--

 

Michael Pasternak, Ph.D., Trustee


 

Towards Gene Therapy for Trigeminal Neuralgia

 

By Todd E. Golde, M.D., Ph.D.

 

If one reads the entry for Trigeminal Neuralgia (TN) on Wikipedia, the second paragraph begins with the statement “Although TN is incurable, its symptoms can be managed ….” Many who suffer from chronic TN will endorse the first part of this statement, but likely strongly disagree that symptoms can always be managed; however, gene therapy-based approaches may in the not too distant future offer better outcomes for patients with TN whose symptoms are not well controlled by current standards of care. Indeed, leveraging the world-class expertise in gene therapy at UF, multiple UF faculty are teaming up to evaluate whether novel gene therapy approaches can translate into transformative new therapies for TN.  TN is a potentially ideal candidate for development of novel gene therapies targeting pain, given its focal nature and the accessibility of the trigeminal nerve to direct injection of vectors that will carry genetic elements into the affected nerves.  Drs. Neubert, Caudle, Levites and Golde have already teamed up to show that in rodent models using gene therapy vectors already available, one can easily deliver genes selectively and extremely efficiently  to the trigeminal nerve. Notably, once delivered to the nerve cell, the genetic material within the gene therapy vector is stable. Thus, a single treatment could provide a lifetime of relief.

 

Although the UF teams’ studies are in very early stages, all involved in the project are excited and optimistic that they can develop a road map that will lead to a more effective therapy for chronic severe TN. Their next step is to see whether one can silence pain signaling in the trigeminal nerve following gene therapy. Such proof of concept studies are already underway. In these studies the team will deliver engineered proteins that can either induce or blunt pain responses in the trigeminal nerve. The engineered proteins that are being used respond to a modified drug in a way that either silences neuronal firing or enhances it. Thus, once delivered to the nerve cells, the response of that cell can be modulated and the team can see if the rodent’s response to facial pain can be blunted or enhanced.

 

If these critical experiments are successful, the next steps will be to develop a gene therapy that is potentially translatable to the human studies. The engineered proteins used in the proof of concept studies currently underway cannot be used in humans; however, one of the real advantages of the paradigms the UF team is establishing is that multiple different approaches and targets can be rapidly evaluated. Especially intriguing is the potential ability to use new gene editing tools developed by UF faculty member Dr. Edgardo Rodriguez to permanently delete a key protein involved in pain signaling within the trigeminal nerve. Such an approach might spare other important functions of the trigeminal nerve while selectively blocking pain signaling. Ultimately, the investigators involved believe that this highly targeted approach can overcome many of the problems associated with traditional  pharmacological based approaches to pain and  actually lead to markedly improved outcomes or even cures  for TN and other focal chronic pain syndromes.


 

 

 

 

 

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Success in answering critical questions about the role of genes in TN and other

nerve-related facial pains relies on private support. Here are ways in which donors

at all levels can join The Facial Pain Research Foundation in finding a solution:

  • Support full expenses of one patient      in the study:     $1,770
  • Pay for the genotyping of one research      participant:    1,100
  • Help with the phenotyping costs for      one participant:     600
  • DNA extraction from one person’s      saliva samples           40
  • Pay for saliva kit & shipping cost      for one participant      30
 

 

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