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Q&A: The Lesser-known Maladies of Spinal Cord Injuries

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shutterstock_96976301-300Last month, David Sharp and his fellow colleagues at the Albert Einstein College of Medicine, Bronx, N.Y., received a $1.2 million grant from New York State to advance their promising technology for treating paralysis and other effects of spinal cord injuries (SCI).

The grant is one of nine totaling $5.7 million announced by N.Y. Governor Andrew Cuomo. The funding will be administered by the New York State Spinal Cord Injury Research program, and represents the first round of competitive awards since funding was re-instated for the program in 2013.

Sharp recently spoke with Laboratory Equipment’s Editor-in-Chief Michelle Taylor about what the funding means to him and how he intends to use it to further his promising research.

Michelle Taylor: What does receiving this grant from New York State mean to you?

David Sharp: Firstly, this is a multi-disciplinary, multi-PI award, so this grant gives me the opportunity to work with two fantastic project co-directors, Sylvia Suadicani and Kelvin Davies, both in the department of Urology here at Einstein. We all bring something very different to the table with complementary expertise in neuronal cell biology, bladder, bowel and sexual function, but share a passion for reducing the suffering associated with spinal cord injury (SCI).

Secondly, I have friends with family members who have suffered with SCI for years. The chance that my work could make a difference for them is extremely satisfying on a very personal level.

And finally, neural regeneration is just a fascinating topic. As a basic cell biologist, it’s particularly exciting to see that my work could directly impact human health in the not too distant future.

MT: What will you do with the money to further your research?

DS: The funding will allow us to advance our research in animal models for a treatment for SCI. Our goal is to develop a therapeutic that repairs neural damage after injury and improves some functions.

Although the inability to stand and walk is viewed by the general public as the major disability associated with SCI, the loss of proper bladder, bowel and sexual function also rank as major determinants of patient well-being, with recovery of these functions listed by SCI patients as a top priority.

Our future research will translate some of our remarkable proof-of-concept findings into a novel clinical approach for treatment of SCI with its numerous associated morbidities. We plan to optimize treatment regimens for recovery from both acute and chronic SCI and to fully determine the molecular mechanisms underlying regeneration.

MT: What previous research have you done on SCI and what were the conclusions made?

DS: I got my Ph.D. in neuroscience in the 1990s and have been generally interested in how neurons develop, differentiate and regenerate for more than 20 years. In the past few years, we’ve found that a class of proteins called fidgetins are normally utilized to inhibit axon growth and neuronal regeneration. They do this by suppressing the formation of structural struts, called microtubules, which normally support axon growth. When we temporarily force neurons to stop making certain fidgtetin proteins, using an approach called RNAi, the neurons become highly regenerative—when done after spinal cord injury in rats, we’ve been able to induce a dramatic restoration of locomotion and urogenital function.

MT: How will your previous research play into your new research? And what are some specific goals of your new research?

DS: Our new research builds directly on the initial spinal cord injury experiments described immediately above. We now want to determine the best ways of inhibiting fidgetins after injury, figure out the time period within which fidgetins can be targeted to promote functional recovery after SCI—in other words, is our new therapeutic particularly useful for acute injuries or can we also apply it to treat chronic sufferers of SCI (people injured months or even years ago)?

MT: How will you go about reaching these goals?

DS: First, we are working with formulations experts to identify the most efficient and easy to use approach to inhibiting fidgetin proteins at the site of SCI (currently we’re using siRNA encapsulated in nanoparticles). Second, we use animal models of spinal cord injury to test and compare the efficacy of these formulations to restore locomotion, bladder function and erectile function after the injury. Third, we will identify the best treatment regimens for inducing the most beneficial outcome—that is, determine the best concentration, frequency and timing of treatment applications, etc. Finally, we will determine any possible safety issues (i.e. toxicity) associated with our different formulations.

MT: How do you advance your research from bench to bedside?

DS: A practical goal of the work supported by this grant is to generate data in support of an IND (Investigative New Drug) proposal to the FDA. This has to be approved before any human trials can be conducted. Once we have the IND in place, we have clinicians at New York area hospitals who are interested in partnering with us to perform the clinical trials.

MT: What potential effect could your research have on health care costs?

DS: There are massive costs associated with the long-term care of SCI victims, approximately $3 billion a year in the United States alone. Even partial restoration of bodily functions lost after the injury greatly reduce the cost of this long-term care.

MT: What are a few real-world implications of your research?

DS: There are approximately 270,000 people in the United States living with SCI, with 12,000 new cases each year. In addition to the significant financial burden, there is obviously an enormous human cost in loss of quality of life and well-being. We are hopeful that our research will lead to treatments that can help alleviate this burden and improve lives.

By: Michelle Taylor, Laboratory Equipment’s Editor-in-Chief

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