IN 800 WORDS

Living in “an exciting age of understanding disease”

In 800 Words is a succinct, timely talk with a need-to-heed KOL.

Paul A. Sieving, MD, PhD, has been director of the National Eye Institute since 2001. An active clinical trial investigator* with nearly 200 titles listed in PubMed, Dr. Sieving has a varied educational background: history, nuclear physics, a bit of law school, his MD degree and a PhD in bioengineering.

OM: The NEI’s Audacious Goal Initiative (tinyurl.com/gph636s) is about restoring vision by regenerating the retina. Is there one audacious goal that is more important than the others, that could be described as the keystone?

PS: There are several keystone events that involve learning how to manipulate nerve cells and make them grow from stem cells. The next challenge will be to get these to connect to each other in appropriate ways to convey vision from the first stage of capturing light until it is processed by the brain. Beyond that, meeting our goal means establishing new medical therapies for people. We won’t reach the goal in one giant step. There will be many subordinate goals along the way — many will be breakthroughs in their own right.

OM: Do you expect any solutions to ganglion cell restoration for one disease to be transposable? The NEI also wants to solve the underlying disease that is causing the cell destruction, correct?

PS: We would welcome a one-size-cures-all approach to therapy, but that is not something we currently foresee. Once AGI enters the translational phase, clinical trials will test specific therapies for specific diseases. Having said that, the investment in imaging, basic biology, informatics and other key areas will let us tackle the full spectrum of degenerative eye diseases.

OM: Looking at the five winners of the AG Challenge, not all were ophthalmologists. It seems the NEI is interested in breaking down silos. Are other NIH divisions seeking guidance from you for their own audacious goals project?

PS: From the beginning, the NEI AGI actively solicited input from a broad range of scientists and thinkers. In November 2015, we launched the AGI Seminar Series in Neuroregeneration on the NIH campus to foster trans-NIH collaborations.

OM: You have been a researcher for many years. So, what do your instincts tell you: Will the results from the audacious goals initiative possibly serve to be helpful to the boomer diseases: glaucoma, AMD, DR?

PS: What we learn through AGI will inform strategies to prevent and treat many eye diseases. Vision loss from glaucoma, AMD and DR principally affect older populations. But we know these diseases manifest earlier in life, before advanced age, and progress over a long duration. AGI-directed research, such as the currently funded imaging projects, will help to tell us about what triggers these diseases. And these new tools and techniques will allow detection during early stages of disease before vision is affected.

OM: Several studies over the past year have shown how signs of Alzheimer’s can appear in the eye early in the disease. Other studies have linked associations between rheumatoid arthritis, AMD and osteoarthritis. Have you formed collaborations with other NIH divisions to look at Parkinson’s, open-angle glaucoma or Alzheimer’s, for example?

PS: The intersection of aging and disease is a hot topic. We discussed this at the AGI development meeting in 2013. The single greatest risk factor for many diseases is advanced age. Eye disease is no exception. A team funded by the NEI and the National Institute of Neurological Disorders and Stroke recently published in Science the discovery of a compound that reverses cataracts. Interestingly, the researchers reported that the compound’s mode of action could have implications for other protein misfolding disorders, such as Parkinson’s and Alzheimer’s. The discovery highlights the importance of collaboration, and that disease is not confined to specific organs.

OM: Considering that the AGI and the Obama Administration’s BRAIN Initiative — an attempt to map how individual cells and the brain’s circuitry interact in space and time — what is your personal assessment of this era in science in which you find yourself?

PS: This is an exciting age of understanding disease at the biological level and devising therapies to try. I believe the 15 years of the new millennium [herald] a golden age of discovery. In these few years, we saw the completion of the Human Genome Project, the dawn of induced pluripotent stem cell research and the realization of gene therapy.

These advances and others signal a paradigm shift in the way we treat disease. The current era will advance the next generation of biomedicine beyond proof-of-concept and into the clinic. It will be an exciting journey. OM

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