Dr. Dryja is an ophthalmologist with subspecialty training in ocular pathology and molecular genetics. He is a member of the faculty at the Massachusetts Eye and Ear Infirmary and a professor of ophthalmology at Harvard Medical School. He previously served as the Global Head of Ophthalmology Research at the Novartis Institutes for BioMedical Research.
Hereditary ocular diseases
Dr. Dryja, a member the U.S. National Academy of Sciences, is one of the country’s most successful scientists in the area of molecular genetics of hereditary ocular diseases. Digging deeper into the 22-page résumé, we find many accomplishments. When asked for the feat that he is most proud of, Dr. Dryja answers: “I am proud of finding compelling evidence for the recessive nature of oncogenic mutations at tumor suppressor genes like the retinoblastoma gene – that was in 1983. Another major step was the identification and cloning of the retinoblastoma gene – one of the first human genes ever cloned based only on its chromosomal location.”
“I also was the first to discover a gene responsible for nonsyndromic retinitis pigmentosa. That first identified gene was the rhodopsin gene, and it turned out to account for about 10% of all cases of retinitis pigmentosa. Over the years, my group subsequently identified 15 other genes responsible for forms of retinal degeneration and retinal dysfunction.” As this is one of the areas that ProQR is working on, Dr. Dryja feels ‘at home’ with the Dutch-based biotech company. “I feel very comfortable in my new role in this company. I discovered or intensively evaluated some of the genes the scientists of ProQR are currently working on.”
Developing RNA-based therapeutics
The discoveries and other milestones underline the massive expertise Dr. Dryja brings to ProQR’s SAB. ProQR expects this expertise to be of substantial value as the company continues developing its RNA-based therapeutics for a growing number of ophthalmic indications. When asked about the areas in which he intends to contribute, he points out the relevance of the work he did for Novartis, as the Head of Research.
“I was responsible for selecting the drug targets, but also for leading the team that developed drugs or gene therapies for those targets and for testing them in phase 1 and phase 2 trials. From that period, I hope that experience will allow me to substantially contribute to the discovery of new therapies for genetic defects and especially on how to efficiently and safely test them in early clinical trials. I look forward to the discussions with the company and other members of Scientific Advisory Board about ProQR’s current and future course. I feel honored to help fuel ProQR’s ongoing quest in the ophthalmology area.”
RNA, a whole new category
What is Dr. Dryja’s opinion on what RNA technology can do for ophthalmic indications and the potential for therapeutics? “Pharmaceutical companies have traditionally relied on small molecule drugs based on hydrocarbon scaffolds. Twenty to 30 years ago antibody and other large protein drugs were added to the pharmaceutical armamentarium. RNA therapy represent a new platform for drugs as well as a new category of drug target. ProQR is exploring the exciting area of RNA therapy, and for some diseases, could turn out to be the optimal platform.”
Though the technology leads to promising findings, Dr. Dryja knows from his own experience that finding new RNA leads will be very challenging and sometimes discouraging. “I also found that seeing patients and learning about their experiences is crucial to maintaining ones energy and motivation. It also provides clues as to the best approaches to early clinical trials because one can learn what symptoms or signs of a disease are most important to patients and will be most likely to change when a new therapy is started.”
Exciting things in science
At his age, Dr. Dryja is entitled to relax and look back on his career, but he has no intention of quitting. Instead, he looks forward to a role that lacks most of the management and bureaucratic duties of a leader and instead concentrates on the clinical and scientific aspects of drug discovery. “There are so many exciting things happening in science, things that can bring the next breakthrough that will substantially help patients.” Things that allow for hope? Some patients are afraid to hope for too much. “Patients with currently incurable, devastating diseases are very vulnerable. Some have been disappointed over and over again by quack therapies or therapies that are promoted with great hyperbole before they are shown to be ineffective after being properly tested with scientific rigor. To patients, I try to be honest and compassionate. Like everybody at ProQR, I am eagerly awaiting any discovery that will eventually help stop or reverse genetic eye diseases like Leber congenital amaurosis, or LCA. That is my motivation.”
Dr. Dryja insists that he has many reasons for optimism. “For thousands of years, doctors had no clue about what caused diseases like LCA. Today, we do know about the basic causes of the diseases such as which protein is fundamentally abnormal or lacking, or which cellular pathways are defective. This knowledge is a huge advantage compared to what was available in the past to scientists working on therapies. And we are now living in a society in which pharmaceutical and biotech companies have the economic motivation to spend millions to dig deeper and to come up with therapies and drugs. Eventually, one of their approaches is going to work! There has never been an historical era when there was such a rational basis for predicting that worthwhile therapies are imminent.”
Invest in imagination
The young ProQR teams, Dr. Dryja insists, must utilize every bit of their imaginations they can muster to maintain their leadership in their field. “The advantage of youth is an amazingly fresh outlook on innovative approaches. The impression that success will come quickly encourages them to start projects that older, more experienced scientists would erroneously disregard as too difficult or impossible.”
“My advice to ProQR: you are exploring an uncharted wilderness with the potential to revolutionize the care of patients with blinding diseases. It will take years to find the right molecules suitable for clinical testing and then to test them in patients. There will be successes and failures along the way, but you need to keep up your morale. Celebrate small successes and learn from failures.”