Newswise — As a child, Michael Stone avoided sports. Now in his mid 40s, he's completed more than 100 triathlons, including 11 Ironman races, and 21 Xterra Triathlons—off-road triathlons that involve mountain biking and trail running.
Not such an unusual story perhaps, but the reason Stone shunned sports as a kid was because he couldn't see the ball, and his vision has progressively worsened so that he now is "legally blind."
"When I ride a bike or I'm running, I use my feet; I use every piece of information I can get through my other senses," Stone says. "I like to think of myself as the Forrest Gump of the vision world because technically I shouldn't have been able to do many of the things I was able to do."
Stone is straightforward about the many frustrations and challenges his vision loss has created. But, the two characteristics that shine through any conversation with him are an incredible tenacity to work around his vision-imposed limitations and a deep desire to make things better for others affected by blinding eye diseases. This sense of purpose infuses his approach to life. When he races, he raises money for research on eye diseases; he is a counselor and ardent advocate for people with blinding eye diseases; and he is an author whose book highlights the inspirational stories of people affected by eye disease.
Stone co-founded the Race to Cure Blindness, a fundraising program for Foundation Fighting Blindness (FFB), and he and his family are deeply committed to supporting research that will eventually lead to treatments and cures.
Despite being so involved in advancing research for blinding eye disease for many years, Stone did not have a definitive diagnosis for his own condition. In 2003, he was told he had cone rod dystrophy, a retinal condition caused by many different gene mutations, but he did not know which gene was affected in his case.
In the past year, Stone’s situation has changed. Through a series of coincidences and a collaboration with researchers at the University of Iowa in Iowa City and Columbia University in New York, Stone and his family now have answers about the true nature of the condition that affects them.
Connections and coincidences It all started with a chance conversation that reconnected Stone with his old school friend, Alex Bassuk, MD, PhD, now a pediatric neurologist with UI Children's Hospital and a genetics researcher at the UI Carver College of Medicine.
"I grew up with Michael, he is very good friends with my sister," Bassuk says. "They were talking about his eye disease and he mentioned that it was genetic, and my sister said, 'Oh, my brother does genetics and even works on eye diseases. You should talk to him.'"
From that initial conversation, Stone and his siblings ended up visiting Iowa City in December 2012 to meet with Bassuk and Vinit Mahajan, MD, PhD, a UI ophthalmologist and expert in inherited eye diseases. The scientists took DNA samples and Mahajan conducted thorough eye exams.
The final link in the chain was the connection Mahajan and Bassuk had with Stephen Tsang, MD, PhD, a physician-scientist and expert in retinitis pigmentosa at Columbia University in New York. This connection provided a critical opportunity to gather several generations of Stone's family in one place for testing—something that had never happened.
"Even in an age where genetic testing for disease has become incredibility sophisticated, the old school approach of examining family members—both affected and unaffected individuals—is a critical aspect in diagnosing an inherited condition," Tsang says.
"Michael's family is scattered across the country, so no one had examined the family all together, and with a condition that you think is inherited, that's usually very valuable to do," Mahajan adds.
Stone, his siblings, and his parents went to Columbia University for clinical exams, including specialized imaging of the family members' retinas, as well as blood draws to obtain the samples needed for the next-generation, whole-exome DNA sequencing. Mahajan went with the family.
"(Vinit) came out for that and kind of held our hands through the experience," Stone recalls.
With the results of the exome sequencing in hand, the three scientists combed through the list of possible gene variants, seeking one that fit the clinical profile they'd created through their detailed examination of Stone and his family members. Bassuk recalls the excitement of the moment as the three colleagues from their separate offices—two in Iowa, one in New York—emailed back and forth: "How about this one?" "What about that one?" Then, suddenly, hitting on a variant in the RPGR gene and realizing that it was a perfect fit.
About a year after their first meeting with Stone and his family, the researchers were able to show that the family's inherited eye disease is caused by a new variant in a gene called RPGR. Although this variant is new, mutations in the RPGR gene are already known to cause retinitis pigmentosa. The new variation causes x-linked retinitis pigmentosa, meaning the disease is passed on through the maternal line. The finding was published Jan. 31 in the British Journal of Ophthalmology.
"It's been a combination of the gumshoe detective in the field tracking down clues and the forensic pathologist in the lab. A high-tech, low-tech combination," Mahajan says.
Several hundred genes can cause retinal degeneration, which affects millions of Americans. Although there currently is no treatment for the newly discovered variant, identifying the specific gene can help direct the research and may ultimately lead to a treatment.
Stone notes that successful gene therapies developed for retinal diseases—such trials currently are under way—might open the door for successful treatment of many other inherited diseases.
The Stone family has provided philanthropic support through the UI Foundation to advance the UI team's research, which they believe will lead to future treatments and cures.
Being able to help people is an underlying motivation for many physicians and scientists, but Bassuk says that this opportunity to directly help a friend was definitely special.
"It was really nice. I've been doing this for 28 years and I've not had this kind of experience before," he says.
For Stone, who is set to compete in his 12th Iron Man race in New Zealand at the end of the month, having an answer that explains the disease that has affected his family for generations has been an emotional experience but also a very important step.
"There was definitely a process, and it continues to be a process," he says. "There is something very liberating about knowing what it is that you have—to take a very uncertain world and create a little bit of certainty. It reignites a purpose into your life, so it's very important, but it also reignites the concept of hope."
As someone who is passionate about helping others overcome the limitations imposed by eye disease and ensuring that patients and families know they are not alone in their struggle, the idea that the researchers are now advocating for him and for others affected by these disease is also very powerful for Stone.
"To know that you have some champions out there fighting for it is huge," he says.