Navigating Life with CRB1
Joseph F. Smith has been legally blind since birth. He lost what little sight he had in his mid-30s, when he learned he had Leber congenital amaurosis (LCA). Thirty years later, genetic testing revealed a mutation in his CRB1 gene, a diagnosis known as LCA8.
More than 40 leading experts in ophthalmology and gene research gathered virtually for more than five hours in February to share research and patient perspectives on CRB1 and identify the next steps to advance treatment for the patient community.
The CRB1 gene provides the body with instructions for making a protein that plays an essential role in normal vision. This protein is found in the brain and the retina, which is the specialized tissue at the back of the eye that detects light and color.
While the biology for CRB1 is particularly complex, early research produced the discovery of a new version, or isoform, called CRB1b. Preclinical studies give rise to new questions as to whether CRB1a or CRB1b expression, or both, should be the target of a gene therapy. Click here to view the webinar.
In his letter, Joe wrote: “I won the CRB1 lottery 76 years ago and spoke briefly during the webinar.”
When we spoke to Joe by phone, he wanted to know what he could do to reassure parents of children who are blind or visually impaired that they can thrive.
Joe earned a law degree from Cornell Law School after graduating as a math major at Alfred University in upstate New York. He worked at the New York City Corporation Counsel’s Office in the Real Estate Tax Division for three years.
While working, Joe began his teaching career at New York’s Dominican College where he taught a business law course. He taught law at the University of Baltimore Law School in 1973, and three years later accepted a job at Fort Lauderdale’s Nova Southeastern University School of Law, where he became a tenured professor and taught for more than 30 years.
He is retired, living in Florida with his wife of 51 years, Alice.
The Importance of Learning Braille
Joe’s 76-year journey began long before the enactment of the Individuals with Disabilities Education Act and the Americans with Disabilities Act, Congressional civil rights legislation prohibiting discrimination and guaranteeing that people with disabilities would have the same opportunities as everyone else. He said he was fortunate to receive scholarships from an earlier version of the Rehabilitation Act of 1973 to fund his higher education.
People with vision difficulty or other challenges must still vigorously advocate for accessibility and equality, but those roads were even bumpier in the past.
Before retiring, Joe developed a course on the rights of people with disabilities. He also created a program in which he supervised students working for organizations providing services for people with disabilities.
He understands that ever-evolving technology greatly helps people with vision loss, but he is a proponent of learning braille.
“One thing I do think is very important is that a child who is losing sight or is blind needs to learn braille. I know many educators will say with accessible computers, cell phones, and recorded materials, braille is unnecessary. My simple response is, ‘All that technology is available to sighted people, but they still use pens and pencils.’
“If you learn braille, you have something to keep in your mind. You have a physical image of the written word.”
With CRB1, Supportive Parents and Friends
Joe believes much of the credit for his success goes to his blue-collar parents who did not graduate from high school.
“I can’t imagine what it must have been like for them to find out I was blind and with no explanation as to why.”
Early on he could distinguish basic colors and he can still see red and orange in his mind’s eye.
Growing up in the 1950s, “back in the dark ages,” Joe said his parents knew that the local Catholic school was not going to work for him because it offered no resources. His mother wanted to wait a year for him to go to first grade, but his father said no. A learning disability kept Joe’s dad back a year because he could not read, prompting him to quit school in eighth grade to play baseball.
“He knew that education was important.”
Joe attended Lavelle School for the Blind run by Dominican nuns in the Bronx, leaving home Sunday nights and returning Friday afternoons, through eighth grade.
Lavelle served Joe well, but he wanted to attend a regular high school – any school that would take him, as mainstreaming was not a big goal back then and schools were not obligated to accept students who were blind.
He went to Archbishop Stepinac High School in White Plains run by the Archdiocese of New York. His senior year, another blind student was accepted to the school.
Math books in braille were in short supply and books in general were hard to get, so his mom read to him – a lot.
His dad also rarely said no to him trying new things. He rode around the neighborhood on his bike, enjoyed daredevil sledding, and loved cars in high school. His dad took him to an empty parking lot and taught him how to drive a stick-shift.
But the pièce de resistance for this self-described car nut came when he slid behind the wheel of an automatic BMW for the ride of his life on the skidpad at a defensive driving school.
“Truth be told, my wife was taking the course, but the instructors snuck me out for an unforgettable hour of bliss.”
I guess what I’m trying to say is a child who is blind should be encouraged to develop interests in and to try activities, which, at first blush, might not seem suitable for a child with limited or no sight.
His best friend in grammar school read him comic books, and as they got older, car magazines. They didn’t go to the same school, but they managed to get into trouble together and often double dated.
He excelled in math and thought he might be an engineer, toyed with psychology, and after Alfred University, decided to go to law school.
Practicing and Teaching Law
Joe met Alice on a blind date in his second year of law school when she was a sophomore at New York’s Wells College. She earned a Bachelor of Arts and worked in the Criminal Division of the Legal Aid Society of Westchester County while pursuing her master’s degree in early childhood education at Manhattanville College. They married in 1970.
Joe did well in law school and said he knew if he were not blind, he would have received more than one job offer after graduation. He received many rejection letters, heard many excuses, and sometimes heard nothing at all after interviews.
Still, he almost did not interview for that one job offer; only after repeated urgings from different people, he did so and got the job at New York City’s Corporation Counsel’s Office, which already employed a blind lawyer in the Real Estate Tax Division.
Recounting his getting the job despite almost not interviewing, Joe invoked an ancient adage: “Luck is what happens when preparation meets opportunity,” words from Roman philosopher Seneca, reminding us that we make our own luck.
After three years of practicing tax law, Joe wanted to try something else, perhaps be a trial lawyer or a teacher. He and Alice drove out to Colorado where he planned to take the Colorado bar exam, but the day after they arrived, he was offered a teaching job at the University of Baltimore.
Before returning East, he and Alice goofed off and he learned how to ski, loving the feeling of freedom, and losing his fear of speeding down a mountain.
When they moved to Baltimore, Alice, who worked at the Baltimore Museum of Art, read for Joe from textbooks.
“Most importantly, from that time until I retired from teaching in 2007, she read all of my exams and papers to me.”
Getting a Confirmed CRB1 Genetic Diagnosis
Joe was diagnosed in his late 20s with retinitis pigmentosa (RP), but he thought it wasn’t correct for several reasons, including that people with RP lose peripheral vision and, in his case, he lost central vision.
Joe and Alice met Gordon and Lulie Gund while learning to ski at Snowmass in Colorado. The Gunds co-founded Foundation Fighting Blindness in 1971 to fund research for treatments and cures for blinding retinal diseases after Gordon was diagnosed with RP and ultimately lost his vision in 1970. He is a Foundation director and chairman emeritus.
In 1975, while in Baltimore, Joe received an LCA diagnosis from Dr. Irene Maumenee at Johns Hopkins’ Wilmer Eye Institute. After moving to Florida the next year, he began seeing a retinal specialist at Bascom Palmer Eye Institute in Miami.
Gordon came back into Joe’s life in the 1990s when he invited him to a Foundation dinner. There he met Iowa State University’s Edwin Stone, MD, PhD, who spoke of emerging research into gene therapy targeting a form of LCA and suggested Joe get genetically tested.
Joe’s genetic test showed his LCA was due do a mutation in his CRB1 gene, not the RPE65 gene, the focus of the research that led to the 2017 federal approval of LUXTURNA®, the first gene therapy for the eye or an inherited condition. People with LCA2 (RPE65) cannot make a protein needed by the retina to convert light into vision-enabling signals, which are sent to the brain. The breakthrough therapy involves injecting under the retina a human-engineered virus containing copies of a normal gene, so cells can express the protein.
In the CRB1 Research Update webinar, Joe said he was fortunate to have lived near a teaching hospital where he could learn about the cause of his blindness. In the Q&A, he asked where people with visual impairment should turn for help when living in rural areas with less accessibility to universities or large hospitals.
In answer, Ben Shaberman, Senior Director of Scientific Outreach and Community Engagement for the Foundation, said a team is working nationwide to educate eye-care professionals about LCA and other rare inherited retinal diseases (IRDs), so they can refer patients to specialists. He also encouraged people to email the Foundation at email@example.com for contacts in the academic and medical worlds of retinal specialists and researchers.
Laura Manfre, Sofia Sees Hope Co-Founder and President, said people can follow the Foundation and Sofia Sees Hope websites for information and research news. They also can email their questions and concerns to firstname.lastname@example.org.
She suggested people join the new CRB1 Network on Facebook and go to the Resources page on the Sofia Sees Hope website that has a link to a CRB1 group called Curing Retinal Blindness Foundation. Individuals also can find a strong Spanish-speaking community at Grupo CRB1 España y Latinoamérica.
As a lawyer, a law professor and a man diagnosed only a decade ago with CRB1, Joe said, “I’m not trying to paint an overly rosy picture of the challenges we face. I realize I am a minority, as I’ve been employed continuously from law school graduation to retirement. I also know with my class rank, I should have had more than just one job offer coming out of law school. At the same time, I realize that technology that was not available to me then has opened up many more opportunities for us …
“I guess what I’m trying to say is a child who is blind should be encouraged to develop interests in and to try activities, which, at first blush, might not seem suitable for a child with limited or no sight.”