The biotechnology company based in Boston and in Leiden, The Netherlands, announced earlier this month that it finished enrollment in its Phase 2/3 Illuminate study of sepofarsen for treatment of LCA10 due to the p.Cys998X mutation in the CEP290 gene.
LCA10 is a severe retinal dystrophy, causing blindness or severe visual impairment at birth or during the first months of life. The mutation affects about 2,000 people in the Western world.
Sepofarsen is an antisense oligonucleotide (AON) that works like “genetic tape” to fix the mutation. The therapy is unlike gene replacement therapies in which whole genes are delivered to replace defective copies.
The drug aims to repair the genetic defect that causes the disease in the ribonucleic acid (RNA). The mutation leads to an aberrant splicing of a person’s messenger RNA (mRNA) and leads to a non-functional CEP290 protein. Sepofarsen is designed to enable normal splicing, resulting in subsequent production of functional CEP290 protein.
Recruiting patients for clinical trials represents one of the biggest challenges in getting studies underway. The COVID-19 pandemic and concerns about spreading the virus presented an unprecedented challenge in and of itself. Pharmaceutical companies also have steered their focus from studies across the board as they raced toward developing and rolling out worldwide virus vaccines.
Finding the required 33 LCA10 individuals for the Illuminate trial in a subset of a people with a rare condition was exceptionally challenging, and ProQR exceeded that requirement by enrolling 36 participants.
During the Phase 2/3 study, the 36 patients, ages 8 and older, are set to receive sepofarsen either in a dose expected to be used once the drug gains approval or a lower dose or a placebo. The 12-month clinical trial is intended to support an application for marketing approval of sepofarsen. The study is being conducted in the United States, Canada, Brazil, The Netherlands, Belgium, France, Italy, Germany, and the United Kingdom.
Top-line results in early 2020 from the Phase 1/2 clinical trial of sepofarsen in 11 children and adults revealed that 60 percent of patients had improvements in visual acuity and navigating a mobility course. The study, carried out in the United States and Belgium, also netted a super responder, a person who responded particularly well to the treatment.
Laura Manfre, chair and co-founder of Hope in Focus (formally Sofia Sees Hope), said that as the parent of a child with an LCA diagnosis, she was told there was nothing that could be done and that her family needed to accept that their daughter would one day be blind.
“Now, in early clinical testing we have seen the potential for sepofarsen to make a significant difference for patients with LCA10 due to a mutation in the CEP290 gene,” she said. “We see hope for individuals living with this disease. We look forward to learning about the results of the Illuminate trial and continuing to work with ProQR as they advance their pipeline of RNA therapies to potentially help children, adults, and families who are affected by blindness caused by LCA and other rare inherited retinal diseases.”
Aniz Girach, MD, ProQR’s chief medical officer, said in a statement that the company was pleased to have completed enrollment of the Illuminate trial of sepofarsen.
“This marks an important milestone for ProQR, as well as for the LCA10 and broader inherited retinal disease community,” Girach said. “In surpassing our enrollment target, we were able to accommodate the broad interest to participate in the trial. This speaks to the fact that there are currently no approved treatments for patients with LCA10.
“If approved, sepofarsen has the potential to be the first therapy to address this high unmet medical need for patients who would otherwise face blindness, he said.
“We are grateful to those who have supported our efforts in bringing this trial forward, including our investigators, patients, and caregivers. We look forward to sharing the top-line results in the first half of 2022.”
Born with cerebral palsy (CP), Michael J. Kalberer grew up with a philosophy that has served him well throughout his 43 years.
“My parents raised me as an individual with a disability, not a disabled individual,” the native Long Islander recently said. “So, I never felt there was anything wrong with me or wrong with exploring something that could make things better. I didn’t feel like I had to be fixed and there’s a huge difference between those things.”
When Michael was about 10, he had difficulty with depth perception and felt sensitive to light.
“Sometimes a curb looked like a driveway, or vice versa,” when walking with his crutches.
Legally blind, Michael attributed his increasing lack of peripheral vision to CP and moved on.
After enduring an arduous transition from high school, he earned two degrees with honors: a bachelor’s in psychology and speech communications from Hofstra University and a master’s in social work from Adelphi University.
His vision dramatically worsened in his 30s. While at a New York Islanders hockey game, he looked at the scoreboard and suddenly it seemed like it was underwater.
His low-vision specialist referred him to a retinal doctor.
“He takes one look at my eyes and says, ‘Has anybody ever diagnosed you with a retinal disease?’ ”
The retinal specialist diagnosed him 10 years ago with Retinitis Pigmentosa (RP) , a group of related eye disorders that causes progressive vision loss as the retina’s light-sensing cells gradually deteriorate.
Michael said he was in shock when the doctor told him that he’ll permanently lose his sight, barring advancements, but advancements are coming.
Cataract surgery and then …
He underwent his first cataract surgery in 2012. He did more research and got involved with Foundation Fighting Blindness, where he served on a Foundation panel of doctors and described his experiences as a patient with visual impairment.
Listening to the doctor speaking before him, Michael could hardly sit still when he heard him delineate differences between Leber congenital amaurosis (LCA) and RP and realized his visual indicators aligned more strongly with LCA.
“Oh my God, oh my God, I gotta stop this guy,” he recalled saying after finishing his patient portion of the presentation. “Do not let him leave. We need to talk.”
Talk they did and two days later, he was genetically tested at New York’s Columbia Eye Clinic and received a confirmed diagnosis of LCA10, a mutation of the CEP290 gene, one of the more than 25 forms of gene mutations that cause LCA.
Since then, Michael has tracked LCA research advancements and his own experiences with his vision. He has 3 percent vision in one eye and 7 percent to 8 percent in the other. He can discern some shapes, colors and hand motions.
“I really took a hands-on, very proactive approach to navigating what my vision was like; I took control of logging, charting and tracking. It was kind of my way of taking control of the disease, so I had it and it didn’t have me.”
Michael Kalberer, left, with Katie van Benschoten of the Foundation Fighting Blindness.
He has also done fundraising for the Foundation, taking on leadership roles as a team captain for the organization’s VisionWalks and speaking at conferences.
“I can’t say enough about Foundation Fighting Blindness’s outreach and their confidence in my ability.”
Addressing the Foundation’s audience at its 2019 Dining in the Dark Spring Forward Fundraiser, he thanked the organization for helping him get a confirmed genetic diagnosis.
“The root of the Foundation for Fighting Blindness’s success is in cultivating relationships and helping change the way literally thousands of people with LCA and other (inherited rare diseases) IRDs view the world.
“How we process the world shapes who we are,” he told his audience.
Told he was ‘unemployable’
Michael also wrote an inspiring piece for the National Organization on Disability’s campaign to increase awareness of the professional ability possessed by individuals with disabilities.
Even though a career counselor once told him he was unemployable, he shared in his essay that he formed his own business called Michael J. Kalberer Presents. His company’s logo features a rising sun under the phrase “All Humanity Matters,” and he lists his roles as cultural competence presenter, communication etiquette specialist, transition planner, tutor and motivational speaker.
Michael’s life work now is educating people to maximize their personal strengths and to see others as more than their condition. He also has written an interdisciplinary curriculum to help professionals working with people with disabilities in diverse environments.
In the essay, he also described his work as a New York state licensed social worker at Family and Children’s Association, where he managed cases and helped people living with mental illness obtain and sustain employment in work environments conducive to success.
Michael attributes his feeling of empowerment to the unconditional support he continues to receive from his entire family and all his friends.
“My diagnosis of LCA could have altered the way they interact with me, but it’s made our relationships stronger. They are as emotionally invested in this journey as I am for myself, and there’s a beauty and a strength in the relationships that’s difficult to put into words.”
He did, however, capture the result of this supportive network of relationships in his closing sentence of that essay:
“I’m Michael J. Kalberer. I transcend cerebral palsy and Leber congenital amaurosis.”
Danielle Senick of Norwich, Conn., reached out to Hope in Focus (formally Sofia Sees Hope) more than three years ago when she needed answers about her deteriorating vision.
Doctors diagnosed Danielle at age 6 months with Leber congenital amaurosis (LCA), and her parents learned that this rare inherited retinal disease (IRD) would cause retinal degeneration to the point of having little or no vision.
She could see light and shadows, but she noticed a pronounced deterioration in her vision in her early 20s. We asked Danielle to talk about her experiences since she connected with us. Here is her story.
Danielle Senick, center, with her aunt Nancy (left) and mother Patty at the 2018 LCA Family Conference in Mystic, CT
“Though the (vision) changes were subtle, they caused me to realize how little I knew about my condition and I wanted to learn more. I did a little research and stumbled across Sofia Sees Hope. I was intrigued to hear about Sofia’s story, and I wanted to learn more, so I contacted the organization. I heard back, almost immediately, from Danielle Chiaraluce, who worked for the organization at the time.
“We had a lengthy conversation and she told me that she and Laura (Manfre, Co-Founder and Board Chair of Sofia Sees Hope) were interested to learn more about me, and they invited myself and a guest to Dinner in the Dark. I was honored to be invited, and it was a very fun, yet emotional, experience. It was wonderful to have my aunt learn a little bit about what my life is like to have no vision.
“At this event I met Laura, Sofia, Danielle, David Brint, his wife, Betsy, and his son, who also has LCA, and several other influential individuals. I was so honored during the auction to see how many people were willing to contribute their hard-earned money to the cause (including my aunt who bid on a trip to Bali).
Undergoing genetic testing
“Later I spoke with David and he helped me to get in touch with Spark Therapeutics, where I underwent free genetic testing. I had not seen a specialist or done anything about trying to learn about my diagnosis in several years because I often stumbled across roadblocks and it seems that the doctors that I previously had seen were not as educated about LCA. However, this experience was much different.
“I gave a blood sample and sent it to the lab and once my results came in, I spoke with Dr. Jill Harris in great detail about my results. She made me aware that my gene mutation is LCA-CRB1 (LCA8). Unlike LCA-RPE65 (LCA2), (for which there is a federally approved treatment), information about this mutation is still in the works. There is no cure, so I knew all along not to expect a cure and that with genetic testing you must be patient. I joined My Retina Tracker® (a Foundation Fighting Blindness free, secure online registry that helps connect families and enables researchers and doctors to track progress, prevalence and other variables of IRDs to move research forward) and receive emails about any new information on the condition and still remain hopeful.
“About a year later, through social media, I became connected with Kristen Steele of Iowa. (Kristen has LCA10 caused by a
Kristen Steele
mutation in her CEP290 gene.) She is a remarkable young woman who is extremely confident, well-spoken, and independent, and like me, a very passionate licensed massage therapist.
“When I spoke with her, I was in the process of attaining my license and still in school. I was having a little trouble getting the results from my license test in braille and she told me that was unacceptable and filled me in about her journey and how hard she had to fight to pave the way to get her testing accommodations. When I set up my accommodations with the testing center all I had to do was mention her name and request my accommodations and the center provided me with everything I needed.
“For that I am very thankful. I am now a licensed massage therapist myself and although we are both busy and haven’t talked in a while, Kristen is always available if I ever have any questions about my journey. I was fortunate enough to meet Kristen by attending the LCA Family Conference in 2019 (in Philadelphia). I also attended the family conference with my aunt and mother in 2018 in Mystic (Connecticut) and was quite intrigued by all the speakers.
LCA community welcomes Danielle
“At this conference I also met two individuals that are about my age who both have children with LCA. It was wonderful to meet with them and answer some of the questions that they had about what it was like growing up with LCA and any suggestions they had about being a parent of a child with LCA. As I have received so much guidance and help along the way, it’s wonderful to give back by helping others and giving them advice.
Deanna Carroll and Ashlyn Lincoln with their matching white cane tattoos.
“I have stayed in contact through social media and text messaging with these two individuals, Deanna Carroll and Ashlyn Lincoln, and have potential plans to go down to North Carolina and meet their children! I was able to meet up with them again in 2019 for the Philadelphia family conference. I brought my brother with me as a guest and he was also intrigued to learn so much about my condition.
“There was a plethora of informative speakers from all over the country, and it was amazing to see how far research had come even since 2018 at the last conference. I was especially intrigued to hear Tami’s story (Tami Morehouse, from Ohio, underwent RPE65 gene therapy as part of the LUXTURNA® treatment clinical trials) and how much it changed her life.
“I became quite emotional when she described all the little things that had come from it and changed her life, such as being able to go to her children’s socc
er games and cheer them on, actually being able to see them score goals, where before she had to rely on others to describe what was going on.
“The main takeaway from this process has been to continue to remain hopeful and stay involved. It is quite a process and the research is quite extensive and costly, so we would not have been able to come as far as we have without the generosity of others involved with Sofia Sees Hope.
“It’s amazing to see what a little bit of poking around on the Internet has led to and how much it has changed my life. My curiosity and doing a little bit of research to learn about LCA led to my becoming involved with Sofia Sees Hope, receiving genetic testing, attending wonderful events and conferences, and meeting truly amazing individuals, both sight-impaired and sighted.”
Building on her son’s love of music, singing, moving, and reading, Laura Steinbusch created a multilingual children’s songbook called Lux+Louiseto help youngsters learn music by braille.
With songs in Dutch, English, French and German, the songbook’s characters, Lux the lizard and Louise the mouse, help expose children with blindness or visual impairment to learning other languages from an early age and allow them to independently explore the world.
Laura came up with the idea because her son, Enzo, now 6, easily learned new words early on through songs in French or English, especially when he already knew them in Dutch.
Enzo was born in 2014 in Lausanne, Switzerland, and genetically diagnosed at 18 months with LCA10-CEP290, a form of Leber congenital amaurosis causing severe retinal dystrophy because of mutations in the CEP290 gene. Enzo lives in The Netherlands with his mom and his dad, Merlijn, and his new little sister, Maud.
He started to learn braille when he was 5 and he enjoys it a lot, his mom said.
“His favorite story is ‘the story of the little mole who knew it was none of his business,’ which we had to buy in the four
Enzo and his mom Laura at an Austrian playground listening to sounds from a cowbell glockenspiel.
languages of my songbook because he wants to know the whole story in those four languages.”
Lux+Louise contains five popular children’s songs with printing in black and in braille and six visual and tactile illustrations with explanations and questions. Along with singing about a bus and a spider, the book helps with learning body parts and movement.
“This makes it easier for blind children to connect the song texts to the tactile illustrations and the real world,” Laura said. The songs can also be played on the piano or flute.
“Most children adore singing; some children even sing before they speak,” she said. “Blind or visually impaired children use their hearing all the time and mostly enjoy music and making noise … Independence is also important for learning music. It would be best if blind children could learn reading braille music as soon as they have learned to read braille text.”
The songs are: “A Ram Sam Sam,” “Head Shoulders Knees and Toes,” “Are You Sleeping (Brother John)?” “The Wheels on the Bus,” and “Itsy Bitsy Spider.”
“I hope people enjoy learning another language through music and learn to read music braille,” Laura said. “In the end, I hope it helps blind kids explore the technical world on their own.”
Since its launch in March 2018, breakthrough gene therapy LUXTURNA®™ continues to be successful in helping improve vision in people with inherited retinal disease due to mutations in both copies of the RPE65 gene and viable retinal cells as determined by a healthcare professional. The therapy treats LCA2, known as LCA/RPE65, one of more than 25 forms of Leber congenital amaurosis.
The drug – developed by Spark Therapeutics and a team of retinal research superstars that included Dr. Katherine A. High and Dr. Jean Bennett – came to fruition after 12 years of research and millions of dollars in investment.
Spark Therapeutics could not comment on the number of people who have received the gene therapy, but spokesman Kevin Giordano recently said the company has shipped well over 200 vials of the therapy since the U.S. Food & Drug Administration approval in December 2017. One vial of the drug treats one eye.
Trained retinal surgeons at one of the 10 eligible treatment centers in the United States deliver the gene therapy to the back of the eye by subretinal injection using a needle the size of an eyelash; about a week or so later, the patient undergoes the procedure in the other eye.
“Spark Therapeutics is thrilled patients continue to benefit from LUXTURNA (voretigene neparvovec-ryzl),” Giordano, Spark’s External and Product Communications Lead, said. “A gene therapy is a major milestone, not only for those of us at Spark, but also for the patient community and broader gene therapy field.”
The cost of the drug – $425,000 for each eye – initially caused anxiety among patient families, but Giordano had good news about insurance coverage.
“Payer coverage has exceeded expectations, and to our knowledge no treatment-eligible patient has been denied treatment due to their insurance coverage,” he said.
LUXTURNA also is being used beyond this country through license and supply agreements with Novartis, which has the rights to commercialize the drug in Europe and all other markets outside the United States. Spark manufactures and supplies the gene therapy to Novartis, according to Giordano.
Also, results from ongoing studies continue to support the drug’s safety profile and efficacy.
“In 2019, Spark presented four-year durability data from the LUXTURNA Phase 3 clinical trial,” Giordano said.
“We closely watched the clinical trials and the FDA approval process for seven years, starting when Hannah was diagnosed with LCA/RPE65 at just a few months of age,” Amy said. “Seven years of hope.
“Two years out from Hannah’s surgery, I can say we feel grateful and fortunate that she was treated with LUXTURNA. No regrets. LUXTURNA was hope realized. It delivered what it promised.”
She said what that has meant for Hannah has been nothing short of life changing.
“It has given her more independence, which has been wonderful for her self-confidence. It has given her the ability to see what she couldn’t before.”
Since the surgery, Hannah’s vision in dim lighting and her visual acuity improved. She is now 9 and just finished third grade.
Sometimes, her mom said, it’s the little things that are the most amazing.
“A year after the surgery, she was about to eat hot oatmeal and said, ‘Hey, I see steam. Hey, I can see that,’ ” Amy said.
“There are still things that pop up that she’s seen for the first time, like when she said, ‘Mom, did you know there’s a pattern on this toy?’ It’s fun to see her discovering.”
Amy said she and her family will be forever grateful to Dr. Bennett.
“There has been a lot of talk about heroes recently and Dr. Bennett is our hero. We are grateful for this groundbreaking treatment that she developed, that has been life-changing, not only for our daughter, but also for the sons and daughters and loved ones of so many others as well.”
His mom, Sarah St. Pierre Schroeder, told us that her now-11-year-old is doing amazing and only occasionally has issues with dim lights, “but nothing like before.”
Their days in Mount Dora, Fla., have changed in a major way.
“He still starts his day with his trusty smoothie and waffle, but after that, Creed wants to create new pranks (today was putting ice in the tub). He said it was nice and warm so I could soak my feet.”
Creed Pettit
Creed now loves to play board games – Trouble, Sorry, Battleship and Uno.
“His vision has changed everything. He can manipulate small objects, he is using pointer fingers, and loves trying to roll his eyes in the mirror.”
Creed still likes to draw, and he loves riding and popping wheelies on his bike named Carlitos. He also likes to talk.
“Talking more is an understatement! Sunup to sundown, he is talking. He has also learned how fun it is to use his imagination, something he never did before. He creates awesome stories during this time. He is so much more independent; I have to remind myself of that often.”
At first, she and her husband, Chad, could see that Creed’s vision improved some, but once he became confident about his gene replacement, they noticed him finding toys and games.
“He was suddenly enjoying things he didn’t before. He now expresses when he can’t see. Yesterday it rained all day, I kept waiting for him to tell me it was too dark inside, but he was fine. He just started doing staring contests. I love looking at his eyes during the contest.”
Sarah said she is incredibly grateful.
“Creed’s surgery is something we still thank God, St. Raphael, St. Lucy and Sister Miriam Teresa, for every night.”
Like many kids across the country, Creed finished school at home because of the coronavirus pandemic. He graduated from fifth grade and thought because he finished school at home, he wouldn’t have to wear the graduation cap.
“But I was not going to let that slide,” his mom said. “I made one and took pictures.”
Anxiety, and a Friend to Call On
Throughout his journey, though, Creed felt anxious, something Sarah had learned that might happen when, before Creed’s surgery, she talked with Tami Morehouse, a LUXTURNA clinical trial participant at age 44.
Tami, a Sofia Sees Hope Ambassador, tries to calm fears and advises potential gene therapy patients and their parents that even though undergoing the surgery has the potential to do such good by improving vision, they should think about their expectations, especially with children.
“We are comfortable in our own zone; give us a little bit of change and it can throw us off,” Tami said.
Sarah understands.
“He started to have a lot of anxiety. He had a hard time sleeping. I feel everything changed so fast that he was overwhelmed, but we have worked hard on getting past that.”
Sarah and her family are in a great place now. But after they were home from the hospital in Miami and settled into their routine, she said she became very emotional.
“All the tears I had held in for nine years started to come out. I felt I no longer had a purpose; I was so used to staying busy. I did not know who I was supposed to be.”
She got some help and realized she still was needed because people need her help learning about and understanding this groundbreaking gene therapy.
“I still find myself shocked over how this has changed Creed’s life and so many other lives.”
Kristen Steele knows a thing or two about telling her story and getting what she needs to be her best.
The 22-year-old from Council Bluffs, Iowa, is a licensed massage therapist in Iowa and Nebraska. She travels throughout rural Nebraska, giving massages to the elderly and the ill as an independent contractor specializing in geriatric care.
But she had to fight to take her massage therapy exam in Braille. Never had anyone taken the Massage and Bodywork Licensing Examination, known as the MBLEx, in Braille.
Kristen told her story to people living with Leber congenital amaurosis and other inherited retinal diseases (IRDs) at the Hope in Focus (formally Sofia Sees Hope) second LCA Family Conference in Philadelphia in July. The gathering brought together patients, advocates, doctors, researchers and biotechnology leaders – more than 80 people from across the nation and Mexico. She spoke from the audience following the conference’s session on patient advocacy called “Your Voice Matters!”
Doctors diagnosed Kristen with LCA as an infant, while her clinical diagnosis of LCA10 (CEP290) came years later in middle school. She learned Braille at age 3.
Kristen planned to be an English teacher but decided her passions aligned more with the medical field. She enrolled in Midwest School of Massage near Omaha after rejecting another school because of difficulty accessing its curricula. At Midwest, she found an instructor with a background in exercise physiology and physical therapy. She said the teacher cared and put in extra time to make sure she fully understood the techniques.
After completing the 1,000-hour massage therapy course on anatomy, physiology and pathology, plus 200 practice massages, with a 4.0 average, Kristen learned she couldn’t take the exam in Braille. Instead, volunteer readers administered the test to people with visual impairment. Readers could be unfamiliar with and prone to mispronouncing complex anatomical and medical terms, putting Kristen at risk of failing the exam. Plus, she didn’t want to pay the $195 exam fee twice.
She found a blind lawyer in Iowa and they sued the Federation of State Massage Therapy Boards. She reached a settlement agreement and took the exam, passing on her first try. Kristen also insisted on having a professional reader, an occupational therapist familiar with terminology used in the test questions – just in case she needed clarification.
Kristen polished her resumé with the help of visual interpreter services, highlighting her certificates in advanced dementia processes and other therapies.
“It placed my disability on the back burner, and it gave me the upper hand when you have sighted massage therapists and they’re interviewing without any of these advanced certificates,” she said.
A company interviewed Kristen by phone last year and hired her the day after her in-person interview. She continues to thrive there as a massage therapist specializing in geriatric care. She also devised her own transportation system to get to and from clients in the Nebraska countryside.
Kristen paved the way for others, including perhaps another conference attendee, Danielle Senick from Norwich, Conn. Danielle is studying to be a massage therapist, and Kristen said she will be there to help her succeed in changing the rules to take the exam in Braille in Connecticut.
The 21-year-old paved a smoother road for those without vision by changing massage-therapy exam protocol, writing policies and procedures, and proving herself as a competent, independent contractor who makes house calls to the elderly and the ill in rural Nebraska.
Kristen, who lives in Council Bluffs, Iowa, near the Nebraska line, forges through life with passionate determination. She finds the support she needs to be her best and passes her knowledge along so others can be their best.
Kristen Steele proudly shows off her massage therapy certificate.
She has helped those without vision to pursue massage therapy careers, including Connecticut resident Danielle Senick. They connected through a Facebook page for people with Leber congenital amaurosis (LCA) and soon will connect in person at the second LCA Family Conference presented by Hope in Focus (formally Sofia Sees Hope) in Philadelphia this weekend, Friday, July 26, to Sunday, July 28.
Kristen, Danielle and those living with LCA or other rare inherited retinal diseases (IRDs) will gather at the conference, which offers myriad opportunities to engage in thoughtful and interactive exchanges of knowledge, ideas and viewpoints on research, future treatments, advocacy, and people sharing their stories.
Diagnosis: LCA10
Doctors diagnosed Kristen with LCA as an infant, although her clinical diagnosis of LCA-CEP290, also known as LCA10, came years later in middle school.
She began reading Braille at age 3, and since first grade, has used a BrailleNote, a mini tablet-sized personal digital assistant with input through a Braille keyboard.
Struggling in school and having trouble with teachers adapting to a blind student, Kristen’s mother quit her job in the accounts receivable department at a medical supply company.
Her mom would pull up her assignments on the computer and tell her what she was missing and what she needed to go forward with the work.
“I had straight As but it was hard to find someone competent enough and willing to adapt,” Kristen said. “My mom, still to this day, is in LCA groups with parents of blind children. She still tries to help out other families and reconnect and advocate.”
A friend of her pharmacist-dad helped her with geometry and algebra by making 3-D shapes with rubber bands, detail that enabled her to visualize and understand the problems.
“That worked. It was just the extra time and energy,” Kristen said. “I didn’t let anything stop me. Sometimes I’d be up ’til midnight doing papers. I spent countless hours. I had to do it because I couldn’t let myself fall behind because of someone’s ill-preparedness.”
Kristen graduated ahead of her class in December 2014, with plans to become a high school English teacher. That changed during a semester at the University of Nebraska at Omaha, where a public-speaking assignment to interview a person in her chosen field led to a blind English teacher in Indiana.
“She did a really great interview, but she told me to think twice about it.”
Working from 6 a.m. to midnight, it took double time to grade papers. The teacher, then 48 and named Teacher of the Year, said she’d never married or had children because her job took over her life.
“She also mentioned she has a lot of students texting in class, throwing spitballs. They threw a backpack at the window, broke the window, and they were laughing, thinking they played a cool prank on her.”
Choosing her path and fighting her fight
Kristen decided her passions aligned more with the medical field, given her parents’ work, and her interest in the healing arts. Also, her grandmother, who had dementia, had recently died, and she thought more about geriatrics and helping the elderly.
She reached out to a blind friend who is a licensed massage therapist and researched massage therapy schools, finding and rejecting one because of the difficulty in accessing its curricula. She ultimately enrolled at Midwest School of Massage near Omaha. The school turned out to be a perfect fit, pairing Kristen with an instructor named Les Lundberg, who had a background in exercise physiology and physical therapy.
“He cared. He wanted to put in the extra time to make sure I had a quality experience.”
Using a skeleton as tall as Kristen, her teacher went over each of the body systems and muscles, reviewing each individually on the skeleton, on herself and then on the instructor to make sure she understood the techniques.
“It was a really nice blend of anatomy and physiology.”
After completing the 1,000-hour course in February 2017 on anatomy, physiology and pathology, plus 200 practice massages, with a 4.0 grade point average, she studied for the Massage and Bodywork Licensing Examination, known as the MBLEx.
Before taking the exam, Kristen took on the Federation of State Massage Therapy Boards because it would not administer the test in Braille. She would have to take the four-hour test with a hundred multiple-choice questions using a human reader, a volunteer likely unfamiliar with medical terms.
“The exam cost $195 and I didn’t want to pay the price more than once and I didn’t want to fail.”
Through the National Federation for the Blind, Kristen found a blind lawyer in Iowa and they sued the Federation of State Massage Therapy Boards.
Eight months later, they reached a settlement agreement, making Kristen the first to advocate for and pass the MBLEx in Braille.
“I took the exam and passed on the first try, but I was debating over this whole time, was it worth it? I could have been licensed and working.”
In the end, she knew it was worth it.
“I wanted to create this advocacy for anyone else pursuing massage therapy and let the boards know it should be in Braille.”
Kristen now works with others, including Danielle, who was diagnosed with LCA-CRB1, also known as LCA8, and who is finishing massage therapy school and getting ready for the MBLEx.
First steps down a career path
Massage therapists often work as independent contractors and Kristen’s first contracted job led her to a brand-new company.
“They were accepting and very welcoming at first,” she said.
She honed her massage therapy technique on a hospice patient with dementia. The patient essentially was non-verbal, meaning Kristen learned the woman’s massage therapy needs from her client’s physical responses. The woman also could not hear well and indicated her soreness by holding out her arthritic hands and feet.
“If they can’t form words, I need to pay attention to what they are doing and how they’re reacting.”
Her next client did not have dementia and could tell Kristen where she had pain on her shoulders and back from bedrest.
“She helped me with the verbal side of crafting my technique.”
Kristen also wrote the company’s new policies and procedures for its massage therapy program.
Her employer, while pleased with her job performance, tried to have her sign a written contract that she couldn’t read because it wasn’t in Braille. Her mother came with her to read the new contract, but the company initially did not produce it.
“They finally spilled it. ‘We need to lower your rates.’ ”
She brought the case to the Nebraska Department of Labor and told officials she never looked over the contract because she can’t see.
“That went south quick. We won.”
She applied for a job at another company.
“The interview went OK. They just didn’t believe in me, that I would be able to find transportation, find the patients. They didn’t have the confidence that the blind could do it.”
She took a job at a physical therapy clinic in Council Bluffs but left because of few hours and low pay.
Kristen also began accumulating Continuing Education Unit (CEU) hours to help her stand out as a job candidate in a field of sighted massage therapists.
Comfort Touch™ instructor and licensed massage therapist Mary Kathleen Rose never had a Braille reader, so her course materials were not available to read by Braille.
Kristen ordered a print copy through Bookshare.org, an online library for people with visual disabilities. Bookshare scanned the book on a Monday and uploaded it by Friday, and she began the class.
“I was the first one to put these materials into Braille that are sold on Amazon and everywhere throughout the country. … That was the first ever CEU class that I took, and it was really cool because Mary Rose did a video of me reading in Braille the Comfort Touch™ textbook. I had adapted these course materials and paved the way, and for my turn (on the video) she wanted me to read ‘Adapting to Change,’” which deals with loss, aging and change.
In a 2017 North America/Caribbean Region Onkyo Braille Essay Contest, in which Kristen placed second, she detailed her advocacy for Braille in a piece called “Shining Through Darkness.” She recalled in the essay her Comfort Touch™ teacher saying after hearing her read: “Your reading . . . it’s just like everyone else.”
She also wrote in the essay: “Remaining literate despite being blind is not difficult; consistent practice can equal or surpass the fluency of print readers with eloquence and grace.”
Expanding her personal and professional horizons
Kristen also earned certificates in hot-and-cold stone therapy, aromatherapy, Reflexology, advanced dementia processes, and she is a licensed massage therapist in Iowa and Nebraska.
She familiarized herself with Aira and Seeing IA, visual interpreter services. She sent her resumé to Aira and worked with a trained professional who formatted and polished her draft into what Kristen called the perfect resumé.
“It placed my disability on the back burner, and it gave me the upper hand when you have sighted massage therapists and they’re interviewing without any of these advanced certificates.”
Between her resumé and an initial phone interview, Kristen felt she would be judged equally as a sighted person before showing up for an in-person interview.
After seeing a familiar job posting in May 2018, she sent her resumé to the company where representatives a year earlier did not believe she could do the job. She received a call back in an hour and did a phone interview.
During her in-person interview, Kristen demonstrated Aira – using a phone and wearing glasses connected via Bluetooth to a hotspot – and called an agent, displaying her ability to navigate a client in-take process and get around the office. Or, as she said, “I took Aira for a spin. I walked around the office, read people’s name tags, saw suite numbers.”
The company hired her the next day and she’s currently thriving there as a massage therapist specializing in geriatric care.
As an independent contractor, Kristen travels to clients and returns using a door-to-door shuttle service. Initially her mom helped, then she used Lyft and Uber, but that became expensive, prompting her to develop her own transportation service, which she jokingly calls Kristen’s Transportation Fleet. She contracts with drivers who get her to clients based on a negotiated fee.
So, what does this 22-year-old do when she’s not busy working and enhancing her skills?
She loves working and playing with her beautiful guide dog, a golden retriever named Corvette.
She loves to shop at a gigantic mall billed as the largest shopping area in Iowa.
“I like reading. I’d like to write a non-fiction book, kind of a memoir someday about my life and my work with comfort care.”
And she drives.
“I like to drive. My mom sits in the passenger’s seat. We go on the back roads. It’s so freeing.”
As Kristen said, quoting Helen Keller in her reading for the “Adapting to Change” video:
“What we have once enjoyed, we can never lose. All we love deeply becomes a part of us.”
The best of both worlds – that’s how Ashlyn Lincoln describes life with her two sons: 4-year-old Gunner, who was born without vision, and 7-year-old Ace, who is sighted.
“Both Ace and Gunner teach us many life lessons, regardless of who is sighted and who is blind,” says their 29-year-old mom.
7-year-old Ace and his 4-year-old brother Gunner. Gunner was diagnosed at 6 months with LCA10, caused by a mutation in his CEP290 gene. Doctors determined Gunner came into this world with no usable vision cells and no light perception.
Living in eastern Iowa, Ashlyn and her husband, Axel, noticed problems with Gunner’s eyes in August 2014, when he was about 2 weeks old: he stayed awake during the day and his eyes would not focus. The pediatrician examining their infant at 6 weeks wasn’t concerned, but to put them at ease, he referred them to the first in what would become a series of specialists, leading to lots of tests on Gunner’s eyes and on his parents’ genetic backgrounds.
Gunner was diagnosed with Leber congenital amaurosis (LCA) at 4 months; at 6 months in February 2015, his parents learned through genetic testing that he had LCA10, caused by a mutation in his CEP290 gene. Doctors determined Gunner came into this world with no usable vision cells and no light perception.
Last May, the family moved to a suburb of Nashville, seeking a stronger support system and better resources for Gunner, who is now thriving at the Tennessee School for the Blind.
Mr. Independent
Gunner loves prekindergarten, especially gym time and swimming lessons. He listens to try to understand musical instruments, and he loves making art and writing on the Brailler. “He’s pretty independent,” Ashlyn says.
Ace and Gunner have a typical sibling relationship, blaming each other, kicking each other, playing in their own world, she says. “Ace pretty much treats him like he is sighted. He adjusts (when he remembers Gunner cannot see) and goes right back to thinking it. It’s the best of both worlds.
“Their positive outlook and attitudes on life really help us be better ourselves. I just feel so lucky to be able to always have different outlooks on everything that others may not realize,” she said.
Gunner ‘reads’ his Braille books. Gunner’s reading is feeling the Braille but making up his own stories as he goes along.
Their daily life is like other families — the boys get up and get ready for school, eat breakfast, brush their teeth. After school they have snack, play, watch cartoons, do homework.
“This might be the only thing ‘different,’” Ashlyn notes “Ace’s homework is reading, so Gunner will bring his Braille books to the couch and ‘read’ them, too. Gunner’s reading is feeling the Braille but making up his own stories as he goes, which are usually pretty creative and cute.”
Ashlyn’s best-of-both-worlds might as well extend to a third “world,” given the influence, support, and love she and her family have received from Axel’s “battle buddies” from his time in the Marines.
War Wounds Inside and Out
Axel served four years’ active duty (followed by four years’ inactive duty), being deployed twice to Afghanistan and once to Haiti on a relief mission.
He came home from Afghanistan suffering from severe injuries when his right shoulder took the brunt of his Humvee’s impact after it ran over an IED, an improvised explosive device.
Axel and Ashlyn married as soon as they could after his return home. He has a 90 percent disability rating for the injury and for Post-Traumatic Stress Disorder (PTSD). About two years ago, Alex’s service dog, Tucker, became part of the family, helping with his PTSD and bringing comfort when his anxiety is high. Tucker’s also great with the boys and may someday be joined by a service dog for Gunner.
Axel wasn’t the only one to come home to the Lincoln family. The Marines came, too, and they are still part of it.
When Ashlyn was about to deliver her firstborn, her husband and his Marine friends were there. If the baby was a girl, she’d get to name her. If not, Daddy and his buddies had the honors.
“They gave me options. I had Achilles, Leonidas, Thor, Zeus – I was excited about that one.”
Achilles it was, or Ace, as they call their now first-grader.
It was Ashlyn’s turn to name their second boy, but she still wanted to honor their military family.
She explained that a gunner, sitting on top of a Humvee and rotating 360 degrees to protect its occupants, would throw himself on a badly injured compatriot as “an unwritten act of brotherhood.” The gunner in Axel’s case did not have to, but if Axel’s injuries were worse, he would have.
“So, to go along with the history of Ace’s name, we picked Gunner to name him.”
When she picked the name, she didn’t think much about looking up its meaning.
“Later on, after we got the diagnosis, I randomly decided to look up the meaning to find it meant ‘Battle Strong,’ which seems very appropriate on our adventure.”
You’re Overwhelmed and It’s OK
Life wasn’t always easy though. Dealing with Gunner’s diagnosis and coping with new realities was difficult. Here is the message she would like to extend to other mothers: “I was overwhelmed, and I was tired. I want to acknowledge that I know you’re overwhelmed and it’s OK.
“Take baby steps, know your local resources, and know that it’s not just something you’re going to conquer in one day.”
For support and to learn more about the LCA community, Ashlyn and a friend she met through an LCA Facebook group, traveled to Connecticut last fall to attend Hope in Focus (formally Sofia Sees Hope) LCA Family Conference, where she found a sense of community.
“It was fantastic,” she says. “There are families in other states and I’m not alone and here we are together. It’s just a moment where you can find comfort and know you’re not alone.”
Ashlyn said she does have a personal goal – one that she’s fulfilled right here.
“It’s hard to admit when your child is born and not perfect, and your husband has PTSD,” she said. “I hope that just by telling my story about LCA and veterans, that other families also can not feel so alone.”
The lack of information on rare diseases can create difficulty in developing drugs to treat them. To help, it is important to study the natural history of rare diseases.
Compared with common diseases, researchers know little about rare disease signs and symptoms, how the disease changes over time, and ways in which the disease affects the lives of patients and their families.
Natural History studies track the course of a patient’s disease over time. They identify demographic, genetic, environmental, and other variables that shape the drug development process
Dr. Eric Pierce, Massachusetts Eye and Ear
“In general, Natural History studies can be helpful precursors to clinical trials of potential treatments for inherited retinal degenerations for multiple reasons,” said Eric A. Pierce, MD, Ph.D., with Massachusetts Eye and Ear. “For example, they can help identify the tests or measurements which would be most appropriate to use as endpoints in therapeutic studies.”
Another way to view such studies is to “Begin with the end in mind,” as suggested by Anne R. Pariser, MD, in her work on Natural History studies for the U.S. Food and Drug Administration
Natural History data provide knowledge and an independent understanding of a disease, while establishing an essential foundation for building drug development programs. These studies have been characterized as the “pillar of epidemiologic research on rare conditions,” and, along with assisting in developing drugs, they help with patient care, best practices, research priorities, and clinical trial readiness, according to Dr. Pariser, director of the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences.
The studies give scientists and researchers a better estimate of the prevalence of the disease, help identify potential biomarkers, affect clinical outcome assessments, and determine the feasibility of established assessments for clinical trials.
A rare disease is a disease or a condition that affects fewer than 200,000 Americans. With a relatively small number of people affected by the 7,000 diseases considered rare, scientists sometimes face daunting odds in finding enough people meeting study requirements.
In the Leber congenital amaurosis (LCA) community, scientists are looking for people to take part in different stages of drug development.
Editas Medicine, a genome-editing company based in Cambridge, Mass., is sponsoring a Natural History study of LCA10, known by its gene name CEP290, to inform the design of potential future treatment studies involving genome editing in LCA10. The purpose of the study is to understand and better describe the clinical course of LCA10-related retinal degeneration that is associated with a particular genetic change in the CEP290 gene called c.2991+1655A<G.
The study will be used to characterize the range of visual function in patients, evaluate which visual tests may be most useful, and determine the rate of change in visual function over a one-year period.
Dr. Pierce, director of the Ocular Genomics Institute and the William F. Chatlos Professor of Ophthalmology at Massachusetts Eye and Ear (MEE) and Harvard Medical School, is the principal investigator at one of the seven sites in the United States and Europe actively recruiting patients for this Natural History study. For more information, call MEE at 617-573-6060 or visit www.enlightenLCA10study.com/. Study details also can be found at ClinicalTrials.gov Identifier: NCT03396042.
The two groups of conditions below describe the parameters for taking part in the study. Taken together, they illustrate the potential difficulty in finding the 40 participants needed for the study of this rare disease.
Patients must meet six conditions, known as inclusion criteria:
3 years of age or older;
Abnormally decreased vision, with examination and test results consistent with inherited retinal degeneration due to mutations in the CEP290 gene;
Able to cooperate with assessments relative to the patient’s age;
Clear ocular media and adequate pupil dilation in at least one eye to permit good-quality examination of the interior surface of the eye opposite the lens and optical coherence tomography (OCT) imaging;
Able to successfully navigate a mobility maze at a level of difficulty below the maximum performance level.
Patients cannot participant if one or more of the five following conditions, called exclusion criteria, exist:
Visual acuity of no light perception in both eyes;
History or current evidence of a range of medical conditions that may preclude attending scheduled study visits, safe participation in the study, or affect the study results;
History or current evidence of ocular disease in either eye that may confound assessment of this inherited retinal disease;
Currently receiving gene therapy and/or has received gene therapy;
Currently enrolled in an investigational or interventional drug or device study and /or has participated in such a study within 30 days of screening.
Participants currently are being recruited for a Foundation-funded Natural History study of disease progression in patients with USH2A-related retinal degeneration associated with congenital hearing loss (Usher syndrome type2a) or non-syndromic retinitis pigmentosa (RP39).
Annie Cohane takes singing lessons and piano lessons, she runs track, she’s working on swimming, and she’s a second-grader at an elementary school in Norwell, Mass.
She’s 8 years old and an emerging Braille reader.
“She’s a happy, very happy-go-lucky, strong-willed, little girl,” Annie’s mom, Jenny, said.
The goal for Jenny and her husband, Kevin, is for Annie to become as independent as possible.
She rides the bus to school, she goes on play dates.
Annie was diagnosed with Leber congenital amaurosis (LCA) at 3 months of age. Genetic testing later showed a mutation in her CEP290 gene.
“She just figured out she was blind in the last few years,” Jenny recently said. “So far, it turns out it doesn’t affect her at all.”
In 2009 when Annie was 2 months old, she involuntarily moved her eyes side to side, prompting a diagnosis of nystagmus, a condition affecting about 24 out of 10,000 children.
“I was shocked,” Kevin said. “I probably didn’t take a breath for 50, 90 seconds, trying to figure out what that meant. You never imagined your child would be anything but happy and healthy.”
Genetic testing later showed a mutation in her CEP290 gene.
The Cohanes had hope, however, because doctors assured them that cures and treatments were in the pipeline to help people like Annie with LCA.
Barely wrapping their heads around the life-changing news, they needed to tell their families. Jenny already had moved onto the planning side of caring for Annie, while Kevin made calls to family and friends.
“We were only concerned about Annie,” Kevin said. “They were concerned about Annie and us.”
While still processing the news, Jenny and Kevin – who met while training for triathlons, literally and figuratively crossing each other’s paths – got busy.
Early intervention specialists came to the house weekly, and then Annie enrolled in an infant/toddler program at the Perkins School for the Blind until she was 3. They worked to ensure their little girl’s access to any available resources to help her become confident and independent – just like any other child.
Clearly these specialists – social workers, occupational therapists, vision specialists, physical therapist, speech therapists – helped Jenny and Kevin navigate this unfamiliar world with Annie and her older brother, Petey.
Then, these endurance athletes, who happen to have fund-raising experience, decided after attending Foundation for Retinal Research conferences to help fund research into LCA.
Jenny came up with the idea of giving parents a nice night out, and in 2012, they turned their backyard into a big fund-raising party with plenty of donated food, drink and live music.
The parties, each with a theme, became a platform for learning from Annie. They chose themes in which partygoers could take away their experience and apply it to their lives. They ranged from stop-and-smell-the-rosemary to back-to-basics.
“That is how we try to live our life,” Jenny said.
Two years ago, 350 people came to their barn and backyard. This past September, they raised more than $37,000, bringing their total over the years to more than $160,000. They originally gave the funds to the Foundation for Retinal Research, and now they go to the Foundation Fighting Blindness since the FRR rolled into the FFB. Also, this year more than $2,400 went to New England Adaptive Sports.
Attending this year’s Dinner in the Dark presented by Sofia Sees Hope also gave the Cohanes hope. At the event, Jenny and Kevin sat next to Jack McCormick and his 5-year-old lab/golden-mix guide dog, Jake. Jack is a 20-year-old business honors student in Ontario, Canada. He also is a thoughtful, well-spoken advocate for accessibility, and he is a mentor, urging people with LCA to tell their stories to boost self-confidence and attract researchers.
“He was phenomenal,” Jenny said. “He’s exactly what I want Annie to be.”
Eight years ago when Kevin came home after getting Annie’s diagnosis, he took a nap, and when he woke up, he told Jenny he had a dream that Annie was sitting across from him in a hospital room.
“She was 13, 14, and I could tell she could see me, and I started crying, and she said, ‘Dad, why are you crying?’”
He told her, “I’m just so happy that you can finally see what we look like.”
She replied: “But I’ve known what you looked like all along.’’
Kevin believed then, as he does now, that his dream foreshadows a time when researchers find a cure for LCA-CEP290 and Annie will see.
In October, the FDA recommended approval for genetic therapy for the LCA-RPE65 gene, one of more than 25 genes associated with LCA. If approved, the therapy would be the first of its kind for LCA and the first in the nation for any genetic disease. Also, the research in progress when Annie was an infant is now well into later stages of study.
Kevin said after the dream he felt an amazing sense of peace.
“I just felt confident we’d be able to get through it, even if we didn’t know what we were facing, he said. “All we have to do is love her to our best ability and everything is going to be fine in the end.”
