Lou and Terry Jo’s story

An elusive diagnosis

When her son Louie (Lou) was born, Terry Jo already had four daughters, including a set of identical twins. As a nurse-midwife, she learned while working in Nigeria, where more twins are born than in any other country, that the child born after twins carries big luck. So, she and her husband thought they would try for a boy and were thrilled when he was born. Little did they know their lucky baby had something unlucky lurking in every neuron in his brain.

Lou was a cuddly and adorable baby, but his mother sensed he was different from her other children. When he turned one year old and was still unable to sit up or crawl, a neurologist diagnosed him with cerebral palsy. With a diagnosis that did not seem right, Terry Jo and her husband, Dave, flipped through medical text books, stumbling upon a page about Angelman syndrome (AS). Lou looked a lot like the people in the photos, but it was hard to believe that he was severely cognitively disabled.

The family made an appointment with Dr. Ken Lyons Jones, who happened to be the author of their medical textbook. He looked at cheerful little Lou, who was not meeting his milestones, had a tremulousness about his movements, and he took his tuning fork and placed it on Lou’s knee. Lou laughed hysterically—one of the hallmark symptoms of AS. After a blood test, the diagnosis was confirmed.

People with AS are unable to speak and are dependent on others 24 hours a day. Many have intractable seizures and are unable to sleep. It is an incurable, rare disease, and a devastating diagnosis.

A tireless search for answers

Dissatisfied with the lack of treatment options for AS, Terry Jo and Dave scoured scientific and medical literature written about AS, determined to become experts in UBE3A, the maternal gene that Lou was missing. UBE3A is a ubiquitin ligase, which targets proteins for destruction in the cellular recycling center. Terry Jo and Dave learned that Lou was missing UBE3A in every neuron in his brain, which meant that Lou would remain unable to speak, unable to sleep, and possibly unable to walk or feed himself for the rest of his life. Feeling helpless, Terry Jo booked a flight for her and Lou to attend the first international AS meeting in Finland.

During her travels, she met Dr. Arthur Beaudet, a geneticist, who had discovered the gene for AS. He firmly believed it to be a curable disorder since AS occurs when there’s a problem on the mother’s chromosome while the paternal gene is perfectly fine, it’s just silenced. Dr. Beaudet believed it possible to unsilence the paternal gene.

With this news, Terry Jo, impatient for any progress in the field, went back to school to get a PhD in neuroscience determined to discover a compound that could unsilence the paternal gene. As she continued to work on as many experiments and studies as she could in graduate school, the field started to get a lot of attention.

Everything for Terry Jo changed when a young scientist at the University of North Carolina, Ben, completed the experiment that she had hoped to do. He looked at thousands of compounds and found that a cancer drug that could unsilence the paternal gene.

Breakthrough moment

Dr. Beaudet suggested Terry Jo get in touch with Ionis, where work was underway to determine whether. the company’s antisense technology could help her achieve the goal of disrupting the defective, or silenced chromosome. Positive about pursuing change for the AS community, Ionis welcomed families, representatives from foundations, and reviewed notebooks full of letters from all over the world expressing a strong desire for a genetic treatment, despite the fact that the greater AS community was still debating whether or not a cure was possible.

Today, Ionis hopes to begin clinical trials in patients in the near future for a treatment thought to help those with AS, instilling new hope for a brighter future. To this day, Terry Jo believes in the power of information. Because she never stopped seeking answers for Lou, she found Ionis, which may hold the key to a new tomorrow for those with AS.

Sonia and Eric’s story

An unknown illness

In 2010, an otherwise healthy mother and poet named Kamni started to experience weakened eyesight. Kamni’s journey that started as a few visits to the ophthalmologist soon escalated into a dizzying array of specialists as both her mental and physical decline progressed. Testing Kamni for everything under the sun, from heavy-metal poisoning to Lyme disease, meant only one thing was for sure—Kamni’s illness was unknown.

Finally, in December 2010, Kamni’s family received the diagnosis that had been elusive for so long—prion disease. Prion disease occurs when normal prion proteins, found on the surface of many cells, become abnormal and clump in the brain, causing memory problems, personality changes, and trouble with movement—many of the same symptoms that plagued Kamni as the prions aggressively made their way through her brain tissue, causing irreparable damage.

Prion disease is currently incurable, this diagnosis didn’t bring relief for the family, and Kamni passed away in late 2010.

Taking action in the face of uncertainty

An autopsy revealed that Kamni’s prion disease was a genetic subtype sometimes called fatal familial insomnia (FFI), and through predictive testing, the family learned that Kamni’s daughter, Sonia, would eventually succumb to the disease that took her mother’s life. Prion diseases are extremely rare. Between all of the different subtypes, which include Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker disease (GSS) in addition to FFI, only about 300 cases are reported in the US each year.

This news sparked a new life pursuit for Sonia and her husband, Eric. Although Eric had recently completed his master’s degree in Urban Planning at MIT and Sonia had graduated from Harvard Law School, they both eventually quit their jobs to focus on finding a cure full time. For the next few years, refusing to sit back and let the disease ravage her family, the couple was determined to live and breathe the science of the disease. But as the couple got deeper in research, the gravity of their challenge began to sink in. Hope they originally felt while unearthing preliminary research crumbled as limitations of possible treatment approaches became evident, due in part to the challenge of identifying a strategy that could stop brain damage before it’s too late.

Breakthrough moment

During this time, the couple met Jeff , a scientist who partnered with Ionis to develop a therapy for Huntington's Disease, a disease with which he had been diagnosed. Similar to Jeff’s work with Ionis, Sonia and Eric learned that Ionis’ antisense technology may also help make a positive difference in the lives of those with prion disease.

The next big challenge for the couple was to recruit people at risk for genetic prion disease to the natural history study they are helping to run at Massachusetts General Hospital. With a disease so rare, recruitment may be a challenge. But with renewed hope and purpose, there’s no telling how far their pursuit will go.

Chuck’s story

A family diagnosis

In Chuck’s family, the awareness of hATTR amyloidosis started with his uncle Bill, who was on a mission to find out what was wrong with him. He called an Amyloidosis Center of Excellence, gave them his symptoms, and within a week saw a doctor who diagnosed him.

But the diagnosis did not stop there as Bill suspected others in the family should be tested as well. Bill's sister, who is Chuck's mom, was the next one who received a positive diagnosis. After his mother was diagnosed, Chuck went for testing and found out he was also positive for hATTR.

Out of 24 family members who were tested, 18 are positive—including two out of Chuck’s three sons and his two remaining siblings.

Hereditary ATTR amyloidosis (hATTR) is an inherited disease that often affects the liver, nerves, heart and kidneys. The disease is characterized by the deposit of an abnormal protein called amyloid in multiple organs of the body where it should not be, which causes disruption of organ tissue structure and function. The amyloid deposits most often occur in tissues of the nervous system, heart, and digestive tract.

Chuck’s first symptoms were autonomic issues, such as nausea, vomiting and diarrhea, and he thought it was just part of getting older. But as he became more symptomatic, hATTR started to completely change his life.

A rare disease that robs its patients

Later, he developed additional polyneuropathy symptoms, such as pain in his hands and feet, loss of grip and dexterity in his hands, balance issues, stumbling and falling and tingling and numbness in his hands and feet. These symptoms got so bad he felt like he could not carry his grandchildren. Active throughout his life, he enjoyed riding his bicycle, dancing, and racing motorcycles. But hATTR robbed him of what he loved.

Breakthrough moment

Chuck was just about to give up when someone from his support group told him to go to a meeting about an Ionis clinical trial studying an antisense drug that was designed to decrease the amount of mutant and normal TTR made by the liver. Chuck met the criteria for the trial and began participation, and was excited at the potential to help those living with hATTR.

With optimism for the future for himself and his sons, Chuck’s advice to anyone living with this disease is to face it with strength, and to be thankful that hope has been renewed for those living with hATTR.