STOW — Genetic diseases — those linked to a person's DNA — were once considered untreatable, as family members were tested and counseled with limited choices.
Now, new breakthroughs in gene therapy may offer hope for a cure.
For one Stow family, that hope can’t come soon enough. Mike Collins, 28, didn't show any signs of the genetic mutation he inherited from both parents until he was 6 years old. Neurological symptoms began slowly with blurry vision and quick arm jerks, progressing to grand mal seizures that became worse with age.
He often fell, suffering cuts, bruises, broken bones and concussions. In 2017, he was diagnosed with Unverricht-Lundborg Disease by University Hospital's Center for Human Genetics. Now Mike sits in a wheelchair waiting for a possible cure through gene therapy.
Mike’s mother, Michele Collins, is executive director and founder of Hope for ULD and is raising funds for research for those born with Unverricht-Lundborg Disease.
"In the last years, a major discovery was made of a harmless virus called AAV that dwells in humans," said Dr. Berge Minassian, director of gene therapy at the University of Texas Southwestern Medical Center. "It was then shown that the gene in a brain genetic disorder can be packaged in this virus, and the virus will function as a delivery truck to deliver the gene to the cells of the brain, making the cells complete again."
Many diseases, especially brain diseases, are caused by single gene defects, Minassian said. In other words, of the thousands of genes that contribute to brain’s functions, one is missing.
"At this time, the AAV viral technology is such that gene therapy can treat single-gene defect diseases," Minassian said. "However, the experience garnered in these diseases is setting the stage for someday treating the more complex common diseases with gene defects in multiple genes."
Like ULD, Huntington's disease is another with a single gene defect. Multiple gene defects at the same time can cause Alzheimer’s disease or autism.
"Single gene defect diseases are much rarer than polygenic diseases," Minassian said. "However, since the brain needs about 20,000 genes to function normally, diseases with single gene defects collectively outnumber any common disease."
Michele taught school in Twinsburg for 15 years — but as Mike's symptoms worsened, she quit her job with the district to care for him. By the age of 19, Mike had relentless epileptic seizures, jerks and twitches. Bright lights, crowds, noises and even thinking caused seizures.
"Medication kept them under control at first," Michele said. "He was starting to have so many difficult emotional and physical side effects, doctors added a fourth medication to control the side effects."
Those side effects included constant tremors, brain fog, severe stomach and head pain, suicidal thoughts, severe depression and fatigue.
Throughout school Mike was able to participate in sports and worked in a grocery store, but he lost coordination over time, Michele said.
The illness has taken a toll on Mike, said his father, Kerry. Mike was one of the best baseball and basketball players, but his skills declined rapidly. He would stand at the plate and couldn't get out of the way of the pitch because the medicine made his reactions so slow.
"He'd have a giant muscle jerk and land on his face," Michele said. "He's 6 foot 2 and went down like a tree and had no way to stop himself. He's had a lot of injuries and a lot of concussions."
Previous genetic testing showed nothing, and the family had no real answers early on, Michele said. They did not know ULD was a progressive disease, and Mike was suffering more and more.
"My husband and I wondered how much he could endure," Michele said.
Mike started having difficulty talking and swallowing, she said.
"He’s gotten depressed because he can't play sports, work and have a girlfriend like others," Kerry said. "It's a psychological battle. When he has seizures, he is upset. I don't know if he believes in being cured."
Michele said that once the family had the diagnosis, with the knowledge that both she and Kerry were carriers of the gene, it was a tremendous relief.
"Before, it was a shot in the dark to try to relieve his suffering," she said.
Michele spent many hours contacting researchers all over the world, desperate to find a way to alleviate Mike's suffering — which led her to Dr. Minassian.
"He, along with molecular biologist Dr. Steven Gray, is developing gene therapy for devastating single gene epilepsies," Michele said. "They are working on various diseases, in various stages of research, several (are) about ready to go to human clinical trials this year."
It is the Collins’ hope that Mike can be part of those trials.
Minassian said he was interested in ULD because he had spent his life studying its sister disease, Lafora — and both are devastating progressive epilepsies.
"Our bodies are the products of our genes," Minassian said. "With the exception of diseases caused by harms to our body, most diseases one way or another are influenced, or exclusively caused, by problems in our genes. This goes beyond brain diseases and includes all organs and all cancers.
"As such, genes are root causes of many if not most diseases, and thus gene therapies are crucially important to the medicine of the future, including the immediate future."
About a year ago, Michele said she located other families who were interested in pursuing gene therapy for their loved ones, and founded Hope for ULD.
So far, the group has raised $27,000 and would like to reach $100,000 to begin research, which costs $300,000 for the initial phase, Michele said.
If the trials are successful, researchers can obtain money from biotech companies and government grants — and Hope for ULD can continue to raise funds for gene therapy research and treatment, Michele said.
The hard part is getting initial funds to get the research off the ground.
"Gene therapy addresses the problem at the root cause, and when the technology reaches maturity it will be a permanent fix, because the very code of the problem would be corrected and not the downstream product," Minassian said.
Kerry says the diseases being treated with gene therapy give him hope for a cure.
"All the doctors could do was treat the symptoms with medicines that had bad effects," Kerry said. "Now they can get to the root cause and cure it."
Gene therapy is a new frontier and could mean incredible breakthroughs, Michele adds.
"I feel very privileged to be part of this," Michele said. "For 20 years, my husband and I wondered how much pain can Mike suffer. Now we know the cause and have a doctor who can help."
In spite of his condition, Mike has retained his sharp wit, sense of humor and heart of gold.
"He once told me that the worst thing about his condition was not being able to help other people," Michele said. "He wishes that he had the opportunity to live life like any other 28-year-old man. He has been on disability, unable to work for years and is very excited about the possibility of working again."
Michele says Hope for ULD is working on an upcoming fundraising dinner. For more information or to give, go to https://www.hopeforuld.org/ or email@example.com.
Reporter Laura Freeman can be reached at 330-541-9434 or firstname.lastname@example.org