Greg Bennett lives with a medical condition named Metachromatic Leukodystrophy, or MLD.
Greg Bennett's challenge is remaining free of the prison of other peoples' perceptions. It is keeping loose from restrictions on his movement and his personal growth. It is exceeding the expectations that would set an expiration date on his dreams. Greg's Challenge is also a website, www.gregschallenge.org, that tells the story of a 19-year-old man who, with the support of his family, is fighting the odds.
"I am living with a rare neurological disease that's called MLD for short — metachromatic leukodystrophy, if you want the scientific version of it — and it's a struggle," Bennett will tell you.
MLD is a neurodegenerative disease that leads to progressive muscle failure and loss of mental faculties. People Bennett's age with MLD lose their coordination and eventually lose the ability to walk. They develop dementia and they go blind. There is no cure, and existing treatments are extremely risky.
And yet Bennett has managed to beat his doctors' predictions that he would be confined to a wheelchair by now, two years after he was diagnosed with MLD.
Far from being off his feet, Bennett works out on an elliptical machine and lifts weights twice a week, attends church youth group meetings, and volunteers once a week at a senior center. He has lost some strength and coordination and he tires easily at times, but he is determined to make the best of what he has.
"I have this disease, and I am living it day by day," Bennett said. "I am living my life day to day, and I live it like it's my last."
In fact, when meeting Bennett for the first time it's a challenge to notice anything is different about this handsome young man with the bright smile.
There are a few tells, but only if you look closely: As he sits at the kitchen table of his family's home in Westminster, he is engaged and making eye contact and gesticulating while speaking, but he doesn't always know what to do with his hands when not involved in an activity. He blinks frequently and his gaze wanders, as will his speech at times, while at others he falls silent for long moments in order to gather his thoughts before finishing a sentence.
Sometimes the words come quickly but they come out wrong, as when he called out, "good night," after his younger sister Emily Bennett sneezed.
As subtle as those symptoms might seem at first glance, they belie frustrations of a young adult trying to make friends and live his life, all while dealing with an illness most people don't know exists, according to Wayne Bennett, Bennett's father.
"That tends to be, at least in those who have the adult form of MLD, the most difficult — the social awkwardness, the social ineptness," he said. "People looking at him physically and saying, 'Hey, he's normal,' and then suddenly talking with him or maybe seeing him act out certain things and coming to the conclusion that something is not right here."
Greg Bennett is always asking himself after he meets someone for the first time if he left a good impression.
He's begun telling people soon after he meets them about his disease. He hopes it will help people to understand him, to not judge him and to take a chance to form a connection with him. He hopes it will help raise awareness of MLD.
Monday, Feb. 29, is Rare Disease Day, and MLD is one of the rare ones, with just 1 in 40,000 people suffering from it. For Greg Bennett and his family, the hope is that by telling his story, more people can become aware of MLD, raise funds for research for MLD, or seek early diagnosis or treatment if it affects someone they love, according to Greg's mother, Pam Bennett. She knows it is important for other families to know they are not alone.
"We are living our new normal," Pam Bennett said. "Our focus is to raise awareness, and hope and pray that somebody somewhere is going to figure this out and find a cure."
The elementary school years went exceptionally well for Greg Bennett, in a time when he did well both academically and socially, according to his mother.
"He was the straight-A, rocket-scientist kid," Pam Bennett said. "He had a lot of friends, had a lot of fun, was very athletic, was well liked by kids and teachers and everybody."
Middle school brought some changes and concerns. Greg Bennett's grades started slipping and he was getting in trouble in class, but his parents, his pediatrician and a counselor all believed these were just behavioral problems, part of growing up.
"I have this disease, and I am living it day by day. I am living my life day to day, and I live it like it's my last."
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"It wasn't until he got into ninth grade that we were recognizing that his school work was seriously declining and that his reading comprehension wasn't what it used to be," Pam Bennett said. "We brought it up again with the pediatrician, and they kept saying it's behavior, it's psychiatric, there is nothing going on."
Greg Bennett moved from one counselor to another, and from Westminster High School to Gerstell Academy to North Carroll High School, for his senior year, where for a time things seemed to improve. All the while, Bennett said, he thought everything he was experiencing was normal and commonplace — even the times he would be helping a friend and then realize that friend wasn't really there.
"It kind of all came to a head in January  of his senior year. He went to the crisis counselor, and he was hearing things and seeing things, and [the voices] were telling him to hurt himself and to hurt other people," Pam Bennett said. "We went to another counselor and she told us, 'You need to go to the emergency room.' "
Greg Bennett was admitted to the psychiatric unit at Carroll Hospital that month with a diagnosis of first break schizophrenia, which Pam Bennett, who is a nurse, said is common in males his age. But during the week Greg Bennett was in the hospital, she just couldn't quite shake the feeling that something else was going on. She began requesting an MRI.
"They ordered it, they canceled it; they kept saying, 'It's definitely schizophrenia. He doesn't need it.' I told them I wasn't leaving, I wasn't taking him out of there until they had it done," Pam Bennett said.
The MRI came back abnormal, and the neurologist told them that Greg Bennett had a form of leukodystrophy and that they should call Johns Hopkins Hospital. It was the first time his mother had heard the term.
"I've been a nurse a long time. I've done hospice, I've done home care. I've been around the block, so to speak, and I've never heard of it," Pam Bennett said. "I remember Wayne asking, 'Is it like [multiple sclerosis]? Is it something like that?' "
No one, Pam Bennett said — not herself, not Wayne, not Greg, not even the neurologist — seemed to have any inkling of how serious this diagnosis was initially, but a quick Internet search changed everything.
"It's terminal, it's rare, there is no cure, etc. Forty different types," Pam Bennett said. "I was just flabbergasted."
She left a message for a different neurologist who had treated Emily Bennett for a concussion, hoping to learn something that contradicted all of the negative things they had found in the hours they had been scouring the Web in a crash course on leukodystrophies.
"The next day, she called me and I told her that they were telling me Greg has leukodystrophy, and the first thing she said was, 'Oh, no,' " Pam Bennett said. "I thought, 'Oh God, that means everything we read was true.' "
In the brain there is gray matter, composed of brain cells called neurons, and white matter, the long axons of the neurons that stretch like wires from one part of the brain to another and down the spine like a bundle of wires. These are nerves.
White matter is white because each nerve is electrically insulated by a sheath of fatty substance called myelin. This insulation is what allows nerve signals to propagate all the way from the motor cortex in the brain to, say, your left big toe.
Leukodystrophies are genetic disorders that result in the degeneration of the white matter in the brain and spinal cord, with "leuko" referring to the white matter and "dystrophy" to the degeneration. As nerves lose this myelin coating, communication breaks down and the characteristic symptoms — loss of coordination and movement, cognitive impairment — begin to appear.
A person with metachromatic leukodystrophy — "metachromatic" refers to changes in the color of nerve tissue as a result of the disease — does not produce, or does not produce enough, of an enzyme called arylsulfatase-A, according to Dr. Ali Fatemi, director of the Moser Center for Leukodystrophies at the Kennedy Krieger Institute and a pediatric neurologist who monitors Greg Bennett. This enzyme normally breaks down fats called sulfatides, but when it is absent, the sulfatides can build up in the cells that make up the myelin sheath around nerves, leading to the degeneration of white matter.
"It's a so-called autosomal recessive disease, which means that you have to have two bad copies of the gene that is affected," Fatemi said. "You typically inherit one copy from the mother and one copy from the dad, and so therefore parents who have only one bad copy — because we have every gene twice — they have no symptoms."
About 1 in 100 people are an asymptomatic carrier of the gene mutation that leads to MLD, according to Fatemi, and the odds that Wayne and Pam Bennett — who could not have known they were carriers — would come together to make a family was 1 in 10,000, but for each of their children, there was a 1 in 4 chance they would be affected.
Greg Bennett inherited MLD, while his sister is a carrier like her parents.
"Unfortunately, we hit both of the affected odds," Pam Bennett said. "In Emily's favor, she can have testing of her future spouse, and if he happens to have this genetic mutation, then they can plan accordingly."
Things could have been very different for Greg Bennett. MLD actually presents in three different ways, according to Fatemi, the most common of which is the infantile form.
"It starts in late infancy. These kids initially appear normal for perhaps the first year or six months of life and then start really crashing really fast and basically die within a couple of years after symptom onset," he said. "It's a really dramatic presentation."
The childhood or juvenile form of MLD starts in the school years and is not as rapid a progression as the infantile form but can be rapidly devastating in some patients, according to Fatemi. Greg Bennett has developed a later form of this presentation of MLD.
But there are also adults who develop MLD in midlife or later, taking decades to run its course, and Fatemi believes there might be many more of these patients out there than is currently recognized.
"They typically have a similar history to that Greg had; they get misdiagnosed as a psychiatric disorder," Fatemi said. "These are often psychiatric patients that die and then at autopsy, they find that they had MLD."
Rare disease and misdiagnosis
It's a difficult thing for Pam and Wayne Bennett to think back on all the years they struggled to help their son, never knowing they were operating on an entirely incorrect premise.
"We are always thinking: He's not trying. He just doesn't give a damn. It got to the point you would be yelling because you are so frustrated, 'What is wrong with you?'" Wayne Bennett said. "If we had known, we could have bypassed that."
One of the reasons Greg Bennett and his parents want to get the word out about MLD is because they don't want anyone else to suffer through that period of not knowing.
Shortly after Bennett was diagnosed, Pam Bennett joined an email list, through the MLD Foundation, of about 300 families dealing with MLD. Through the list, she heard stories of other teenagers with MLD and their trials and tribulations before arriving at a diagnosis.
"Things happen and they lose jobs. They don't stay on task and they kind of have risky behaviors — there have been a couple of them that have gotten pregnant or have gotten other people pregnant," she said. "They have kind of been perceived as the black sheep of the family until it's suddenly realized, 'Oh no, they actually have this disease.' "
If nothing else, Pam Bennett hopes spreading the word about her son's story and MLD will lead to more medical professionals learning to recognize it.
"My thing is tell your doctor. I am surrounded by medical people every single day; I have only met two people outside the leukodystrophy world that have ever heard of MLD," she said. "I want people to know it like they know ALS [amyotrophic lateral sclerosis, also known as Lou Gehrig's disease]."
The other thing about early diagnosis is that while there is no cure for MLD, there is a treatment that can successfully slow the progression of the disease, but it's best used as early as possible once the disease develops and is not without some risks.
"The only standard approach right now is what we call allogeneic bone marrow transplantation — allogeneic meaning it is the bone marrow from somebody else," Fatemi said. "Those bone marrow cells from the healthy donor, they have no gene mutation, so they have an intact enzyme."
The concept is that after the transplant, the immune cells from a donor's bone marrow that express the enzyme arylsulfatase-A will migrate to a patient's brain to replace the immune cells there, according to Fatemi. But there's a catch: First you must wipe out the MLD patient's native immune system with heavy chemotherapy.
It's simply too risky for her son, according to Pam Bennett. Any time Greg Bennett is sick or stressed, she sees the disease progress a little, and a bone marrow transplant would be a huge tax on his system.
"It's a huge gamble. You hope to come back up and plateau and remain stable," Pam Bennett said. "But with my hospice experience, I don't want to preserve his wheelchair years. I want to preserve what he can do now."
It was in early February two years ago when Pam and Greg Bennett were at Hopkins undergoing the testing that would reveal his diagnosis, and Bennett recalls one moment that will always stick out in her mind. A geneticist was working with Greg, and she asked him how it felt to know his life would be cut short.
"He looked at her and said, 'How do you know? I'm an anomaly,' " Pam Bennett said. "I was like, wow, is he saying that for my benefit, or does he really believe that?"
Two years after that dark day, Pam Bennett has come to realize that the answer is that it was both: Greg Bennett was being brave for her benefit, but he also really believed he was an anomaly. He was right.
"We are at two years, and he is not in a wheelchair and he is not significantly worse," Pam Bennett said.
There still is no cure, but they have found some strategies that help.
'It's a dirty disease'
In the summer of 2014, the ALS Ice Bucket Challenge swept social media in a viral storm of fundraising for research into that disease.
According to Pam Bennett, "Greg got a little bit angry at one point and said: 'They are making all this money for ALS, what about my disease? Why can't we do something to raise awareness for my disease?' "
Together, they put the question to the email list of MLD families: Could they design a viral campaign to raise awareness and funds for MLD?
"They wanted to do 'Let's get muddy for MLD — it's a dirty disease,' " Greg Bennett said. "It's dirty because it shoots low and takes away a lot of the normalcy of people's lives."
It was an excellent theme, but neither Pam or Greg Bennett really wanted to pour mud on their heads, so they set aside the idea until Pam Bennett showed up at work one day to see all of her colleagues wearing bracelets made of brown wooden beads, and letter "G" pendants.
"When she asked them, someone came up to her and told her they were all praying for me," Greg Bennett said.
It was exactly what they had been looking for.
"These are perfect. These are brown, the dirt is brown; we can get dirty without getting dirty," Pam Bennett said, describing the epiphany she had. "What if I can get Greg to make these bracelets and somehow use it as occupational therapy so we can get rid of his hand tremors?"
Today, Greg Bennett has made more than 300 bracelets and offers them on his website in exchange for donations for the MLD Foundation. His hand tremors have diminished enough to surprise Fatemi. He bought a bracelet, too.
"I told him I think the repetition of stringing the beads has caused a new pathway in his brain, and [Fatemi] said, 'I think you're right,' " Pam Bennett said. "He said, 'Whatever you're doing, you need to keep doing it.' "
Hope around the corner
As grim a diagnosis as MLD can be, and despite the paucity of medical tools available to combat the disease today, there is a wide range of promising clinical trials planned or underway that could totally change the landscape of its treatment over the next five years, according to Fatemi.
"We are in a very hopeful time," he said. "Really, for the last few years, the biotech industry has been focusing more on rare diseases than they used to."
Both Wayne and Pam Bennett believe that infant testing for MLD could be a game changer, allowing patients to begin treatment long before they become symptomatic, and this is a major priority of the MLD Foundation as well, according to Dean Suhr, the foundation's president.
"We have been working very closely for several years with a researcher at the University of Washington, Dr. Michael Gelb, to develop a screen for MLD," Suhr wrote in an email. "The traditional approach of testing blood enzyme levels would not work for MLD. Dr. Gelb, with our help providing MLD blood and feedback, developed an alternative approach that uses the same equipment that most newborn screening labs have."
A preclinical trial involving blood tests of 40,000 infants is scheduled to begin sometime in the next month or so, according to Suhr.
"We are living our new normal. Our focus is to raise awareness, and hope and pray that somebody somewhere is going to figure this out and find a cure."
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There are also ongoing clinical trials for a gene therapy approach to treating MLD, according to Fatemi, a process that involves taking a bone marrow sample from the MLD-affected patient themselves.
"You take the affected patient's bone marrow, take the bone marrow cells, put them in a dish, and with a virus bring in the correct gene into the cells," he said. "You basically fix the gene defect within the cells, and then give the patient back his own bone marrow."
In France, Fatemi said, trials are underway that would introduce a virus carrying a corrected copy of the gene that is mutated in MLD directly into the brain.
"These are viruses that are very much targeting brain cells, they like infecting neurons, and they have the ability to infect cells that are not replicating," he said. "This is good in that we have a very high efficacy of what we call transfection, so being able to bring the gene into the genome of the cells."
Another approach is to find a way to simply give arylsulfatase-A directly to patients with MLD, but this is complicated by the fact that this enzyme is a large molecule that cannot easily cross the blood-brain barrier, the biological border crossing that insulates the central nervous system from the rest of the body. There are trials underway outside the U.S., Fatemi said, in which an external pump worn on the abdomen would inject arylsulfatase-A through a tube and directly into the cerebrospinal fluid in the spine, bypassing the blood-brain barrier.
In Fatemi's own center at Kennedy Krieger, meanwhile, he is currently working with a chemist on nanotechnology methods that could delivery large molecules such as arylsulfatase-A directly to the central nervous system, shepherding them across the blood-brain barrier.
"This is really taking shape, there is now some industry support for it and we are moving forward toward [Food and Drug Administration] discussions and maybe testing it in animal models," he said. "The chemist who is the inventor of this approach, who is our close collaborator here, he thinks that the enzyme is not too big and it should be doable."
All of these trials are for the infantile form of the disease, for which their success can be determined more quickly because of the rapid progression of the disease in that age group, and Bennett is not eligible to participate, according to Fatemi. As frustrating as that might be, he said the trials do represent very real possibilities for developing effective treatments that could be available to Bennett sooner rather than later.
"It is likely that something is going to get approved in the next few years. Maybe not in the FDA, but within the European system," Fatemi said. "Once you get approval for one of these interventions for the infantile form, it will be used off label for all the other forms. … I think for him there is hope."
Spreading the word, day by day
Bennett loves plants — succulents especially and anything that's carnivorous. He tends to a wide array of them in pots inside during the winter, and in the warmer months, his parents say, he will make the yard bloom.
"Plants, for me, they give me the strength that I need. I feel like I am accountable for the plants, so keeping them alive is like my …" Bennett trails off and looks down. Something has frozen up, the words jammed or the thread lost, and it's not clear if he will be able to continue — he's silent and still for just longer than feels comfortable.
And then he looks up and states with assurance and authority, "I feel like it's my responsibility to keep them alive."
It's about more than just keeping plants alive, however — it's about Bennett, and his family, really living.
In November, Bennett won a wish from the Make-A-Wish Foundation, which sent the family on a cruise of the Caribbean.
"My wish was to go see the Mayan ruins, and so I got a cruise and I went down to the Mayan ruins and went all through," Bennett said. "I went to the Mayan ruins in Mexico, I went to the Mayan ruins that are in Roatan [and] Belize, and I went to the Mayan ruins in Cozumel."
The ruins impressed, but Bennett's favorite time of day was meal time. That's when he could tell stories from each day with his family and speak with some of the friends they had made on the cruise.
"Inevitably, the best times that Greg has is when he is surrounded by people," Wayne Bennett said. "When they are truly engaged in talking with him."
Making a connection, sharing Greg Bennett's story — that's a large part of the Bennett family's life now, and Wayne Bennett said they are continually amazed at how much it affects people.
Wayne Bennett met a woman on a business flight and got to talking.
She revealed that she was a landscaper at SeaWorld in San Diego, and Bennett told her about his son's story and Greg Bennett's passion for plants. She told him to make sure he contacted her if they ever traveled to San Diego. So when the family took a trip to Southern California, they emailed her to let them know they were coming.
"We get to the hotel and at the front desk within a day or so of our arrival was a package. In the package was four tickets to SeaWorld, four tickets to the animal safari park, but what was more amazing was a cardboard box full of at least 30 different cacti and other plants that she gave to Greg to take back with us and plant them," Wayne Bennett said. "We've stayed in touch with her ever since."
Greg Bennett received a wonderful gift of plants, but more importantly, his father said, another person is now aware of MLD. Perhaps she will tell her doctor, or a friend. Perhaps someone Bennett meets at his twice-a-week physical therapy appointments will be inspired to become a medical researcher.
They might never know the outcome of sharing Greg Bennett's story, but they know they have to do just that.
"It's how you approach it, how to put a positive spin on it," Wayne Bennett said. "Your job is to find out what that is and how you can educate others, and how you can take that and make it into a positive for other people."
Greg Bennett, after all, has found a way to make things positive for himself, and when he smiles while sharing how he faces his struggles, he is sharing something valuable.
"My philosophy for living is, you live one day at a time and you should never give up," he said.