A month, half a year, a few years of life – this is what I am asking the parents of patients with rhizomelic point chondrodysplasia. Perhaps in the near future, experimental therapy will make these dreams come true.
Once a year, Crystal and Jonathan Bedford take their three kids on a 1000-mile journey from their native Texas to rural Alabama. They are huddling along the wooded shores of a lake with other parents whose children suffer from the same rare genetic condition as their daughter, five-year-old Marley.
Rhizomelic point chondrodysplasia (RCDP) is a painful form of dwarfism usually accompanied by severe mental retardation and respiratory problems. There is no cure for the disease, and children with RCDP rarely live into their teens. Families come to Alabama to learn how to care for the delicate health of their children, and in hopes of any hopeful information from the world of science. For the most part, they can only count on warmth and understanding. However, this year they received something more.
The president of a Canadian biotechnology company came to the meeting with the parents, inviting sick children to participate in next year’s clinical trials. At first, the news seemed too good to be true by my parents. – You don’t want to get your hopes up, what if something goes wrong? What if this research is not done at all? What if they don’t help? Says Hannah Peters, mum of 16-month-old Jude, a boy with RCDP. “On the other hand, never before, since Jude was born, has no one given us hope.
This is the fate of parents of children with rare diseases. They do their best to understand their child’s ailment and provide them with the best possible care, they look for the best doctors, which often involves enormous costs. And although the pharmaceutical industry is increasingly involved in research for a small population of patients, some of them will never receive help.
Meanwhile, RCDP is one of the rarest diseases on earth. Experts estimate that there are no more than a hundred sick people in the world. Support for children with point chondrodysplasia came from an extraordinary coincidence: a scientist from Montreal, Nancy Braverman, who spent decades of researching RCDP, encouraged the president of a biotechnology company to cooperate. The company, Phenomenome Discoveries, has already developed agents that can replenish sick children with what they need most: plasmalogens, a type of phospholipid found in cell membranes. Phenomenome Discoveries took an interest in plasmalogens because some studies showed that people with Alzheimer’s disease also lack them.
Nobody is presenting synthetic plasmalogen precursors, developed by a Canadian company, as an effective drug for RCDP. Yet, if plasmalogen levels in the blood and lungs of children with the disease could be increased – as was done in laboratory mice – Braverman believes that the respiratory function of young patients could be improved, possibly extending their lives. “For parents like us, every additional month with a child, or a year or five, is all we’d like to ask for,” remarks Crystal Bedford.
Many issues remain unanswered, but the parents getting ready to meet Dayan Goodenowe, president of Phenomenome Discoveries, intend to throw questions at the visitor anyway. Well, what if it is not possible to collect a sufficiently large group of respondents, taking into account the rare occurrence of RCDP? What if the company doesn’t raise enough money to complete the research? And, the bottom line: what if the experimental treatment fails to improve at all? – Is this really happening? Wonders Bedford, who runs a frozen yogurt shop with her husband. – What are our chances in real terms?
To his parents in Alabama, Braverman is halfway between a rock star and his beloved aunt. Nearly 20 years ago, a scientist identified the gene causing RCDP and devoted her entire career to this disease and related issues. As a doctor, she regularly leaves her lab to meet patients and parent support groups.
About five years ago, Goodenowe approached Braverman after learning that the researcher had managed to obtain mice deficient in plasmalogen in the laboratory. They began working together, and when plasmalogen precursors raised levels of these cells in the blood and lungs of mice, they began considering clinical trial plans for people with RCDP. Before meeting Braverman Goodenowe, he didn’t even know that such a thing as RCDP even existed.
The drug, which is a combination of three synthetic plasmalogen precursors, has entered the last stage of preclinical research. Goodenowe’s company will apply for approval for clinical trials in children with RCDP early next year. (…) One of the plasmalogen precursors is also going to be tested on a group of Alzheimer’s patients.
If US authorities approve the 18-month Phenomenome Discoveries study, participants would receive liquid precursors two or three times a day, starting next summer. Every six months, the children would go for tests to Alfred I. duPont Hospital for Children in Wilmington, Delaware, where the child geneticist Michael Bober would assess not only possible improvements in their respiratory system but also look for beneficial changes in motor skills, height and height. , neurological functions and many more.
Bober – “smutas,” as Bedford jokingly calls him – tries to cool his parents’ enthusiasm. Calling the results of tests on mice “promising” is considered by the geneticist to be abusive. – We should not get too excited about the potential of something that has not yet been tested in practice – he says. And whether the drug will really work is difficult to check in a population of 10-20 people, adds the doctor. – It would be different if we could give it to 20 patients to check its effectiveness.
Families with children suffering from RCDP seek each other through RhizoKids International, a support group founded by two mothers in 2007. Both of these women, Tracey Thomas and Mary Ellis, continue to lead the group, even though their children have died. They raise funds for research and search the internet for the latest RCDP news. This is how they found the articles by Braverman, an assistant professor at McGill University. They wrote an email and the researcher volunteered to come to Alabama to examine their children. Thus, in 2008, annual reunions were initiated at a modest tourist resort by the lake, near the Ellis house. Braverman participates in them regularly. – As a rule, scientists do not provide such opportunities for contact. They’re examining the cells but not holding the baby, Thomas notes.
16 families came to this year’s reunion, even from places as far away as Brisbane in Australia. Some of the children are as small and light as babies, though they have long reached preschool age. The oldest brother and sister are from Ohio, ages 9 and 13, and their longevity is enjoyed by the RhizoKids community. The case of Marley Bedford is also special, as she has an exceptionally high level of plasmalogen among children with RCDP. The girl walks, plays and talks, although she has deformed bones, painful muscles and joints, and deteriorating eyesight. By comparison, most RCDP patients will never learn to sit, walk, talk, or eat by themselves. Milestones in the development of these children are often the ability to smile and laugh, although young patients also learn to respond to familiar voices and to music – for one child it will be recorded bird singing, for another – Adele’s album. “We’d be over the top if we could make the average RCDP kid into someone like Marley,” says Bober.
Hannah Peters has been in contact by phone and Facebook with other parents of sick children practically continuously since her son, Jude, was born. She was afraid of her first trip to Alabama. “All parents talk about it: what frightened them most was the prospect of seeing their older children with RCDP,” comments 23-year-old Peters, who attended the convention with her husband Sullivan, parents and other family members to support. – It means a hard hitting reality because you can see what these kids cannot do. On the other hand, you gain hope because they are still alive.
Jude has become a celebrity of sorts thanks to his parents’ wise use of social media, through which they collect donations for the treatment of their son and a campaign to raise public awareness of his disease. The boy’s Facebook page has 32. fans, and Jude receives so many letters that his mother rented a separate mailbox for him. But Jude is the opposite of Marley: she has extremely low plasmalogen levels and has severe respiratory and digestive problems. Since his birth in April 2014, he has been hospitalized five times. His mother cried out when Crystal Bedford called to tell her about a possible treatment option.
Jude and other children with RCDP require intensive treatment for their stiff muscles and joints. They ride in special carts padded with foam and towels to reduce their discomfort. They have to be kept in a special way, and only during the annual meetings in Alabama, parents can pass their children on to each other without fear that they will risk fractures or additional pain. “Opportunities like this light up our monotony and create opportunities for contacts with others,” says Melinda Holladay from California, mum of 8-year-old Ethan.
During a three-day meeting, Bober and Braverman examine each child by placing them on a table, where they measure by entering the data into a register funded by the RhizoKids Foundation. The register is intended to provide parents and doctors with information on how quickly a child with RCDP should gain weight to avoid overfeeding. The doctors examining Jude wondered about the two brief fits the child had experienced earlier that day. Bober asked the boy’s parents about his hopes for clinical trials: what changes would they expect in Jude’s functioning? Peters doesn’t know where to start. A stronger respiratory and immune system responds. The ability to “speak to us, reach out to us, give us a hug.” (…)
For Crystal Bedford, the most important thing would be to improve Marley’s respiratory system and improve her vision, because she was starting to lose her eyesight. – And if you could make a more polite child out of her, it would be fantastic – he jokes, referring to the stubbornness of the little girl. Everyone around bursts out laughing, the tension is released from them.
Goodenowe admits that he could use 30 study participants. Healthcare has data on 24 children with RCDP, but “some of them have passed away,” the head of Phenomenome Discoveries says in a tactful manner. But a smaller group can also pass the test, provided that there is a way to objectively measure the effectiveness of the drug. – Raising the level of plasmalogen must translate into a change in functioning – this is our goal – he emphasizes. – If we fail to improve functioning, no one will listen to us.
On the evening before the families returned to their homes, balloons with LED lights inside flew into the sky: they floated like ghosts over the lake, reminding them of the dead and providing entertainment for those who are still struggling with the difficult reality.
The difficult reality was to catch Jude’s parents soon: the boy was hospitalized for a week due to intestinal obstruction. Specialist studies have shown epileptic discharges in the brain and the baby is now taking two anti-epileptic drugs.
Hannah Peters says the prospect of her son’s participation in clinical trials encourages her, although she is also very upset about it. – I met these people, we spent time together and gained confidence in them – says my mother. – They really care about saving our children.