Tuesday, December 15, 2015

Metachromatic leukodystrophy

If there ever comes a time in your life that you are feeling sorry for yourself, take time to stop and think about the short but triumphant life of Audrey Ann Fish Haberman.

Audrey lived only two and a half years, but in that brief -- but awe-inspiring -- time, Audrey endured more than most who have lived much, much longer.

The first-born child of Erica Fish and Sam Haberman suffered greatly during her 935 days of life, but there were good moments, too.

Moments so memorable, sweet and agonizingly heart-breaking that Audrey's parents. grandparents, caregivers and companions will remember her ordeal as long as their earthly journey continues.
Audrey truly was one in a million . . . if not one in multiple millions.

She had a rare disease with a name so long it scares you to even say it. As spelled out by Erica and Sam at "An Evening for Hospice," the terrible, incurable disease is called metachromatic leukodystrophy.

When we remember Audrey, we probably should say the complete name of her illness to remind us of her struggle, but being human we abbreviate, saying simply "MLD" instead.

Listening to Erica and Sam at the Hospice evening at the Knights of Columbus Hall in McCook, it was awesome to consider all the places Audrey visited during her alternately painful and pleasurable life.

In her 133 weeks of life, Audrey spent time with her parents and grandparents in Omaha, Oklahoma City, Philadelphia, Europe, Dallas, Denver and Imperial. Some of her happiest moments were spent with her young uncle Isaiah and her neighbor's dog Stella, which Audrey lovingly called, "Lella, Lella."

During most of Audrey's life, her parents knew she was very, very sick, but there were other moments, too, moments of better health and hope.

Nights being crabby -- when she cried, cried and cried -- were followed by happy times, playing with dogs and delighting her Mom and Dad with her precious antics. And, then, as Audrey's condition worsened, came the falls, dislocations and -- finally -- arms which were locked in place and hands which dangled at her side.

Near the end, Mom and Dad received the diagnosis which they feared, but expected. Audrey's disease -- MLD -- was incurable and terminal. Knowing there wasn't much time left, Sam and Erica brought Audrey back to Imperial. Upon the advice of specialists in the U.S. and abroad, who knew there was no cure, Erica and Sam reached out for Hospice care.

With tears in her eyes, Erica remembers that moment when she connected with Jim Ulrich and the Hospice team at Community Hospital in McCook,

Despite the distance and not knowing anything about MLD, the Hospice team in McCook agreed to give all the care and support it could to Audrey and her family during the final days of her life.

She survived eight weeks after the diagnosis. The last days were agonizing, her pain so great that at the very end Audrey's death was a blessing, uplifting her from earthly pain to heavenly bliss.

In celebration of Audrey's life, the cover for the 2015 Hospice program quotes the lyrics of Alabama's song, "Oh, I believe there are Ã…ngels among us, sent down to us from somewhere up above. They come to you and me in our darkest hours. To show us how to live. To teach us how to give.To guide us with a light of love."

With Sam and Erica, we join in believing that "little Audrey has a special place in heaven."



  1. The schools’ choice award winner — selected by judges from Dartmouth High, Halifax West and Prince Andrew High schools — was the United States entry The Competitor. The Lion of Courage Award, for a person who shows great courage in the face of daily obstacles, went to Bedford’s Laura Osborne, featured in the film Laura’s Dream, about her battle with the rare disease metachromatic leukodystrophy and her community’s efforts to raise funds to help find a cure.


    Words can't explain how proud we are that Laura's Dream has won "Best Documentary" at the 2015 ViewFinders Film Festival. Thanks to Meagan Brown, film-maker and fellow dreamer, we know that Laura's journey as a teacher has extended far beyond what we could have hoped and dreamed for. Please, if you haven't yet, take 5 minutes to watch Laura's **award winning** documentary, and share her message.

    Laura's Dream
    Laura has wanted to be a teacher since she was little, and her Metachromatic Leukodystrophy diagnosis hasn't stopped her. Hear the stories of what she teaches...



  2. Thaine Turner is in constant pain as he suffers from a rare incurable illness which has baffled doctors and left him unable to sit, stand, crawl or talk, but his mother Heidi Myers is appealing for people to help him enjoy life to the max.

    Heidi said: “The condition is so rare even the doctors don’t really know what it is or how to treat it.

    “There is no cure for it. It has ripped our family apart.

    “It has been really difficult for his brothers, and difficult to come to terms with the fact their brother is not always going to be around.”

    Thaine has metachromatic leukodystrophy, a genetic disease affecting one in up to 166,650 births, the equivalent of nearly six children in every million.

    It causes his nerves to lose their protective covering, meaning he is in constant pain and suffers from muscle spasms.

    He has lost the ability to move around and will eventually lose his sight and hearing.

    Most children with his form of the disease do not live past the age of five.

    Thaine spent his early months playing like any other child, until March this year when he suddenly went downhill.

    Heidi was told of his diagnosis in July this year and she is now raising money for research for the disease and to give Thaine the chance to experience the world before he goes blind.

    Heidi wants to give Thaine the chance to visit parts of the UK with his brothers, Addison, aged 16, and Braedon, aged 18, who goes to Weston College.

    Heidi, who lives in Highbridge, said: “I want my son to go out and experience everything he can while he can.

    “But I also want to raise money for research for the condition.

    “There is not a lot out there for people who have got these rare conditions.

    “We know at the moment there is nothing out there to help my son, but I would like to think there is going to be something one day to help other people.

    “If it helps someone 10 years down the line, that is great and it is a legacy for Thaine.

    “Even if we don’t raise a lot of money, I can at least raise awareness.”

    Heidi said she had always known there was something wrong.

    But she said: “We had to push and push doctors and keep going back.

    “He kept losing the skills like walking unaided and started to do less and less.

    “I want to tell other families that if they think something is wrong, to keep chasing and follow your instincts as a parent.”


  3. Courageous siblings Connie and Joe Elson are battling the rare and incurable genetic condition metachromatic leukodystrophy.

    Over the last 18 months, this cruel disease has seen the fun-loving, intelligent and witty Connie become totally dependent at age seven.

    Connie’s symptoms began at age five-and-a-half when the very bright little girl started to display a lack of concentration and clumsy behaviour.

    The progression of the life-limiting disease has been swift and Connie can no longer walk or talk and requires a feeding tube.

    Despite the aggression of the disease, Connie keeps a huge smile on her face.

    Connie and Joe’s parents, Nicola and Ian, are both carriers of the recessive gene and their children had a one-in-four chance of having the disease.

    Joe, five, was also diagnosed with the condition, but at a pre-symptomatic stage he was offered pioneering treatment in Italy as part of a clinical trial.

    Unfortunately Connie’s condition is too progressed for this.

    The family, from Cark, spent four months in Italy for Joe to have ground-breaking gene therapy treatment.

    He had a bone marrow transplant which involved chemotherapy and six weeks of isolation in the foreign hospital over last Christmas and into the new year.

    Joe, a pupil at Allithwaite CE Primary School, is only the 15th child in the world to have this treatment and it is working. His family prays that this could be a cure for the disease.


  4. Nearly 100 people showed up to the Sereno Warriors’ second annual benefit auction on Saturday, Nov. 21 to lend their time and money to ease the financial stress of a family whose children are stricken with Metachromatic Leukodystrophy (MLD), an incurable disease demanding heavy medical attention...

    The event, which was held at the Our Lady of Perpetual Help School in Brooklyn, N.Y.,which was held at was held to benefit Salvatore, 11, and Giovanni, 5, Sereno who both suffer from MLD, which affects the ability for the brain to communicate with the rest of their body, according to their mother Lina Sereno.

    Between her and her husband Carmelo Sereno, day-to-day life is a challenge, as the boys are completely dependent on their parents for day-to-day functioning.

    "Our lives are not like most. We cannot just get up and leave the house,” Lina Sereno said. “We are always changing and keeping the boys comfortable.”

    Friends of the Sereno’s grouped together to form the Sereno Warriors, a committee who organizes fundraisers to assist the family. According to Lina Sereno, the group’s name is a reflection of their own strength during rough times.

    “When the boys were diagnosed, my husband and I said we were going into battle because warriors fight and conquer,” said Lina Sereno. “Last year was very overwhelming with a lot of good emotions because we had people from high school, college, people we work with, distant family, people I’ve never met, people that do and don’t know my boys.”


  5. Shock ran through Chuck Cromwell when doctors told him of his son’s diagnosis.

    On Sept. 5, 12-year-old Ben Morrison-Cromwell was diagnosed with metachromatic leukodystrophy.

    “Me and (Ben’s mom) Lisa were both devastated,” Cromwell said. “The last thing I remember hearing was ‘not reversible’ and ‘not curable’ and ‘there’s no treatment for it’ and ‘fatal.’”

    Last Christmas, Cromwell said he started noticing that Ben seemed to be acting immature for his age and not progressing as he previously had.

    “He wasn’t retaining anything at school,” he said. “You’d tell him one thing the one day, and he wouldn’t know it the next.”

    Ben’s motor skills also started to decrease. After having ridden a bike for most of his life, it became a challenge for him.

    For Ben’s 12th birthday in April, Cromwell took him bowling – something he used to love and was quite good at – but he could tell Ben was struggling.

    The Prince Charles Public School student had previously been diagnosed with attention deficit hyperactivity disorder and anxiety. But through testing and many appointments, doctors realized there was more to it, Cromwell said...

    Already Ben is having absence seizures that last only a few seconds, but they’ll continue to worsen until they’re “full blown,” Cromwell said.

    Eventually, he’ll experience paralysis and lose his ability to speak, see and hear.

    While he’s facing some symptoms of the disease, Ben isn’t aware of his diagnosis, and his parents aren’t planning on telling him.

    “He’s just going on regularly as a kid,” Cromwell said. “He’s happy. He’s smiling all the time.”

    Though there is no cure, some of Ben’s symptoms – like his seizures – can be treated.

    Through the Make a Wish Foundation, Ben was able to visit Florida for a week and enjoy it before MLD makes it more of a challenge.

    “That was quite the experience,” Cromwell said. “A once in a lifetime opportunity.”

    For now, Cromwell said he’s taking things day by day, making sure to stay positive for himself and for his son.

    “You want your spirits to be up because you don’t want them to see (you down),” Cromwell said. “You just want them to be happy and enjoy their life as it is day by day.”


  6. Members of the Kawartha Children’s Dance Company have rallied for a Manilla child who was diagnosed with a rare genetic disorder earlier this year.

    The group will be hosting two performances of The Nutcracker this weekend at the Beaverton Town Hall in support of Ella Andrews and her parents, Wes and Melissa.

    Ella loved to dance,” Ms Andrews said.

    “She did ballet last year and still takes part as much as she can…She’ll be onstage for The Nutcracker, sitting in a sleigh.”

    On May 27 -- just days before her third birthday -- the youngster was diagnosed with metachromatic leukodystrophy, a disorder that causes the progressive destruction of myelin sheath (the material that insulates nerves). The subsequent breakdown of communication between the brain and nervous system causes the gradual loss of mobility, speech, vision and the ability to swallow and clear the lungs.

    “It’s a heartbreaking, terrible disease,” Ms Andrews said.

    “There is no cure. The only treatments available are supportive.”

    At this point, Ella is no longer able to stand and sit independently and is losing the ability to speak and swallow.

    “The last few months have been really rough,” Ms Andrews said.

    “There’s been a rapid decline.”

    But there has been at least one highlight.

    Back in August, the Make-A-Wish Foundation of Canada sent the family on a trip to Disney World in Florida, where Ella had the chance to meet some of her favourite characters.

    “She loves the Disney princesses,” Ms Andrews said.


  7. Like many four-year-olds in reception classes across the country, Joe Elson bounds up to his mother Nicola at the end of the school day and happily reels off the day’s highlights. But it is hard for Nicola and husband Ian to enjoy Joe’s stories about his new school without worrying. In fact, as the days go by, they are becoming increasingly anxious. It was at this stage – the first few weeks of the first year of primary school - that Joe’s sister, six-year-old Connie, suddenly started to regress: her efforts to write turned into a scrawl despite the fact she had been writing her own name since she was three. She became clumsy, knocking things over and tripping up, behaving increasingly like a toddler.

    “Connie was very intelligent; she was reading and writing at four and her maths was phenomenal but then when she started school in 2013 things started slipping,” Nicola, a 39-year-old accountant, recalls...

    By a ghastly coincidence, both Nicola and Ian are carriers of the rare faulty gene, which means that although they are themselves unaffected, their children had a one in four chance of having the disease. The odds of two carriers becoming a couple like Ian and Nicola are one in 10,000. The odds of a child having the type of MLD Connie has is just one in 160,000.

    But the Elsons had more to cope with than their grief and shock over their daughter. Tests in July last year showed that Joe also had MLD, although so far he shows no signs of the disease. “This disease is a monster,” says Nicola. “It’s a cruel, wicked disease. You’ve got a beautiful, perfect child who gets to five and then they are slowly taken away from you.

    “When doctors told us Joe also had MLD I thought they were wrong. I couldn’t believe in our worst possible nightmare that this had happened again.” (continued)

  8. (continued)But in the depths of their despair, the Elsons found hope. Spending hours researching the disease on the internet, Nicola discovered a groundbreaking gene therapy trial that was being conducted on MLD patients in Italy. As the therapy is only thought to work before disease symptoms occur, Connie was not eligible; but the Elsons realised her brother might benefit. “I felt so guilty that we didn’t get to Italy sooner,” Nicola says.

    At the end of last year they flew to the San Raffaele Telethon Gene Therapy Institute (TIGET) in Milan for their son’s experimental treatment. Designed by Prof Luigi Naldini, director of the institute, it is thought to be the most dramatic gene therapy being used in trials today – and is spearheading a renaissance in “gene fixing” technology...

    The initial progress in gene therapy in the 1990s was followed by a string of tragedies. The first was in 1999, when 18-year-old Jessie Gelsinger from the US died after his immune system had an adverse reaction to the common cold virus, used to deliver genes to correct his liver disease. As a result, all US gene therapy trials were halted and support for the entire industry withdrawn. In the following years, use of a type of virus called the retrovirus to deliver gene therapy to patients for various immune disorders caused nine cases of leukaemia (including one death) and three patients acquired a bone marrow disease. “As well as being devastating for the families, this was a major setback for the whole field,” says Prof Bobby Gaspar, a Principle Investigator at Great Ormond Street Hospital, where one patient involved in a trial of the technology developed leukaemia.

    However, Prof Naldini, who was based in California before coming to Milan in 1999, has spent most of his professional life focusing on ways to remove from killer viruses their “dangerous” properties. He has developed a safe method of using a virus called the lentivirus. Apart from being highly effective at inserting its DNA into our genes, the lentivirus has a unique feature particularly important when treating brain diseases like MLD: unlike other viruses it is capable of infiltrating cells that do not divide, such as those in the brain.(continued)

  9. (continued)“Essentially we took the virus apart and only used part of it,” he explains. “To establish infection the virus must first enter the DNA of the cell. It will then reproduce and it also tries to escape any counter-attack by the immune system. In nature it has evolved with this capacity.

    “To make a good delivery vehicle we only need the first step, so we got rid of many of the other functions of the virus to make it safe.” This involved scientists painstakingly removing the “dangerous” functions, viral gene by gene.

    The first pioneering trial to test whether gene therapy using the lentivirus works began in the spring of 2010 and first enrolled eight children with MLD, but the number was expanded to 20 after preliminary results showed the first group of children treated were able to live normal lives. Naldini’s lentivirus, with the dangerous genes removed, has not caused any adverse effects.

    Joe Elson is among the children who are counting on this potentially game-changing technology. Last December he began his five-day “gene-fixing” treatment. It involved a six-hour operation removing stem cells from his bone marrow, followed by a four-day course of chemotherapy to wipe out his diseased cells and make plenty of room for the new cells to thrive. Meanwhile, in the laboratory, scientists used synthetic DNA to make healthy genes to replace the faulty ones, and injected these into the lentivirus that had been made safe. Joe’s stem cells were then exposed to the lentivirus in the hope it would deliver the corrected genes into the cells...

    “It really was mixed emotions for me because you can see he’s suffering but you know it’s for his good,” says Nicola. On the final day Joe received an infusion of his corrected stem cells.

    “I thought there would be six doctors with a wheelbarrow, hauling in some special medical bag but this tiny bag of precious cells came in,” his mother recalls.

    The momentous event was celebrated by all those involved...

    Naldini’s modified lentivirus is now being used in gene therapy around the world including, says Prof Gaspar at Great Ormond Street, on children with immune disorders.

    As the Elsons pack their bags and head off to Italy for Joe’s nine-month check-up, they know nothing can be taken for granted as the critical protein the corrected gene makes takes between six and 12 months to kick in – and it is vital this happens to prevent the disease progressing. Fortunately, things are looking hopeful. “His six-month check-up showed a good number of the corrected genes in his blood and the crucial protein was also detected,” Nicola says.

    Connie meanwhile attends a special school for severely disabled children, a few miles from the family’s home in the village of Cartmel, Cumbria. She has lost the ability to walk, talk and eat but not, says her mother, her magical smile, despite the stiffness and pain she suffers in her muscles. “She loves going swimming, which helps her, ” says Nicola. “She still understands jokes and laughs a lot. Thank heavens, she actually she seems very happy.”

    See the 12/15/15 10:03 pm comment above.

  10. Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, Baldoli C,
    Martino S, Calabria A, Canale S, Benedicenti F, Vallanti G, Biasco L, Leo S,
    Kabbara N, Zanetti G, Rizzo WB, Mehta NA, Cicalese MP, Casiraghi M, Boelens JJ,
    Del Carro U, Dow DJ, Schmidt M, Assanelli A, Neduva V, Di Serio C, Stupka E, Gardner J, von Kalle C, Bordignon C, Ciceri F, Rovelli A, Roncarolo MG, Aiuti A,Sessa M, Naldini L. Lentiviral hematopoietic stem cell gene therapy benefits
    metachromatic leukodystrophy. Science. 2013 Aug 23;341


    Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease caused by arylsulfatase A (ARSA) deficiency. Patients with MLD exhibit progressive motor and cognitive impairment and die within a few years of symptom onset. We used a lentiviral vector to transfer a functional ARSA gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile MLD. After reinfusion of the gene-corrected HSCs, the patients showed extensive and stable ARSA gene replacement, which led to high enzyme expression throughout hematopoietic lineages and in cerebrospinal fluid. Analyses of vector integrations revealed no evidence of aberrant clonal behavior. The disease did not manifest or progress in the three patients 7 to 21 months beyond the predicted age of symptom onset. These findings indicate that extensive genetic engineering of human hematopoiesis can be achieved with lentiviral vectors and that this approach may offer therapeutic benefit for MLD patients.