Each year, a handful of New Zealand children are affected by Batten disease, which reduces its victims, slowly, to a vegetative state and, eventually, kills them. Shane Gilchrist discusses hope and loss with two people at the coal-face of the disorder.
It was Ra Timms' 42nd birthday when she and husband Mark received a letter from a specialist predicting an ''horrific'' future for their 10-year-old daughter, JordynRose.
The couple were used to bad news. Several years earlier, they had visited another specialist at Timaru Hospital, following concerns about their son, Brad. After examining the 5-year-old, the doctor commented, ''oh, you poor little boy''.
The prognosis on both occasions: JordynRose and Brad had Batten disease, a neurodegenerative condition likened to a combination of Alzheimer's, Parkinson's, epilepsy and blindness.
The result, by differing degrees, is a steady decline to a vegetative state and, eventually, death.
''You look back on those moments and think they are easy compared to what we went through. The journey our daughter went through ... if I could take away what she went through ...'' the 54-year-old mother trails off.
It's little wonder Mrs Timms pauses, having borne witness to a disease that took JordynRose slowly, painfully, ''in bits and pieces'', until she died on August 7, 2012, aged 19.
''We know we must walk a similar path with our son, and so it begins,'' Mrs Timms says of Brad, who turns 25 in December.
Each year, on average, four New Zealand children are affected by Batten disease, which is the result of a genetic malformation that causes the absence of a particular protein in the brain.
There are four main types of Batten disease, including an even rarer form that strikes adults.
The more common forms become apparent around the age of 3-4 and about ages 8-10, when children may become clumsy and start having seizures.
In all cases they go blind.
Yet a flock of Canterbury sheep - and some potent scientific research - could offer a glimmer of hope.
University of Otago biochemist Dr Stephanie Hughes and her laboratory team have been modifying viruses in a process known as gene therapy.
Then, in collaboration with a Lincoln University team led by Prof David Palmer, these viruses have been used to treat sheep that have Batten disease.
Simply, it uses a virus to do what it does best: attack cells in the human body and attempt to introduce its genetic material to the host cell.
Infused with the corrected copies of two genes (CLN5 and CLN6), the virus was injected into the cells of sheep affected by two naturally occurring forms of Batten disease.
CLN5 and CLN6 genetic mutations cause similar late-infantile forms of Batten disease. However, the proteins (or factors) missing in these two forms have vastly different functions, both largely unknown.
All six CLN5 Batten disease-affected sheep that underwent gene vector therapy showed no signs of ill health or disease.
In short, the gene therapy prevented the disease.
In contrast, the untreated CLN5 sheep deteriorated at the predicted rate.
It should be emphasised, however, that only one of the six sheep with CLN6 Batten disease showed signs of improvement.
Still, the findings are significant, not only for the research community both in New Zealand and around the world, but for families and children living with Batten disease.
According to CureKids, which in 2012 provided $100,000 for the research project between University of Otago and Lincoln University, the direct financial costs for families can be up to $100,000 per year.
Many parents leave their jobs to become full-time carers.
Dr Hughes says she and her fellow researchers have learned much from the experiences of New Zealand families dealing with Batten disease.
''We had a meeting at Lincoln a couple of weeks ago. It was a really good way for scientists to get to meet the families, who know what the kids go through every day. They give us clues as to what might be happening with the disease.
''For instance, several years ago I found out from one parent that these kids have hallucinations. If I hadn't talked to the family, I wouldn't have known.
''The families are amazing,'' Dr Hughes says.
• In some cases, it takes years before Batten disease is correctly diagnosed.
Seizures might be mistaken as epilepsy; if blindness is the first sign, it could be blamed on another inherited condition.
Mrs Timms says both her children were initially diagnosed with Stargardt's disease, a degenerative eye condition.
However, other symptoms prompted her to continue looking for answers.
''Because this is so rare, a lot of specialists and doctors didn't know about it,'' Mrs Timms says.
''Even though both our children had juvenile Batten disease, each was quite different. Brad became clumsy and angry, JordynRose moody and socially inactive,'' Mrs Timms says, adding JordynRose was affected far more greatly than Brad.
''As a teenager, Brad's symptoms had more to do with his behaviour. The chemicals in his brain were imbalanced. Batten disease is a neurological disorder. When part of your brain is dying, of course, that is going to mess with a lot of things.
''Within juvenile Batten disease, there is a whole realm of behavioural issues. Children are often misdiagnosed with ADHD, conduct disorder, Asperger's ... you name it, we've had it thrown at us, including bad parenting.
''JordynRose would have multiple seizures a day. A lot of people don't realise but there are different types of seizures. Hers were pretty big. These increased over the years. She lost her mobility and her limbs became contorted.
''Imagine how a ballet dancer points her toes. Well, imagine that foot going way beyond that, pointing downwards. The pain that would come with that ... we'd massage her for two or three days straight. We'd give each other breaks or the support workers would. None of the drugs touched it.''
Mrs Timms says Brad's seizures and hallucinations have increased.
He is transitioning to a wheelchair and his speech has become hard to decipher.
Still, his personality remains intact.
Her son has an ''amazing outlook'', she says, adding Brad still surprises his parents with ''pearls of wisdom and astounding facts''.
''It is a cruel disease. You experience the complete spectrum of emotions. Jordy was 19 when she passed away, three years ago. Brad will be 25 in December.
''Many families have had children before one is diagnosed. They then have a 25% chance of having another child with the disease.''
Hence Mrs Timms has established a support group, Batten Disease NZ. Yet, given the rarity of the disease, '' there are only four kids in it''.
With the help of a few ''very dedicated'' friends, she has organised fashion shows, charity golf tournaments, made postcards and jewellery that, along with donations, have raised funds for medical and scientific research as well as allowed families to attend overseas conferences.
• Dr Hughes, who has been researching Batten disease for the past 20 years, is not alone in her quest to find a cure.
Scientists from Sydney, Cambridge University and King's College, London, have joined those at Otago and Lincoln, forming the Batten Animal Research Network (BARN).
Many are involved in gene-therapy trials.
In fact, treatment for one form, the most common late-infantile form (CLN2) of the disease has been undergoing human clinical trials for about 10 years.
Which begs the question: when will Dr Hughes and company extend their tests from sheep to people?
''Some people would like to think it will happen next year,'' she says.
''In regards to the form of Batten disease we've had success with, the next step is to see if we can prevent the progression of the disease once the first symptoms have been identified.''
Importantly, Dr Hughes' research could be refined to treat other forms of Batten disease, as well as more than 50 genetically inherited disorders that are characterised by a deficiency of one or more specific lysosomal enzymes.
Found within each of the body's billions of cells, lysosomes break down complex material to simple products. When that ''recycling'' process fails, lysosomal disease occurs.
''Even though Batten disease is rare, we are finding similarities between it and more common disorders such as Parkinson's and Alzheimer's,'' Dr Hughes says.
''Also, these children have a form of epilepsy, so if we can prevent those seizures, the treatment might also be applicable to more common types of epilepsy.
''We are using cells from the sheep to find out if we can find new drugs or new gene therapies to help with other forms of the disease.''
Still, Dr Hughes adds some words of caution.
She notes that although there are more than 1700 clinical trials for various gene therapies under way, just one commercial gene therapy is available to the public.
''Doctors can prescribe therapy for a lipid disorder.
''You have to put your science hat on and not give people false hope.
''That is quite tricky at times, particularly when you become emotionally close to families.''
In regard to the Timms family of Timaru, it's a case of wait and see.
Mrs Timms, who describes herself as an analytical person, someone who learns everything they can about a subject, is aware of overseas gene-therapy trials for the juvenile form of Batten disease, but notes ''there are criteria your child has to fit''.
''They have to be able to walk a certain number of steps and do this, that and the other. The reality is, even if Brad could do that, how would we fund it?
''It's easy for people to say, `oh, I'd sell my house', but how do you live overseas?
''There are lots of things happening in regards to research. But we don't know whether any of this will help our child.
''It is the proverbial carrot dangling.
''And time is not our friend.''
Batten disease, what is it?
Named after the British paediatrician who first described it in 1903, Batten disease is a fatal, inherited disorder of the nervous system that typically begins in childhood.
Also known as Spielmeyer-Vogt-Sjogren-Batten disease, it is the most common form of a group of disorders called the neuronal ceroid lipofuscinoses, or NCLs. Although Batten disease originally referred specifically to the juvenile form of NCL, the term is now used to describe all forms of NCL.
There are four main types of NCL, including two forms that begin earlier in childhood and a very rare form that strikes adults. The symptoms are similar but they become apparent at different ages and progress at different rates. Infantile NCL (Santavuori-Haltia disease): begins between about 6 months and 2 years of age and progresses rapidly.
Affected children fail to thrive and have abnormally small heads (microcephaly). Also typical are short, sharp muscle contractions called myoclonic jerks. Initial signs of this disorder include delayed psychomotor development with progressive deterioration, other motor disorders, or seizures. The infantile form has the most rapid progression and children live into their mid-childhood years.
Late infantile NCL (Jansky-Bielschowsky disease): begins between ages 2 and 4. The typical early signs are loss of muscle co-ordination (ataxia) and seizures along with progressive mental deterioration. This form progresses rapidly and ends in death between ages 8 and 12.
Juvenile NCL (Batten disease): begins between the ages of 5 and 8 years of age. The typical early signs are progressive vision loss, seizures, ataxia or clumsiness. This form progresses less rapidly and ends in death in the late teens or early 20s, although some may live into their 30s.
Adult NCL (Kufs Disease or Parry's Disease): generally begins before the age of 40, causes milder symptoms that progress slowly, and does not cause blindness. Although age of death is variable among affected individuals, this form does shorten life expectancy.
The song
CureKids has partnered with the All Blacks in releasing a collaborative song with the aim of raising as much money as possible to tackle Batten disease.
The song, Team Ball Player Thing, produced by Brooke Howard Smith and Jesse Griffin, with lyrics provided by Kiwi children, is the official All Blacks supporter song.
All funds raised by the song will go to funding research into late infantile Batten disease. Every donor is entitled to download the song at no cost. Alternatively, the song can be purchased through iTunes.
