As you can see, we have redesigned the website and plan to update it much more frequently. A lot of exciting and positive events are happening in the search for a cure, but first an update on the boys.
Nathan and Dillon
At the beginning of the year, Nathan caught a very bad cold which caused his body to become much more rigid and spastic – some of his muscles, particularly his neck and arms, were constantly contracted. As a result, Nathan began to have difficulty swallowing and in a very short period of time lost a considerable amount of weight.
To assist his body and to help his muscles relax, we decided to have him injected with Botox in specific areas. This combined with some new medication drastically helped his body.
In April, we had a swallow study done to determine if he was aspirating which is caused when juice or food or even his own saliva enters his lungs when he swallows and typically results in pneumonia. The study confirmed he was aspirating so we decided to have a gastronomy feeding tube surgically placed into his stomach so he could receive the proper nutrition and lessen his chances of pneumonia. He was doing great and gaining weight and and then in early June he was admitted to the hospital for acute pneumonia in the lower left lobe of his lungs. He required IV antibiotics and recovered relatively quickly – we stayed at Cedars for 4 days.
He has had more energy and has been more engaged and alert and laughs much more often since the G-tube was inserted as he is now getting the nutrition he really needs. We are all relieved.
Dillon continues to rule the house. He has one speed – run! He is quite pigeon-toed but that does not stop him. He just turned 2 on June 23rd, and we had a small family celebration with lots of balloons, cheeseburgers, presents and cake. He really had a great time and loves to play (bang) on his new piano. He has about 20 word approximations so his speech is definitely delayed but continues to try very hard and goes to speech therapy weekly in addition to school 4 days a week.
The Cure
Below is a progress update directly from the scientists running the gene therapy clinical trials on the cats and the sheep models that we finally have! We did not have animal models until just recently and a farmer found that his sheep have naturally occurring Tay-Sachs which is good luck for us. It is a much larger animal model with a brain size close to a child’s. We need excellent results with the treatment of the sheep. It must go well in order to have a clinical trial for patients in 2011.
In short, the cats that have been treated with gene therapy are unrecognizable from typical cats. They are indistinguishable from normal cats at an age that they should not even be alive. It is amazing.
Tay-Sachs Gene Therapy Consortium Progress Update – March 2010
The performance of AAV-treated GM2 mice in behavioral tests of motor and neurological functions is comparable to that of age-matched normal mice.
In a related project sponsored by Auburn University, University of Massachusetts Medical School and the National Institutes of Health (NIH), a GM1 cat treated by AAV injection is now 6.5 months of age and its behavior continues to be indistinguishable from a normal littermate. Disease onset in this model typically occurs at 3.5-4.0 months of age. Neither the veterinary neurologist that has been following this cat on a regular basis, nor researchers with many years of experience with this cat model are able to identify any signs of disease. A number of AAV-treated GM1 cats are currently in the pipeline.
An AAV-treated GM2 kitten is now 2 months of age and continues to do well. By 3.5 months of age we will know better whether the AAV-injections are having an effect since untreated GM2 kittens by this age are capable of standing but not ambulating. By 2-2.5 months of age untreated GM2 kittens usually display whole body tremor. Another GM2 kitten has been treated in late March, 2010.
Breeding of the GM2 cat colony continues at an accelerated pace to generate GM2 kittens for therapeutic efficacy experiments.
The AAV vectors encoding feline alpha and beta-subunits have been tested in heterozygote (HZ; carriers of one normal and one mutant copy of the gene) GM2 cats and levels of enzyme expression in the brain and cerebellum are up to 60-fold higher than normal at 1 month after injection. Importantly there was no evidence of inflammation.
The Tay-Sachs sheep colony has been very productive and we have now identified four affected lambs born in the last two months. Two affected lambs and age-matched controls will be used to characterize in detail disease progression using a battery of tests to assess neurological function.
We are currently cloning the sheep alpha and beta genes and will produce AAV vectors carrying these genes for injection into affected lambs.
Two affected lambs will be injected with AAV vectors encoding the sheep alpha and beta genes. This experiment is very important to demonstrate the effectiveness of our approach in the only Tay-Sachs disease animal model available that displays a severe phenotype.
The retrospective natural history study is in its final phase. The results of this study will be presented at the annual family meeting of the NTSAD. Prospective studies in LOTS patients are currently underway and studies in infants are in preparation. Both aim to develop biomarkers and validate imaging and clinical scoring scales that will be used to assess treatment effects in the clinical trial.
