Clinical Trials

Synageva BioPharma Corp. has initiated clinical studies to evaluate SBC-102 as an enzyme replacement therapy (ERT) for Lysosomal Acid Lipase (LAL) Deficiency. LAL Deficiency has early and late onset forms commonly referred to as Wolman Disease or Cholesteryl Ester Storage Disease (CESD) respectively, and affects infants, children and adults.

One study will evaluate the safety, tolerability and effect of SBC-102 on growth and survival in infants who have early onset LAL Deficiency (Wolman Disease).  Early onset LAL Deficiency is an autosomal recessive genetic condition and is characterized by profound growth failure, and liver failure and is usually fatal in the first year of life.    

Another study will evaluate the safety, tolerability, and pharmacokinetics of SBC-102 in people who have late onset LAL Deficiency (CESD). Late onset LAL Deficiency is characterized by an enlarged liver, persistently abnormal liver function tests (LFTs) and elevated cholesterol levels. Some patients may also have an enlarged spleen. Many of the symptoms of late onset LAL Deficiency are common to patients with other liver conditions. Untreated, CESD may lead to cirrhosis, liver failure and death.

As LAL Deficiency is rare, Synageva is also conducting Natural History studies to gather more information to better understand the disease.

For more information about the studies for patients with LAL Deficiency, please contact the clinical trials team:  (clinicaltrials@synageva.com or 781-357-9900) or visit www.clinicaltrials.gov (search term “synageva”).

Additional information about clinical trials can be found through the LAL Solace Clinical Trial Page at: http://www.centerwatch.com/trials/default.aspx?OrderID=5792

Getting Tested

A New Test for Lysosomal Acid Lipase Deficiency using Dried Blood Spots

LAL deficiency
Lysosomal acid lipase deficiency (LAL deficiency) is an inherited disorder of the enzyme
acid lipase. The enzyme is contained within a compartment of human cells called the lysosome – so is known as ‘lysosomal acid lipase’. The severe form of the disorder is Wolman disease and results in illness in young babies. Cholesterol Ester Storage Disease presents later in life in older children through to adults and this form of the disorder is more common. Both forms of disorder are probably under-diagnosed with many patients with LAL deficiency going undetected.

Dried Blood Spots
A new test for LAL deficiency has recently become available which allow patients suspected of having the disease to be screened more easily. The test uses a small amount of blood spotted on to a Newborn Screening Card and can be used by the laboratory to test for the enzyme deficiency. These samples are called Dried Blood Spots – or DBS. Newborn Screening Cards are not a new idea. Every baby is tested about six days after birth using Newborn Screening Cards for a number of inherited disorders. The baby has a heel-prick performed and a small amount of blood is put on the card and left to dry. The card is sent to specialised Newborn Screening Laboratories to check for a small number of relatively common inherited disorders – PKU is an example of this.

Current laboratory tests
Until recently, testing for Lysosomal Acid Lipase (LAL) deficiency could not be done using a DBS sample. Traditional tests require a relatively large volume of blood, 5 to 10 mls – the amount required to fill a test-tube. These tests also cause the laboratory a lot of time and effort. Blood samples have to be carefully prepared by extracting white blood cells and the enzyme is measured using the extracted cells. An alternative is to take a skin biopsy from the patient and culture skin cells to perform the test. Again this is a lot of time and effort for the laboratory and the patient has to have a sample of skin taken under carefully controlled conditions.

DBS for LSDs
In the last few years, testing has been developed for a number of Lysosomal Storage Disorders using the DBS sample - Krabbe disease and Taysach disease are examples of these. A scientist from Argentina called Nestor Chamoles pioneered the technique and it has been adopted by laboratories all over the world. There are number of real advantages to using the DBS sample to diagnose this group of diseases. The main advantages are :
A tiny amount of blood is required – a few small drops
When the card is dried the blood is stable and can be used weeks later
Cards can be sent by post to specialised laboratories which may be some distance away – across the world sometimes.
DBS samples do not require complex preparation – simply add water to extract the enzyme
Techniques have been developed which allow testing DBS samples in large batches

The overall result is that testing is cheaper and large numbers of samples can be processed quickly.

DBS for LAL deficiency
Although DBS have been used for other Lysosomal Storage Disorders for some time, until now it was not possible to test for LAL deficiency in this way. The main problem when trying to measure LAL using a DBS sample is the presence of other enzymes which interfere with the test. They have a similar action to LAL which ‘gets in the way’ of the test. Pancreatic lipase is an example of this. This was a difficult technical challenge which had to be overcome. Clinical Scientists at Yorkhill Hospital in Glasgow have overcome the problem by using a new compound in the assay – Lalistat 2. This inhibits LAL but allows its measurement in the presence of other forms of lipase.

Increased testing results in more diagnosis & treatment
The precise details of the new test may be difficult to understand. What is important is the impact DBS testing has on being able to screen much larger numbers of patients who may have the disorder. Tests which are difficult to perform and are expensive can only be done on small numbers of patients – those in whom the Doctor suspects may have a really high chance of having the disease. Tests which are relatively inexpensive and easy to perform can be done more often. It is possible that LAL deficiency may be much common than previously thought. The current estimate is that 1 in 40,000 individuals have CESD. It is most likely that both CESD and Wolman disease have been under-diagnosed and there are many children and adults with LAL deficiency who have not been detected.

The importance of the new test is that screening can be extended to much larger groups of patients who may have the disease - increasing the chance of detection and treatment. The ultimate aim.