A Clinical Trial for Juvenile Batten Disease
by David Pearce, Ph.D.

Background

Batten disease, a childhood neurodegenerative disorder results from mutations in the gene known as CLN3. At present, we are only able to treat the symptoms of Juvenile Batten disease. Thus, there is a real need to intervene and slow the progression of this disease. Research has shown that patients with juvenile Batten disease and a genetically similar mouse, known as the CLN3 knockout mouse, that serves as a model for the study of this disease both have an abnormal immunological response. This abnormal immunological response suggests that something happens to the immune system that can result in the immune system literally turning on the patient in much the same way a virus would be attacked, except that the patient's own proteins are targeted. It is proposed that this “autoimmune response” contributes at least partially to cause of juvenile Batten disease. Therefore, a research strategy to block this autoimmune response has been tested in the CLN3 mice.

Two strategies were used to block or “immunosuppress” the immune response in the mice. First, the CLN3 mice were altered genetically to be unable to generate B-cells that produce the autoantibodies, and secondly the CLN3 mice were given a daily dose of the drug, Mycophenolate Mofetil (CellCept), that suppresses B-and T-cell production. For both strategies, CLN3 mice were monitored for a decline in a basic neurological motor function test. Remarkably, genetic and drug induced immunosuppression slowed the decline in motor or physical function in the CLN3 mice.

Significance

The use of Mycophenolate Mofetil (CellCept) is the FIRST demonstration of a reduced disease state in the CLN3 mice. This strategy is not a symptomatic treatment. While we have shown that a decline in motor function in the CLN3 mouse may be slowed, Mycophenolate Mofetil (CellCept) was chosen to target the disease itself.

What's next?

While we have shown that immunosuppression strategies slow the decline in motor/physical function in the CLN3 mice, we need to examine in more detail other aspects of declining neurological function in juvenile Batten disease. This will provide a greater understanding of the treatment strategy as well as provide further details on how broadly this approach will impact disease progression.

NEVERTHELESS, the use of Mycophenolate Mofetil (CellCept) is the first demonstration of a reduced state of disease in CLN3 mice. Mycophenolate Mofetil (CellCept) is used as an immunosuppressive agent in organ transplants in children and is therefore approved for pediatric use as data indicates an acceptable level of side effects in children with a life threatening disease. Therefore, due to the nature of juvenile Batten disease it is reasonable to plan a clinical trial that will test the effectiveness of Mycophenolate Mofetil (CellCept) as a treatment for juvenile Batten disease.

How?

The Batten Center at the University of Rochester Medical Center has the infrastructure in terms of expertise in juvenile Batten disease to perform a clinical trial. However, the design of a trial that will test whether a drug successfully treats a disease requires expertise of individuals who have performed prior clinical trials. Planning and meeting regulatory requirements will require many hours and funding for both design and implementing this trial.

Design and initiation of this trial will require additional support estimated to be in the range of $500,000.