As a so called “orphan disease”, LINCL-Batten disease receives almost NO FEDERAL FUNDING! As close as we are to real treatment for this heartbreaking disease, none of these experimental approaches can proceed without your help and funding.
Within the Federal Government, the focal point for research on LINCL-Batten disease and other neurogenetic disorders is the National Institute of Neurological Disorders and Stroke (NINDS). The NINDS, a part of the National Institutes of Health (NIH), is responsible for supporting and conducting research on the brain and central nervous system. The Batten Disease Support and Research Association and the Children's Brain Diseases Foundation also provide financial assistance for research.
Through the work of several scientific teams, the search for the genetic cause of NCLs is gathering speed:
In September 1997, scientists at the Robert Woods Johnson Medical School and the Institute for Basic Research, NY, announced the identification of the gene for the “classic” Late Infantile form of Batten disease/NCL. The gene, CLN2, is located on chromosome 11.
Identification of the specific genes for Infantile, Late Infantile, Variant Late Infantile and Juvenile Batten disease/NCL has led to the development of DNA diagnostics, carrier and prenatal tests.
Scientists have discovered that the Infantile and Late Infantile diseases are missing key lysosomal enzymes, i.e. Palmitoyl Protein Thioesterase 1 (PPT1) for Infantile and Tripeptidyl Peptidase 1 (TPP1) for Late Infantile. Knowing that these enzymes are missing is now leading to the development of gene replacement, enzyme replacement and stem cell transplantation therapies.
Clinical Trials for Late Infantile Batten DiseaseRecently a phase I clinical trial has been completed:
- Weill Cornell Medical College at Cornell University has completed a phase I safety study using direct intracranial injection of gene therapy vector into the brain. The first clinical study, which involved using AAV serotype II to treat 10 children with LINCL-Batten disease, showed stabilization of the disease in the majority of children. Cornell researchers are awaiting approval and funding before proceeding with phase II using a more powerful gene therapy vector.
Additional Treatments Being Researched
Dr. Beverly Davidson at the University of Iowa is also working on a gene therapy protocol. She is using virus vectors for gene transfer to the central nervous system. Her work in a mouse model is encouraging, and we are eager to support her work in the future.
Small Molecule Therapy
Small molecule (drug) therapies are currently being researched. A pilot program to repurpose existing drugs is currently underway due to the efforts of the Jasper Against Batten fund at Cures Within Reach. They are now developing a partnership with the National Institutes of Health to find new clinical applications for already-approved drugs that can help children who have no time to wait. Screening will soon take place on over 3000 different already approved drugs in the government database to find potential beneficial effects that could slow down, or halt the progression of LINCL-Batten disease. Eleven experts in rare childhood, fatal diseases are collaborating to develop assays to screen these drugs. Cures Within Reach will organize and coordinate the venture. This has never been done before on such a large scale with LINCL-Batten disease, and will hopefully help fast-track treatments to children.
Researchers are also trying to discover the mechanism by which chronic activation of glia in the brain, especially astrocytes and microglia, leads to damage of the neurons and progressive neurodegeneration in diseases like LINCL-Batten disease. The overall goal is to utilize knowledge of potentially “druggable” pathways to develop new therapeutics. The normal role of the glia is to cooperate with the neurons to keep the brain operating smoothly. When an injury or change in the brain occurs, the glia mount an inflammation response to fight off the insult and restore the brain to its proper functioning. But in neurodegenerative diseases, the glia are over-activated, producing a state called neuro-inflammation. Neuro-inflammation can lead to nerve cell dysfunction or death, which manifests as dementia. Although neuro-inflammation appears to play a pivotal role in the development and progression of neuro-degeneration, the molecular mechanisms underlying the process and approaches to reduce the neuro-inflammation have received little attention to date from the research community.
Enzyme Replacement Therapy
Enzyme replacement therapies are also in different stages of development. As a previously proven therapy option in other lysosomal storage disorders, enzyme replacement therapy represents so-called “low hanging fruit”. While some obstacles still need to be overcome, we believe that this may be the first therapy to be widely available to children dying from this devastating disease. Noah’s Hope Fund has partnered with the BDSRA to fund future research into human dosing of an enzyme replacement therapy currently being developed.
You can help save the life of a child with LINCL-Batten disease. Please consider a donation today!