Batten disease

Batten disease (also known as Spielmeyer-Vogt-Sjögren-Batten disease) is a rare, fatal autosomal recessive neurodegenerative disorder that begins in childhood. It is the most common form of a group of disorders called neuronal ceroid lipofuscinosis (or NCLs).

Although Batten disease is usually regarded as the juvenile form of NCL (or "type 3"), some physicians use the term Batten disease to describe all forms of NCL. Historically, the NCLs were classified by age of disease onset as infantile NCL (INCL), late infantile NCL (LINCL), juvenile NCL (JNCL) or adult NCL (ANCL).

At least eight genes have been identified in association with Batten disease, but juvenile NCL, the most prevalent form of Batten disease, has been linked to mutations in the CLN3 gene.

Symptoms
Early symptoms of the disorder usually appear around ages 4-10, with gradual onset of vision problems, or seizures. Early signs may be subtle personality and behavior changes, slow learning or regression, repetitive speech or echolalia, clumsiness, or stumbling. There may be slowing head growth in the infantile form, poor circulation in lower extremities (legs and feet), decreased body fat and muscle mass, curvature of the spine, hyperventilation and/or breath-holding spells, teeth grinding, and constipation.

Over time, affected children suffer mental impairment, worsening seizures, and progressive loss of sight, speech and motor skills. Eventually, children with Batten disease become blind, bedridden, and demented. Batten Disease is a life limiting disease; life expectancy varies depending on the type or variation.

History
Batten disease is named after the British pediatrician Frederick Batten who first described it in 1903. Also known as Spielmeyer-Vogt-Sjögren-Batten disease, it is the most common form of a group of disorders called neuronal ceroid lipofuscinosis (or NCLs). Although Batten disease is usually regarded as the juvenile form of NCL, some physicians use the term Batten disease to describe all forms of NCL.

Inheritance and diagnosis


Batten disease is inherited in an autosomal recessive pattern. The mutation causes the buildup of lipofuscins in the body's tissues. These substances consist of fats and proteins and form certain distinctive deposits that cause the symptoms and can be seen under an electron microscope. The diagnosis of Batten disease is based on the presence of these deposits in skin samples as well as other criteria. Eight genes have now been identified that cause different types of Batten disease in children or adults, more having yet to be identified. Two of these genes encode enzymes. The function of most of these genes is still unknown. The identification of these genes opens up the possibility of gene replacement therapy or other gene-related treatments. Batten disease is very rare and occurs in an estimated 2 to 4 out of every 100,000 births in the United States.

Treatment
In June 2004, a Phase I clinical trial was launched at Weill Medical College of Cornell University to study a gene therapy method for treatment of the signs and symptoms of late infantile neuronal ceroid lipofuscinosis (LINCL). The experimental drug works by delivering a gene transfer vector called AAV2CUhCLN2 to the brain. In 2008, it was reported that the procedure, which involved injecting a harmless gene-bearing virus into the brain, is safe; and that, on average, it significantly slowed the disease's progression during the 18-month follow-up period.

In November 2006, after receiving FDA clearance, neurosurgeon Dr. Nathan Selden, pediatrician Dr. Robert Steiner, and colleagues at Doernbecher Children's Hospital at Oregon Health & Science University began a clinical study in which purified neural stem cells were injected into the brain of a six-year-old child suffering from Batten disease, who had lost the ability to walk and talk. This patient was the first of six to receive the injection of a stem cell product from StemCells Inc., a Palo Alto biotech company. These are believed to be the first-ever transplants of fetal stem cells into the human brain. By early December, the child had recovered well enough to return home, and it was reported that there were some signs of speech returning. The main goal of Phase I clinical trials, however, was to investigate the safety of transplantation. Overall, the Phase I data demonstrated that high doses of human neural stem cells, delivered by a direct transplantation procedure into multiple sites within the brain, followed by twelve months of immunosuppression, were well tolerated by all six patients enrolled in the trial. The patients’ medical, neurological and neuropsychological conditions, following transplantation, appeared consistent with the normal course of the disease.