Childhood neurodegenerative disorder discovered in monkeys
New York : Scientists have discovered a naturally occurring disease in monkeys that mimics a deadly childhood neurodegenerative disorder in humans that could accelerate development of new gene therapies.
Batten disease is the common name for a broad class of rare, fatal and inherited disorders of the nervous system.
Using genetic analysis, a team from the Oregon Health and Science University (OHSU) in the US, confirmed that a small population of Japanese macaque monkeys carry a mutation in the CLN7 gene that causes one form of Batten disease.
The disease affects the function of organelles within cells called lysosomes, which normally break down waste products much like a cellular garbage disposal.
But when the CLN7 gene is mutated, lysosomes produce a broken form of a protein involved in waste disposal. This causes a buildup of "junk" material in lysosomes, which eventually leads cells to become sick and degenerate.
"The discovery of this non-human primate model of Batten disease will advance our ability to develop and test a gene therapy strategy to replace the normal version of the protein that is missing in this disease," said lead author Jodi McBride, Assistant Professor at the OHSU School of Medicine.
Most forms of the disease begin in childhood and eventually, the affected children become blind, wheelchair-bound, bedridden, unable to communicate and lose the majority of their cognitive functions. These children typically succumb to this fatal disease in their teenage.
"This disease really affects the entire brain, with the cerebellum and cortex showing particular vulnerability," McBride said, in the paper published in the journal Neurobiology of Disease.
In 2007, the first neuronal stem cell transplants in human patients was performed as part of a clinical trial to treat Batten disease.
"We've confirmed 12 Batten disease cases in the colony to date, four of which are young affected monkeys that will enable the development and testing of much-needed treatments for the disease. Additionally, we have identified 28 other macaques in the colony that are carriers of the mutated CLN7 gene," added co-author Betsy Ferguson, Associate Professor at OHSU's School of Medicine.
Human clinical are estimated to occur within the next five years, the researchers said.