Gene therapy directed straight to the brain works in mice

Scientists revealed an innovative method which can be used to transplant blood-forming (hematopoietic) stem cells directly into the brain. The technique may provide a quicker and more effective way of treating diseases of the central nervous system compared with the standard, indirect mode of delivery.

The technique, reported in Science Advances, involved transplanting donor-derived hematopoietic stem cells (HSCs) directly into the lateral ventricles of the brain, from where they could deliver therapeutic molecules to affected tissues.

Researchers in the USA and Italy used a mouse model of a lysosomal storage disease, a group of metabolic disorders affecting the central nervous system. The disease causes a build-up of material which leads to neurodegeneration.

Until now, the HSCs were administered intravenously and affected the brain indirectly through bone marrow engraftment, a process where stem cells make their way through the bloodstream to the bone marrow and start producing new blood cells. This process is slow and can be inefficient in treating disorders where fast action is required.

'The main issue with the conventional HSC transplant strategy has been the length of time needed for the therapy to take effect in the brain,' said study lead Dr Alessandra Biffi, at the Dana-Farber Cancer Institute, Boston Children's Hospital in Boston, Massachusetts. 'It can take up to a year for the genetically-engineered cell lineage to proliferate, spread and produce therapeutic effects in the brain—oftentimes, patients don't have the luxury of time to wait.'

The HSCs transplanted directly to the brain showed faster effects than the HSCs administered intravenously. The transplant led to more rapid generation of new myeloid cells, which help to decrease the build-up of the excess material responsible for the damage to the nervous system.

Importantly, the donor-derived cells showed the same characteristics as cells of healthy animals. The transplanted cells were also detected in the brain only and not in the other parts of the central nervous system.

The team hopes the work could pave the way for prevention and treatment of lysosomal storage diseases as well as other neurodegenerative disorders such as Alzheimer's or Parkinson's.

Although the method may seem too invasive to be used in humans '[the treatment] would be in line with currently-used clinical procedures that enable access to the brain for treatment' said Dr Biffi.