The first hematopoietic stem cell transfer (HCT) for cerebral X-linked adrenoleukodystrophy (X-ALD) was performed in 1982, with long-term results.
Leukodystrophies are a group of diseases that result form defects in lysosomal enzymes. The lysosomes are small subcellular organelles discovered about 60 years ago by the Belgian cytologist Christian de Duve; they contain acidic hydrolases (pH ~4.5), enzymes by which lysosomes exert their function in recycling molecules from cellular debris, aged organelles, bacteria, viruses and waste compound. Deficiency of a lysosomal enzyme causes the blockage of the corresponding metabolic pathway, leading to the accumulation of its indigested substrates.
Approximately 40 known lysosomal storage disorders cumulatively affect 1 in 5,000 births. Signs and symptoms of the pathology are related to the entity of substrate accumulation and sensitivity of the cell to the abnormal storage. A general principle behind stem cell or gene therapies is that successful engraftment will provide a source of the missing enzyme for the life of a patient. HCT has been used for decades to cure or arrest several neurodegenerative lysosomal storage diseases. Despite significant progress, HCT is still associated with risks of graft failure or graft-versus-host-disease, and there is strong interest in identifying optimal treatment variables.

Epileptogenesis is the process by which a normal brain becomes epileptic. Epilepsy is a disorder of brain function expressed as the periodic and unpredictable occurrence of seizures. The term seizure denotes a fleeting change of behavior caused by the disordered, synchronous, and rhythmic firing of populations of neurons. It is currently unknown if antiseizure drugs in clinical use have any prophylactic value in preventing the development of epilepsy or epileptogenesis.
Mesial temporal lobe epilepsy (MTLE) is the most common form of partial epilepsy. Up to two-thirds of MTLE patients exhibit a history of complicated febrile seizures, preceding the emergence of MTLE. In many cases, as a consequence of these febrile seizures, the hippocampus becomes sclerotic (Ammon’s horn sclerosis), an alteration frequently associated with MTLE. It is therefore thought that some cortical electric alterations induced by fever lead, in the short term, to hippocampal sclerosis and, in the long term, to MTLE. Research into mechanism by which “seizures beget seizures” has identified some therapeutic targets that could prevent the progression to epilepsy, including the mammalian target of rapamycin (mTOR) and the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway. Some members of BM&L-International Society of Neuroscience are particularly interested in studying BDNF-TrkB pathway, which has been implicated in numerous animal studies. TrkB activation is considered pro-epileptogenic, because mice lacking of TrkB in forebrain neurons are unable to undergo epileptogenesis in the kindling model of the process.
For these reasons it is thought that selective inhibitors of TrkB may be effective anti-epileptic agents.