Lorenzo's oil got upgraded to stem cell research

Have you seen the 1992 movie Lorenzo's oil? The film portrays the true (and sad!) story of Lorenzo Odone, who, at age 6, was diagnosed with adrenoleukodystrophy, one of the most common forms of leukodystrophies, a family of degenerative diseases that affects the growth of the myelin sheath. Myelin wraps around nerve fibers creating a fatty covering that increases the speed at which impulses propagate. Leukodystrophy is a genetic disorder caused by mutations in the genes that code myelin proteins. When myelin is defective, or not produced in sufficient quantities, it starts degrading, causing the progressive loss of signaling along the nerve. Eventually, the nerve dies.

As shown in the movie Lorenzo's oil, Lorenzo's parents refused to accept the common prognosis they were given at the time for their son (progressive paralysis and death within 2-3 years). Their determination led them to discover an oil mix able to alleviate the symptoms of the disease.

Two papers published in Science Translational Medicine now show that stem cell therapy can partially regenerate neurological function.

Uchida et al. [1] show that stem cell transplantation is effective in the regeneration of the myelin sheath in mouse models. The researchers transplanted human central nervous system stem cells (HuCNS-SCs) into the brains of mice with defective myelination in the central nervous system. The transplanted stem cells generated functional myelin in the mice's central nervous system

In the same issue, Gupta et al. [2] describe how they transplanted the same cells (HuCNS-SCs) into the frontal lobe of four young boys that were affected by Pelizaeus–Merzbacher disease (PMD), a form of leukodystrophy. The transplant was followed by a 9-month regimen of immunosuppression to minimize the chances of rejection. One year after the transplant, magnetic resonance imaging (MRI) showed that the transplanted cells had engrafted and successfully myelinated brain cells. The researchers conclude that "modest gains in neurological function were observed in three of the four subjects. No clinical or radiological adverse effects were directly attributed to the donor cells."

Sadly, Lorenzo died in 2008, one day after his thirtieth birthday. His story, though, was and still is an inspiration to many.

[1] Uchida, N., Chen, K., Dohse, M., Hansen, K., Dean, J., Buser, J., Riddle, A., Beardsley, D., Wan, Y., Gong, X., Nguyen, T., Cummings, B., Anderson, A., Tamaki, S., Tsukamoto, A., Weissman, I., Matsumoto, S., Sherman, L., Kroenke, C., & Back, S. (2012). Human Neural Stem Cells Induce Functional Myelination in Mice with Severe Dysmyelination Science Translational Medicine, 4 (155), 155-155 DOI: 10.1126/scitranslmed.3004371

[2] Gupta, N., Henry, R., Strober, J., Kang, S., Lim, D., Bucci, M., Caverzasi, E., Gaetano, L., Mandelli, M., Ryan, T., Perry, R., Farrell, J., Jeremy, R., Ulman, M., Huhn, S., Barkovich, A., & Rowitch, D. (2012). Neural Stem Cell Engraftment and Myelination in the Human Brain Science Translational Medicine, 4 (155), 155-155 DOI: 10.1126/scitranslmed.3004373