Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector

As discussed beforehand, ALD is a disease deficient in the ALD protein, an adenosine triphosphate-binding cassette transporter encoded by the ABCD1 gene involved in fatty acid degradation.  Researchers have found a novel way to replace this dysfunctional gene with the wild-type by using meas of gene therapy. Many of the therapies for ALD today involve bone marrow transplantation. The long-term benefits of bone marrow transplantation are mediated by the replacement of brain microglial cells derived from donor bone marrow myelo-monocytic cells. Unfortunately, bone marrow transplantation carries a high risk of mortality and it can be expecially difficult to find a matched donor. Researchers introducing gene therapy has reasoned that hematopoietic stem cell gene therapy can be a more appropriate therapeutic alternative.

In this therapy, CD34+ cells were removed from two patients and a lentiviral vector encoding the wild-type ABCD1 gene was infused into the hematopoietic cell and then reinfused back into the patients. An HIV-derived vector was used to deliver the therapeutic gene into patients cells.

After 24 to 30 months, there was a detected polyclonal reconsitution with 9 to 14% of granulocytes, monocytes, and T and B lymphocytes expressing the ALD protein.

In the graphs protrayed above, there is an increased percentage of lymphocytes/monocytes, and CD+ cells expressing the ALD protein. There is also a decreased concentration of C26:0/C22:0 fatty acids after gene therapy.

14 to 16 months after infusion, MRI scans show progressive demyelination stopped as depicted below.

Nevena V

References:

http://www.sciencedaily.com/releases/2009/11/091105143706.htm

Cartier N. et al. (2009) Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-linked Adrenoleukodystrophy. Science 326: 818-823.