Progress on Cell-Based Therapies

Spinal cord injury and HIV are the targets of two innovative cell-based therapies, with the planned HIV treatment relying on gene-therapy to produce in vivo RNA interference (RNAi).  In a very short news piece in Nature (subscription required), "Pioneering HIV treatment would use interference and gene therapy", Erika Check writes that;

If the FDA says yes, [John Rossi and his team at  at City of Hope's Beckman Research Institute] will test the therapy on five HIV patients who have a blood cancer called lymphoma. They will treat the patients' lymphoma with aggressive chemotherapy and a bone-marrow transplant — a normal procedure. But before the transplant, they will use gene therapy to add stretches of DNA to stem cells in the bone marrow. It is hoped that molecules encoded by the added genes will trigger the cells' RNAi defences against HIV.

The trial is different from the RNAi trials already under way, because the molecules used in those studies remain in the body for only a short time. The City of Hope researchers will deliver DNA packaged into a gene-therapy vector that could persist in patients for months or even years.

The Recombinant DNA Advisory Committee is having Rossi perform additional safety tests before giving the OK for the trial.  If this works out, it will demonstrate a remarkably powerful way to alter human physiology through the permanent (?) addition of a new RNAi pathway.  The strategy pursued by Rossi, et al., would provide a pool of stem cells that produce lymphocytes immune to HIV.  Since HIV shows some tropism for neural and other tissues, the treatment may not completely rid patients of the virus, but as lymphocytes carrying HIV die out at least the patient would have a source of healthy immune cells.  As this research goes forward, we can expect significant press coverage because the technique will probably find immediate use in treating many other chronic diseases.

The work on repairing spinal cord injury through cord blood cell transplantation has received surprisingly little press.  In an article in Cytotherapy, K-S Kang et al., demonstrate that multipotent stem cells (MSC) derived from umbilical cord blood colonized the site of a spinal cord injury in a 37-year old women who had been a paraplegic for almost 20 years.  The MSCs were amplified in vitro and then surgically transplanted to the site of the injury.

Prior to treatment, the patient showed no somatosensory or motor activity in her lower body, and nerve conduction studies confirmed the extent of the damage.  After transplantation, the patient regained significant sensation within 2 weeks and could maintain an upright posture.  She was able to move her lower legs shortly thereafter.  Nerve conduction studies were used to confirm the extent of recovered electrical activity.  CT and MRI demonstrated regeneration of the spinal cord.

My neurophysiology is more than a tad rusty, which means the import of some specific things reported in the paper isn't immediately clear to me, but the overall results are enough to make anyone take notice; a previously paralyzed patient is now able to at least feel stimulation in her lower limbs, maintain an upright posture unassisted, and has regained some motion in her lower legs.

The specific mechanisms behind the recovery must now be determined, including how the MSCs produce such dramatic improvement.  The authors also note that they cannot rule out the surgery as effecting some recovery.  But the demonstrated increase in electrical activity and motion is extraordinary.  And you have to imagine that the ability to maintain an upright position unassisted for the first time in 20 years is by itself an enormous gift.

This is just one patient, and just one paper, so lots of work is required before anything like this becomes standard treatment.  It is also unclear what the long term effects of the procedure and the new cells will be.  Then there is the little problem that in the U.S. working with stem cells is a tad problematic, regardless of their source.  This study notably, took place in Korea.

Nonetheless, what fantastic news.