A PROTEIN which helps broken bones and damaged kidneys to heal now looks as
though it may speed the recovery of stroke patients. It works by rewiring the
connections around damaged brain cells. There is also a chance that the protein
may be able to improve memory in Alzheimer鈥檚 patients.
鈥淚t looks very encouraging at this point,鈥� says Marc Charette of Creative
BioMolecules in Massachusetts, the company that is developing the protein. 鈥淭he
region of the brain that鈥檚 damaged dies, but the protein rewires the circuitry
around the damage, through tissue surviving the stroke,鈥� he says.
The experiment, reported in NeuroReport (vol 9, p 1441), used rats
in which the researchers had induced strokes. Osteogenic protein-1 (OP-1) was
injected into their brains and it quickly helped them to recover lost movement
in their limbs. OP-1 has already proved its ability to help bridge gaps between
broken bones (New 杏吧原创, Science, 18 December 1993, p 20) and
Creative BioMolecules is now close to having the procedure approved by the US
Food and Drug Administration. The company is also progressing with work showing
that OP-1 helps to heal damaged kidneys
(Technology, 25 May 1996, p 25).
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The substance, a member of a family of proteins called transforming growth
factor-&bgr;, seems to orchestrate the repair of several types of tissue. The
company has established that OP-1 directs primordial stem cells to differentiate
into tissue that matches the damaged tissue.
When the company discovered that OP-1 triggers the growth of tendril-like
projections on neurons, called dendrites, it decided to test the protein鈥檚
potential for brain repair after strokes.
鈥淒endrites receive signals from other neurons,鈥� says Charette. 鈥淭hey behave
like a switchboard, so you can rewire around the damage.鈥�
To test OP-1 in rats after artificially-induced strokes, Charette and his
colleagues from Massachusetts General Hospital and Harvard Medical School
injected it into the cisterna magna, a brain cavity containing cerebral
fluid.
Through tests which measured how easily the rats could place their limbs on a
nearby platform, the researchers proved that rats on the higher dose鈥�10
micrograms鈥攔ecovered faster than those on the 1 microgram dose
(see Graph).
All the rats receiving OP-1 recovered far faster than those in the control group.
He points out that other substances which repair neurons鈥攕uch as nerve
growth factor and basic fibroblast growth factor鈥攈ave been shown to repair
axons, the fibres that transmit nerve signals. But OP-1 is the first protein
that seems to repair dendrites. In Alzheimer鈥檚 disease, dendrites that are vital
to memory are destroyed, so the company is conducting experiments on rats to see
whether memory can be improved through the use of OP-1.
Charette says it may be possible to begin clinical trials in a year鈥檚 time,
once safety and toxicological tests on animals have been completed.