HD research news - medical research into treatment & prevention
New strategies for treatment
September 2001
As scientists unravel the mysteries of cell death in HD, they are also achieving impressive results in the search for new treatments. The most exciting highlights of the past several months are the promising
results achieved in the HD mouse using minocycline and creatine.
Under the leadership of Dr Robert Friedlander of Brigham and Woman's Hospital in Boston, investigators explored the therapeutic potential of minocycline in the HD mouse model. Minocycline is an antibiotic,
derived from tetracycline, and is commonly used to treat rheumatoid arthritis, acne, and other ailments. The drug is known to block the production of caspases, suspected of playing an important role in Huntington's disease.
In experiments, Dr Friedlander and his colleagues demonstrated that minocycline was able to block caspase 1, caspase-3, and INOS (inducible nitric oxide synthase). The latter finding is of special interest,
as it offers the first direct evidence that oxidative damage may be important in HD.
It was possible to slow
down the disease process in the mice treated with minocycline - the
treated mice lived for 14% longer than untreated mice. Freidlander notes
that the drug appeard more toxic in the HD mice than the normal mice,
and that extensive study will be needed to determine whether minocycline
could slow the disease process in humans with HD. Nevertheless, it remains
very exciting to note that another promising therapeutic strategy has
emerged, and following safety studies, may be explored through clinical
trials.
Another substance which is already in common use, in this case a dietary supplement, is creatine. It has been suggested that one of the effects of the HD gene may be to repair energy metabolism in brain cells.
Creatine is known to stabilise the energy cycle in cells and may offer protection against apoptotic cell death. In experiments, HD mice treated with creatine showed significant inprovement in survival - up to 20% - and delayed the development of protein
aggregates.
Says Dr Steven Hersch, a participant in the minocycline and creatine studies. "We were very encouraged by these results. It is especially advantageous to have agents such as these to test, which have already
undergone extensive safety and toxicity testing in humans".
The Huntington Study Group is in the planning stages of a phase 2 trial of minocycline in HD patients that will be called MIDAS-HD. Dr Karl Kieburtz is completing a safety and tolerability trial of creatine
in HD patients. Another multicentre phase 2 trial with a focus on biological markers of creatine activity, CREST-HD, has been recently funded by NIH and is in the planning stages under the leadership of Dr Steven Hersch, the principal investigator.
- Acknowledgement: Dr Rod Morrison, Huntington’s Society of Canada, Horizon No 93, Fall 2000
|
