Molecule developed to kill leukaemia in mice

A designer molecule which is able to destroy a form of leukaemia in laboratory mice and prevent the cancer's spread has been developed by a research group in Japan.

The findings, which are published today in the journal Nature, raise hopes that a similar approach may be possible in human patients.

The molecule was able to kill off abnormal cells and prevent them spreading to other tissues, according to the researchers from the Institute of Medical Science at the University of Tokyo and the National Institute for Advanced Interdisciplinary Research at Tsukuba Science City, Japan.

Earlier work had shown that the molecule, a ribozyme, could destroy chronic myelogenous leukaemia (CML) cells in culture. This latest work indicated that the ribozyme could also be used to treat the disease in mice.

A ribozyme is made of RNA, a nucleic acid related to DNA, but which can also act like an enzyme - a protein that helps to make reactions happen inside cells. The researchers, who preferred to call their discovery a "maxizyme", produced a molecule that "chopped up" essential substances inside the leukaemia cells, causing them to go into spontaneous cell death.

The researchers said their maxizyme worked "with exceptional efficiency" in their animal models, adding, "We find that this ribozyme completely inhibits tumour cell infiltration in these mice."

Two groups of mice were injected with CML cells but only one group was given the maxizyme. All of those which received the designer molecule appeared healthy, whereas those that did not all developed severe leukaemia and secondary cancers.

The maxizyme is a complex molecule which has two "sensor arms" that can recognise abnormal RNA produced by the leukaemia cells. When the two arms identify their target, the molecule changes shape and works to break the abnormal RNA. The CML cell then self-destructs.

CML in humans is usually treated by marrow transplantation, which must be preceded by the complete destruction of the patient's own diseased marrow. Only about half of all CML patients can receive this treatment, however, because of limited marrow donor availability and age restrictions.

"Our results raise the possibility that this maxizyme could be useful for purging bone marrow in cases of CML," which could help to reduce the incidence of disease relapse, they added.