Published on November 7th, 2018 | by Mark Mitra


Acute Leukaemia: Promising Results from New Drug

Small molecule therapy is a major area of research in cancer treatment and is transforming treatment from the ‘one size fits all’ approach of chemo-drugs, towards more selective therapy. Small molecule drugs have already been designed and approved to treat specific types of cancers. One major example of a successful small molecule drug is imatinib or “Gleevec” which inhibits the BCR-ABL protein kinase and is used to treat patients with chronic myeloid leukaemia (CML). The results are very positive with minimal adverse effects (see previous article “The Tale of the Philadelphia Chromosome” by Peter Morrice). Imatinib was pivotal in recent pharmacology advances and has proved the effectiveness of designed, selective, small molecule drugs.

However the treatment for Acute Myeloid Leukaemia (AML), which is the most frequent type of leukaemia in adults, has barely changed over the last forty years with treatment consisting of chemotherapy. The prognosis is poor with only a 25% survival rate after five years in adults. In August 2018, Yinon Ben-Neriah and his team from The Hebrew University of Jerusalem published their recent research into developing a new drug A51, an alpha series inhibitor, that uses small molecules to treat AML with promising results. The advantage of using multipurpose targeting drugs instead of a single focused targeted treatment means resistance to small molecular drugs is highly unlikely in leukemic cells. A51 works by having multiple effects on different cell proteins simultaneously, acting like a cluster bomb attacking different protein pathways preventing the CML cells from evading the drug therapy. In addition the researchers found that this new drug activated the tumour suppressant gene P53.

Trial Results and Challenges

From laboratory experiments, A51 performed well against various types of human AML cells including an aggressive form of human secondary leukaemia which was injected into mice. Administration of A51 into mice resulted in a 50% survival rate 160 days after being inoculated with AML cells.
Finding a therapeutic window for a drug is of great importance as it represents the concentration dose at which there is a therapeutic response with few adverse effects. Administering one drug, instead of a cocktail of drugs which target specific areas, is hoped to reduce the side effects of cancer treatment. Trial results of this new drug showed that the mice had no adverse side-affects at therapeutic doses of 5-10 mg/kg/day and an oral dose of A51 at 20 mg/kg revealed the drug was very well absorbed in the gastro-intestinal tract of mice. At these low doses, the A-inhibitors were shown to be are selectively affecting leukemic cells and not affecting normal functioning cells.


These results are promising and prove the potential benefit of small molecules in treatment of human AML. A51 has shown to have good absorption rates with minimal side effects. Compared to chemo- drugs, A51 can effectively destroy CML cells without excessive damage to normal functioning cells. At the end of summer 2018, the company ‘BioTheryX’ applied to the Food and Drug Administration in the US to commence phase I clinical trials for the Alpha inhibitors. If approved they hope to start the trials 2019. However, further research needs to be conducted to measure the drug’s effectiveness and toxicity in humans and it will take 2-3 years of trials before the drug could become commercially available. This type of drug could potentially also be revolutionary in the treatment of some cancers such as lymphomas and melanomas.

Featured image from Pixabay (CC0).

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