Worm therapy

Leeches and maggots have a history of use in medicine - for blood-letting or wound cleaning, respectively (and both have FDA approval for modern medical use). Recent reports have suggested potential usefulness for another creepy-crawly.

Filarial nematode worms are particularly nasty mosquito-borne parasites that take up residence in the lymph nodes. The worm is endemic to many tropical and sub-tropical countries and causes elephantiasis - the enlargement of limbs and genitals (and for guys thinking this doesn't sound so bad, the genitals can get so big that they interfere with regular physical activity. Pictures here), as well as less obvious internal damage. However, areas with high rates of filarial worm infection tend to have lower rates of inflammatory bowel disease, arthritis and other inflammation-caused ailments. This is thought, in part, to be caused by ES-62 - a glycoprotein secreted by the worm that has anti-inflammatory properties.

Scientists in Glasgow are now looking for a way to develop ES-62 into a better, non-heart-attack-inducing, anti-inflammatory.

Don't worry though - I don't think they plan on treating with live worms.

Reading through nonsense

We recently heard a solid journal club presentation about genetic nonsense mutations. Nonsense mutations are point mutations in the DNA sequence that introduce a premature stop (or nonsense) codon and can lead to a truncated protein (or, in many cases, no protein at all as nonsense codons are detected by the presence of exon-junction complexes and the mRNA is degraded). The paper discussed described a drug, PTC124, that is entering the final phase of clinical trials that supresses premature termination and allows readthrough of nonsense codons by the translational machinery and production of a full-length protein.

What does this have to do with cancer? The paper discusses the therapeutic potential of the drug in terms of cystic fibrosis and muscular dystrophy - two diseases with pathology known to be caused (at least in some cases) by nonsense mutations in specific genes; CTFR for cystic fibrosis and dystrophin for muscular dystrophy. An obvious target for cancer therapeutics is p53. The p53 gene is mutated in over 50% of human tumours and of those mutants, almost 8% are nonsense mutations (source:IARC p53 mutation database). Research has shown that reactivation of p53 has therapeutic potential in mouse models of cancer, leading to growth arrest and regression of tumours. One need not limit this idea to p53. Nonsense mutations in many other genes, such as BRCA or Rb, have been associated with cancer and bypass of nonsense-mediated decay represents an interesting area to explore when dealing with cancer, and other, therapeutics.

Embryonic Stem Cells (tm) by Invitrogen

Caught a great talk today at the OHRI by visiting speaker Mahendra S. Rao, who is probably the world's leading scientist in embryonic/neural stem cell therapies. The talk featured an overwhelmingly impressive wealth of data on neural stem cell biology, particularly pertaining to transplant studies. Most of this work was done in his former capacity as head of the NIH's stem cell program.

What was most interesting about the talk was the work Rao is now leading as VP Stem Cell research at Invitrogen Corp (in the more ES-cell research friendly state of California). He recently took up this post after leaving the NIH as a result of their decision to abandon ES cell research in light of the Bush administration's strong anti ES cell research policies. From what he presented of his new project at Invitrogen, it's obvious they are now about to kick some serious ass in the arena of clinical therapeutic development. They've got GMP-friendly, FDA-approved and production-scalable technologies and ES cell lines ready to go. Couple with that Invitrogen's recent moves that has established the company as the leader in gene expression and cell culture technologies, and what you have is imminent domination of the biological therapies scene. Looks like one of the first applications they will go after is Parkinson's disease, using ES-derived neurons to replenish dopamine producers in the substantia nigra.

Interestingly, while transplanted ES-derived neurons are suitable for applications such as Parkinson's as they can survive long-term in recipient's brain, Rao mentioned that their potential in other regenerative therapies is limited by the fact that we do not yet know how to make the transplanted cells properly integrate into existing neuronal circuitry. Strong impetus for a lot of interesting research in probing neural connectivity...