Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Nature’

It’s a fact of human life that we lose physical and mental function as we get older. In the information age that we currently live in, this translates into a decline in our ability to function and perform the activities of daily living. Can we halt or delay age-related memory loss?

Min Wang and colleagues from Yale University School of Medicine in the August 11 issue of Nature, have published some elegant research that suggests we may be able to, at some point in the future.

It’s important to distinguish the cognitive loss associated with normal ageing from that associated with dementias such as Alzheimer’s disease where major changes to the brain structure and function occur. The Yale researchers accomplished this by using aged monkeys that have a highly developed prefrontal cortex (PFC), the part of the brain associated with working memory. Monkeys, unlike humans, do not develop age-related dementias!

Working memory that allows you to keep things “in mind” e.g. where you put the car keys down, relies on a network of pyramidal neurons in the dorsolateral PFC that excite each other.

The strength of this excitatory network depends on the neurochemical environment e.g. elevated cAMP signaling reduces nerve firing. Wang and colleagues reversed the age-related decline in PFC activity by restoring an optimal neurochemical environment. Through a series of experiments they found that:

The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels.

These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.

This research, although preliminary and based on animal models, is promising. It offers the hope that in the future we may be able to reverse or slow-down the age-related memory loss and cognitive defects we would otherwise experience.

Many biotechnology and pharmaceutical companies are focusing on Alzheimer’s disease as a target. What this research suggests is that developing therapies that may delay or slow-down age-related memory decline could also be a valid target for drug development, with a significant market opportunity.

ResearchBlogging.orgWang, M., Gamo, N., Yang, Y., Jin, L., Wang, X., Laubach, M., Mazer, J., Lee, D., & Arnsten, A. (2011). Neuronal basis of age-related working memory decline Nature, 476 (7359), 210-213 DOI: 10.1038/nature10243

There is a lot of buzz this week about Lucentis versus Avastin for the treatment of wet age-related macular degeneration (AMD), something that will be talked about in more detail at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting this weekend in Fort Lauderdale.

Also on the radar at ARVO is more news from Second Sight and their Argus II Retinal Prosthesis (something that I have previously written about on this blog).  For those interested there is a press conference at ARVO on Tuesday, May 3 from 5-6pm.

Second Sight presents updated results from the Argus II Retinal Prosthesis clinical trial, including sentence reading and color vision restoration for previously blind subjects. Two trial participants and independent investigators from the trial will be available for interviews.

Which brings me back to a Nature article published earlier this month that I have been meaning to write about showing, for the first time, the ability to generate a three-dimensional culture of neural retinal tissue from mouse embryonic stem (ES) cells.  A word of warning, you may find the paper a little tough to follow unless you are a scientist in this field.

Eiraku and colleagues from Japan were able to culture retinal tissue similar to that seen in the human eye.  Eye formation starts as an optical vesicle that then develops into a two-walled optic cup.  As the authors note “optic cup development occurs in a complex environment affected by neighbouring tissues.”

What the authors showed in their research was the ability to culture retinal tissue containing ganglion cells, photoreceptors and bipolar cells.  They conclude:

Collectively, these findings demonstrate that the fully stratified neutral retina tissue architecture in this ES-cell culture self-forms in a spatiotemporally regulated manner mimicking in-vivo development.

My take on this research is that it is an important milestone in regenerative medicine that could lead to the prospect of retinal transplants in the future.  I look forward to learning more at ARVO about what the future may hold for retinal transplants derived from human stem cells.

ResearchBlogging.orgEiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., Sekiguchi, K., Adachi, T., & Sasai, Y. (2011). Self-organizing optic-cup morphogenesis in three-dimensional culture Nature, 472 (7341), 51-56 DOI: 10.1038/nature09941

One of the themes of this blog is innovation in biopharmaceutical new product development. Innovation can take many forms ranging from nanotechnology based drug delivery to a novel scientific mechanism of action.  The March 17, 2011 edition of Nature, highlights how innovative preclinical animal models are having an impact on drug development.

In their article on translational medicine, “Cancer lessons from mice to humans”, David Tuveson and Douglas Hanahan, describe how preclinical mouse models helped predict the recent phase III clinical trial results for sunitinib and everolimus in pancreatic neuorendocrine tumor (PNET).

The data was a major breakthrough for this disease. As Sally Church noted on Pharma Strategy Blog, sunitinib doubled the progression free survival (PFS) time and improved OS.

Tuveson and Hanahan in Nature note that “a vast number of potential anticancer drugs are currently in the pipelines of biopharmaceutical companies.” The challenge is not one of a shortage of candidates nor of potential targets, but in deciding which have most promise and where to spend valuable clinical development resources.

The authors conclude that there’s now optimism that genetically engineered mouse models may be able to mimic the progression of human cancer at the cellular and tissue levels. The mouse model of PNET (RIP-Tag2) successfully predicted that sunitinib and everolimus would be effective in treating humans.

Of course, not all human cancers can be modeled and adaptive resistance can subsequently occur in clinical trials, suggesting that preclinical models do have their limitations.

I hope we will see further innovation in mouse models of human cancer as translational medicine develops.

ResearchBlogging.orgTuveson, D., & Hanahan, D. (2011). Translational medicine: Cancer lessons from mice to humans Nature, 471 (7338), 316-317 DOI: 10.1038/471316a

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