Health,Stem Cells, and Technology

Sunday, March 13, 2011

Japan tsunami: Here's how you can help

Nations are responding to the devastation in Japan, sending aid workers, rescue equipment, and humanitarian supplies. Individuals can help too by donating to legitimate charities, such as the Red Cross.

The devastation in Japan is huge and winter is bringing freezing temperatures to the Miyagi Prefecture, including Sendai. Japan is a peace loving, non-corrupt society )
that has been a good citizen of the world, and deserves our support.

Friday, March 4, 2011

Personalized Medicine: Reverse Engineering Nanomachines For Genetic Repair

I've been writing about personalized medicine for a long time, and indeed my company, BioRegenerative Sciences, Inc. (BRS), is involved in bringing personalized medicine and therapeutics to the marketplace using our core S2RM Technology. A number of people have asked about some of the stem cell technologies in development for therapeutic use and so I wanted to write about one more method that is tied to personalized medicine, namely using nanomachines for genetic editing of stem cells.

A new method is being developed using designer zinc finger nucleases (ZFNs) for genetic repair of cells, including stem cells. These designer zinc finger nucleases are nanomachine for genetic editing. That is, these ZFNs are engineered molecules that can be used to edit the sequence of a gene, doing so to remove and repair sequences of our genes that underlie diseases.

Let’s see how the the ZFNs work. First, the ZFN is constructed to interact with the DNA sequence exclusively where the problematic gene resides. Then the FFNs is introduced into our cells, and in the case of BRS, we introduce the ZFN into extracted stem cells from the patients body in an autologous procedure. Then, when a pair of the engineered ZFNs bind to the DNA in the correct orientation and spacing along the DNA sequence, the DNA sequence is cut between the binding sites of the two ZFNs. The DNA cleavage and subsequent repair only occur when both pairs of the ZFN bind the DNA. The break in the DNA triggers an innate repair process of the cell’s DNA, the cell’s endogenous homologous repair machinery. Harnessing the innate power of the cellular machinery to repair the DNA can be used to induce several outcomes for therapeutic benefit.

First, if cells are treated with ZFNs alone, the repair process often results in the rejoining of the two broken ends of the DNA.  Typically the loss of a small amount of genetic material that results in disruption of the original DNA sequence will result in the generation of gene disruption, that is in a shortened or non-functional protein.  Work at Sangamo BioSciences has shown that ZFN-mediated gene modification may be used to disrupt a gene that is involved in disease pathology such as disruption of the CCR5 gene that codes for C-C chemokine receptor type 5, which HIV uses to enter cells. In this manner, the ZFN procedure can be used  to treat HIV infection by removing the substrate for HIV entry into the cell.
The aforementioned technology can also be extended. For example, if cells are treated with ZFNs in the presence of a donor DNA sequence that encodes the correct gene sequence and substitutes for the dysfunctional gene sequence, the cell can use the donor as a template to correct the cell’s gene as it repairs the cleaved sequence thus resulting in ZFN-mediated gene correction. ZFN-mediated gene correction enables a corrected gene to be expressed in its natural chromosomal context, and may provide an important approach for the precise repair of DNA sequence mutations in stem cells responsible for many diseases,  such as HIV. While this work shows great promise genetic repair of diseases, much more work is required to determine whether a number of potential problems, such as gene stability, result as part of the procedure. However, recent early stage Phase 1 clinical trials by Sangamo BioSciences demonstrate positive results for the technology in the treatment of HIV patients currently on HAART.

Thursday, March 3, 2011

Genetic Mutations Are Common In Reprogrammed Stem Cells

Two studies in Nature from different labs at UCSD have shown that before reprogrammed cells can be used for therapy, scientists need to better understand how reprogramming affects the cells genome. Adult cells that have been reprogrammed into stem cells harbor a number of genetic mutations, some of which appear in genes that have been linked to cancer. Although scientists don't yet know how this might affect the use of the cells in medicine, the findings from Professors Lawrence Goldstein and Kun Zhang show that the cells need to be studied much more extensively. One of the major concerns about stem-cell-based therapies when using embryonic stem cells and iPSCs, but not adult stem cells, has been whether they carry a risk of cancer; because both these types of stem cells and and cancer cells are distinguished by their ability to continually divide.

In two studies published today in Nature, researchers analyzed the genome of induced pluripotent stem (iPS) cells, adult cells that have been genetically or chemically reverted to the pluripotent, embryonic-like stem cell state. These cells have attracted intense interest from both scientists and the public as a potential alternative to embryonic stem cells. Similar to embryonic stem cells, iPS cells can differentiate into any type of tissue, rendering them good candidates for cell-replacement therapies. They are also genetically matched to the patient, meaning they don't carry the risk of immune rejection associated with some existing cell transplants.

Some of the mutations may arise from the evolutionary pressure of growing the iPSCs in a dish. If a random mutation occurs during cell division helps daughter cells grow faster than others, that mutation will propagate in the population. However, Zhang's team found that the mutation rate in iPSCs was 10 times the typical rate for cultured cells. Thus the mutations seem to be endemic to the iPSC themselves and not as a result of the culture process. These studies, once again, show that iPSCs are not yet a substitute for embryonic stem cells.

Wednesday, March 2, 2011

Fructose Promotes Pancreatic Cancer Growth Through Induction Of Transketolase Flux

A group of professors at UCLA, including a former colleague of mine, Dr. Laszlo Boros, report their work demonstrating that carbohydrate metabolism via glycolysis and the tricarboxylic acid cycle is pivotal for cancer growth, and increased refined carbohydrate consumption adversely affects cancer survival. As the authors state, traditionally, glucose and fructose have been considered as interchangeable sugars that are similarly metabolized, and most studies have focused on one sugar, namely glucose. 

However, fructose intake has increased dramatically in recent decades, especially as sourced from corn to make high-fructose corn syrup. Cellular uptake of glucose and fructose uses distinct transporters, or different methods for incorporation into cells. In the study spearheaded by lead author, Professor Anthony Heany, the authors report that fructose provides an alternative energy source to induce pancreatic cancer cell proliferation. 

Importantly, the authors show that fructose and glucose metabolism are very different; in comparison with glucose, fructose induces thiamine-dependent transketolase flux and is preferentially metabolized via the nonoxidative pentose phosphate pathway to synthesize nucleic acids and increase uric acid production.

These findings show that cancer cells can readily metabolize fructose to increase proliferation. The data suggest that cancer patients reduce dietary refined fructose consumption, and indicate that efforts to reduce refined fructose intake or inhibit fructose-mediated actions may disrupt cancer growth. Cancer Res; 70(15); 6368–76. ©2010 AACR.