Stem cells and all Neurodegenerative diseases

Knowing that stem cells can differentiate into multiple cell types or all cells of the body (depending on their origin), transplantation of stem cells into an adult brain has been proposed as a future therapy for neurodegenerative diseases.
In each type of neurodegenerative disease (Hunnington’s disease, Alzheimer’s disease, Parkinson’s disease, ALS), there are many different cell types involved in their pathology, thus, different types of neurons are required for replacement.
This article http://celleng.sjtu.edu.cn/pic/xq19.pdf analyzes many neurodegenerative diseases and their potential for stem cell therapy. They show the challenges in the way for stem cell therapy, for we need to know how to pattern stem cells to obtain a more complete repertoire of various cell types for replacement. How are stem-cell-derived neurons integrated into an adult brain’s existing neural and synaptic network? How can we modify stem cells appropriately to treat a particular disease?
To identify the self-repair mechanisms of the brain, we’ll require a new technology for genetically labeling stem cell progeny. The hope is this knowledge will allow us to figure out a strategy to deliver new molecules that can yield functional neurons/cells in damaged areas.

Converting RBC Blood Groups by Cleaving Terminal Sugars

It struck me in class today that, with an enzyme to cleave either the A or B sugar from the end of the blood group glycolipid, you could create a 'O' erythrocytes from A, B, or AB individuals, expanding our supply of 'universal donor' blood while drastically reducing the risk of accidental mismatch.

As it turns out, I was not the first to have this idea - way back in 1983, it was demonstrated that a galactosidase derived from coffee beans is able to convert B RBCs into O, and that these cells are viable in people of any blood type (excluding the Bombay phenotype). Unfortunately, this method, and many others attempted for both A and B sugars, required a prohibitively large amount of enzyme and incompatable conditions, preventing its practical large scale use.

Recently (2007), researchers, doing a large scale scan of bacterial and fungal isolates, isolated two novel galactosidases which remove the A and B sugars much more efficently, and with identical, neutral pH, reaction conditions - allowing for the conversion of AB eyrithrocytes as well as A and B. Standard typing showed full conversion of any of the groups to O.

With a quick search, I wasn't able to find any more information on more progess towards making this a reality in blood banks, but hopefully someone's working on it...

References:

Liu Q, Sulzenbacher G, Yuan H, Bennett E, Pietz G, Saunders K, Spence J, Nudelman E, Levery S, White T, Neveu J, Lane W, Bourne Y, Olsson M, Henrissat B, Clausen H (2007). "Bacterial glycosidases for the production of universal red blood cells". Nat Biotechnol 25 (4): 454

Group B erythrocytes enzymically converted to group O survive normally in A, B, and O individuals. Goldstein, Jack; Siviglia, Geraldine; Hurst, Rosa; Lenny, Leslie; Reich, Lilian, Science (1982), 215(4529).

Sea anemone toxin may provide relief for MS patients.

Having read, A randomized crossover study of bee sting therapy for multiple sclerosis by Wesselius & Heersema et al., I was interested in other possible applications of animal venom in treatments similar to the apitherapy frequently used as an alternative care source for MS patients. In my inquiry I found an article on a sea anenome toxin that may act beneficially in the relapse of MS patients.

By Norton, Pennington and Wulff, Potassium Channel Blockade by the Sea Anemone Toxin ShK for the Treatment of Multiple Sclerosis, provides an overview of interaction between the toxin and potassium channels, the role of potassium cell in T-cells and the changes in potassium expression during T-cell differentiation.

Norton et al., site studies which state provide evidence showing that ShK has been able to prevent and treat adopted experimental autoimmune encephalymyelitis (EAE) in rodent models. ShK subcutaneously injected prevented EAE in a study in which all control animals died. ShK was even proven to ameliorate symptoms when treatment with ShK was delivered until after the presentation of the first symptom.

Ultimately, this paper provides just another example of possible solutions to human diseases that may be lie latent and undiscovered in other species. I always try and look at the human body holistically when discussing diseases, thinking of how all the systems interact; however, I think this articles reassures the discussion about preserving as many endangered species as possible, as we may not truly understand the potential that those animals hold.

Reference for the article: http://web.ebscohost.com/ehost/pdf?vid=2&hid=8&sid=8f2a0a67-151f-49cc-8910-280672d21490%40sessionmgr13

Iron Accumulation in the Brain may lead to AD and PD.

Multiple recent studies have been published pertaining to iron accumulation in the brain and a correlating incidence of neurological disorders. Many studies have been published particularly surrounding Alzheimer's and Parkinson's disease. Authored by Zecca et al., Iron, Brain Ageing and Neurodegenerative Disorders, focuses on this correlation.

Iron accumulation has been linked to multiple neurodegenerative diseases; it is believed that the build up iron causes an increased amount of oxidative stress which can be responsible for neurodegeneration. The iron accumulation in the brain increases preferentially in areas that are impacted by AD and PD. Some evidence seems to indicate that the accumulation of iron in the microglia induces the inflammatory response common amongst many neurodegenerative diseases.

In the case of Parkinson's Disease, increased iron accumulation is seen in the substantia nigra in extreme cases. Iron (III) specifically can be seen accumulated in the oligodendrocytes, astrocytes, microglia and portions of the substantia nigra of PD patients. In Alzheimer's Disease, iron seems to promote both deposition of amyloid-B and oxidative stress which are associated with plaque deposition.

This provides a unique link between metabolic needs, nutritional regulation and neurodegenerative diseases.

Reference for the article: http://www.nature.com/nrn/journal/v5/n11/pdf/nrn1537.pdf

New Clues to How Fish Oils Help Arthritis Patients

I've always heard that fish oils are good at reducing inflammation. I thought this article was interesting I tried finding a more specific and in depth summary of how Resolvin D2 promoted edothlial cells to produce NO to prevent the macrophages from attacking the cells. I'd like to hear other opinions on the subject. I's sure we can all agree nutrition is very important for arthritis patients. maybe we can find a more detailed summary of the pathway.

Findings may boost treatments for other inflammatory diseases, researchers say

Posted October 28, 2009

WEDNESDAY, Oct. 28 (HealthDay News) -- Researchers think they now understand the way that fish oils benefit people with rheumatoid arthritis and other conditions linked to inflammation.

The body converts an ingredient in fish oils called DHA into a chemical called Resolvin D2, which reduces the inflammation that can lead to various diseases, the scientists from Queen Mary, University of London and Harvard Medical School explained in their study published in the Oct. 28 issue of the journal Nature.

"We have known for some time that fish oils can help with conditions like arthritis, which are linked to inflammation. What we've shown here is how the body processes a particular ingredient of fish oils into Resolvin D2. We've also looked in detail at this chemical, determining at least some of the ways it relieves inflammation. It seems to be a very powerful chemical and a small amount can have a large effect," Mauro Perretti, a professor of immunopharmacology at Queen Mary, University of London, said in a university news release.

"This research is important because it explains at least one way in which fish oils can help in different types of arthritis. We can also work on this chemical and see if it can be used not only to treat or even prevent arthritis, but also as a possible treatment for a variety of other diseases associated with inflammation," said Perretti, who led the U.K. research team.

Unlike current anti-inflammatory drugs, Resolvin D2 doesn't appear to suppress the immune system, the researchers noted.

In arthritis, the body's immune system attacks healthy tissue. An important part of this process occurs when white blood cells (leukocytes) stick to the inner lining (endothelium) of blood vessels. In lab tests, Perretti and colleagues found that Resolvin D2 prompted endothelial cells to produce small amounts of nitric oxide, which acts as chemical signal that discourages white blood cells from sticking to the endothelium, thus preventing inflammation.

More information

The American Academy of Family Physicians has more about rheumatoid arthritis.

Link Between Pain Thresholds, Inflammation And Sleep Problems In Arthritis Patients

As a college student sleep is sometimes a luxury, I often find it difficult to find time to sleep with all the deadlines and daily activities. My concern for lack of sleep lead me to this lay article on RA and pain threshold for sleep disorders. I found it interesting and thought I'd share it with everyone. I thought it would be interesting to consider how sleep or more specifically sleep deprivation related to disease. can anyone think of any possible relationships between RA and sleep deprivation aside from increased stress and damage leading to increased inflammation?

Article Date: 29 Oct 2009 - 5:00 PDT

Despite recent advances in anti-inflammatory therapy, many rheumatoid arthritis (RA) patients continue to suffer from pain. Research published in BioMed Central's open access journal, Arthritis Research & Therapy found that inflammation is associated with heightened pain sensitivity at joint sites, whereas increased sleep problems are associated with heightened pain sensitivity at both joint and non-joint sites.

Researchers from the Division of Rheumatology and Pain Management Center of Brigham and Women's Hospital, and the Chronic Pain and Fatigue Center of the University of Michigan Medical School, assessed experimental pain sensitivity, disease activity, sleep problems and psychiatric distress in 59 women with RA. The researchers used questionnaires to assess the women's sleep problems and psychiatric distress and measured the levels of C-reactive protein as an indicator of disease activity. They also measured pain sensitivity with pressure pain threshold testing at joint and non-joint sites. Lower pain thresholds are indicative of higher pain sensitivity.

"Sleep problems were inversely associated with pain threshold at all sites, suggesting a defect in central pain processing", state the authors. This finding emphasises the need for research into the mechanisms underlying sleep disorders and pain in RA patients, particularly given the common occurrence of sleeping problems among these patients. This autoimmune disease, causing chronic inflammation, affects nearly 1% of the population and sufferers often report ongoing pain in spite of successful anti-inflammatory treatment.

"Since differences in pain sensitivity may shape the course of pain complaints and influence treatment decisions, it is important to understand the factors associated with enhanced pain sensitivity", lead author Yvonne Lee says, adding, "Physicians and researchers should consider both inflammatory and non-inflammatory factors when evaluating pain in research settings and in the clinic."

Notes:
The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study
Yvonne C Lee, Lori B Chibnik, Bing Lu, Ajay D Wasan, Robert R Edwards, Anne H Fossel, Simon M Helfgott, Daniel H Solomon, Daniel J Clauw and Elizabeth W Karlson
Arthritis Research & Therapy (in press)
http://arthritis-research.com/

Source:
Charlotte Webber
BioMed Central

Blood Brain Barrier Breakdown Precedes Infiltration in MS

As we discussed in class, Multiple Sclerosis is currently an idiopathic disorder with no known precipitating cause. Clinically it manifests itself as demyelinated areas of the central nervous system called lesions that contain blood derived immune monocytes. Because the immune system and the central nervous system are normally separated the immune cells are unable to discriminate between brain antigens and foreign antigens.
It is for this reason Multiple sclerosis has been considered an autoimmune disorder and therapies have centered around attempting to modify the inflammatory response and try to depress what seems to be considered an overactive immune system response. In the review article from last class by Martino and associates, it was noted that the blood brain barrier showed enhanced leakiness around the sites of the lesions but it was unknown whether this preceded or was a result of an already initiated immune response. I see this as a pivotal question to answer in the quest for a treatment of multiple sclerosis. Obviously at some point damage is done by the blood born immune system but is this behavior due to an aberrant immune response in need of correction or is it simply working perfectly against antigens that it should never have had the opportunity to encounter in the first place?
According to a paper by Floris and associates in the journal Brain, they were able to determine that in animal models with allergic encephalomyelitis (EAE) MRI imaging with gadolinium showed that vascular leakage and onset of neurological signs occurred concomitantly BEFORE the infiltration of immune monocytes. This suggests that cerebrovascular leakage and monocyte infiltration are two distinct events in the development of the lesions. This may be a very important consideration in the direction of research and the development of new therapies for multiple sclerosis.