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Edward R. Biehl, co-discoverer of the HSB-13 compound  (Source: vvoice.vo.llnwd.net)
HSB-13 compound could halt diseases like Alzheimer's, Huntington's and Parkinson's

Southern Methodist University (SMU) and University of Texas at Dallas researchers have found hope for those suffering from diseases like Alzheimer's, Parkinson's and Huntington's through the discovery of a group of molecules which could help protect the brain.

Edward R. Biehl, study leader and a synthetic organic chemist at SMU, and Santosh R. D'Mello, co-author of the study and a biology professor at UT Dallas, have developed the compounds in an effort to halt the onset of nerve-degenerative diseases and relieve symptoms. 

Alzheimer's, Parkinson's and and Huntington's are neurodegenerative diseases in the central nervous system, and afflict more than five million Americans (mainly senior citizens). These diseases are caused by the immoderate loss of neurons in an area of the mid-brain, which leads to a decline in motor skills, such as walking and speaking, as well as memory loss and behavior problems. 

Previous treatments cannot halt or reverse these types of nerve-degenerative diseases. They only relieve symptoms, and sometimes even fail at that due to the severe side effects of these medications. 

But now, Biehl and D'Mello have worked together to develop compounds that could potentially protect the brain from nerve-degenerative diseases. They came upon this discovery when developing synthetic chemicals that contained a class of heterocyclic organic compounds. One particular compound in the heterocyclic class proved to be protective of neurons in tissue culture models. Furthermore, this same compound, named HSB-13, has also proven to be effective in fighting neurodegenerative diseases in animal models. 

"Our compounds protect against neurodegeneration in mice," said Biehl. "Given successful development of the compounds into drug therapies, they would serve as an effective treatment for patients with degenerative brain diseases."

HSB-13 not only decreased degeneration in the forebrain, but also corrected behavioral problems. It has also proved to be nontoxic while remaining "extremely potent."

Biotechnology and therapeutics company EncephRx, which is based in Dallas, is looking to create drug therapies based on this new class of compounds. The company was granted worldwide license to the "jointly owned compounds," and when the research is complete, EncephRx's pharmaceuticals made of these small compounds will be the first therapeutic tools capable of protecting brain cells and keeping them from dying. 

"Additional research needs to be done, but these compounds have the potential for stopping or slowing the relentless loss of brain cells in diseases such as Alzheimer's and Parkinson's," said D'Mello. "The protective effect that they display in tissue culture and animal models of neurodegenerative disease provides strong evidence of their promise as drugs to treat neurodegenerative disorders."



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I'm curious about a few things...
By MrBlastman on 12/8/2010 11:55:52 AM , Rating: 3
This compound specifically blocks the neurodegenerative effects of these three diseases--the mechanism through which they operate is in ways similar. Prions, or abnormal proteins directly affect the neural structures causing scattered cellular death. Of course, the areas affected are similar but different in each of the conditions. The linking factor is the abnormal protein.

What it seems to me is that this compound somehow blocks the protein from accumulating. There are two ways I think this might occur and the article does not specify:

a. Binding itself to these sinister proteins in such a way that they are then able to be attacked and elminated by the immune system or, better yet, ejected from the body through either the liver or the kidneys. From what I have read on CJD (mad cow), only a few prions are neccessary to start the process and, through cellular invasion, they spawn additional prions and through an exponential factor, they eventually reach the saturation neccessary to cause noticeable effects. If you eliminate these proteins from the body, you slow the process and eventually stop it.

b. Binding itself directly to the neurons via their axons, dendrites, soma (specifically the soma) creating an additional "sheath" thus preventing contact with the prion much like flypaper stops a fly or plexiglass stops a thug from breaking into a store.

I'm curious as to which of the two mechanisms it uses to achieve this goal. My worry with b. would be the accumulation of the compound over time in the human brain which in turn could prevent additional synapses and neural-interconnects from being formed thus creating a more "rigid" brain.

The other thing I'm curious about goes back to a. and that is CJD or Mad Cow disease. If this compound is successful in attacking these proteins, would it also be beneficial to those suffering from these other diseases. Furthermore, I wonder if it could be used as a preventative agent--i.e. inject beef with it to reduce the potential instances of it as a safety measure (though, this would really only be useful if mechanism a. were the pathway and not b.).

This is a really amazing find and I applaud these researchers in their work.




RE: I'm curious about a few things...
By RugMuch on 12/8/2010 12:38:56 PM , Rating: 2
b. your saying that the cell is like toppled forest and adds to the cell from the exterior in? not grows inside out and disintegrates from the outside in like skin?


RE: I'm curious about a few things...
By MrBlastman on 12/8/2010 1:10:19 PM , Rating: 2
Well, really, as I understand it, prions gain entry via the celluar wall into neurons and then through some process of division, they encourage the cell to generate new prions and via protein conversion within the cell. The cell then either vacuolizes or dies and releases the produced prions, which then set out to invade other cells.

So with b., what I'm wondering is if the compound forms an additional layer on the outside of the cell wall blocking the proteins before they gain entry through the cell membrane into the cell.

The only problem with b. is that it insinuates the compound sticks around over time.


By geddarkstorm on 12/8/2010 1:27:00 PM , Rating: 2
The prion state that causes disease is an alternate 3D conformation of the natural prion protein. It just so happens, a prion protein in this alternate state can then catalyze the conversion of a normal prion also into this state.

The converted prions then stack into a filament, and it's this filamentous bundle that eventually leads to cellular dysfunction and death. This is very similar to how the AB plagues work that contribute to Alzheimer's. How exactly the filaments damage cells is unknown, though inflammation is triggered and inflammation is highly damaging to cells caught in it (part of the point of inflammation).

What natural prions do, may be related to ion balance, but it is rather unknown. Still, they are likely not the culprits behind these three diseases; and actual prion disease (Mad Cow Disease), has a very different phenotype, both on cognitive degeneration and in the pattern of how the cells die.


By geddarkstorm on 12/8/2010 1:18:28 PM , Rating: 2
Well, this may have nothing to do with prions. In fact, most research suggests that it's the immune system that is responsible for the neural degeneration of these three diseases. Each triggers the inflammation response differently, but once it starts, and macrophages invade the brain, that's the point when neurons start to die and degeneration occurs. Many modulators of the immune system can completely block these diseases, they just also happen to be totally impractical and toxic in the long run.

Rampamycin is a nice example, even extends life span significantly... by turning off the immune system.

Now, what these compounds could be doing, is preventing the signaling of the immune invasion into the brain. There have been other compounds that can do this, and protect from neural degeneration, they just aren't very potent and have problems with the blood brain barrier. What is sounds like, is these new compounds have overcome those technicalities and may even be far more potent.

Now, this is just one hypothesis, and yours are just as valid. It'll be very interesting to find out how exactly these compounds are causing the protection. Might even be via stimulation of neurogenesis for all we know.


By jimhsu on 12/9/2010 8:34:47 AM , Rating: 2
Theoretically we can test all of these things:

a. Detect protein binding via a FRET-like system (google FRET), yeast two-hybrid, GST pulldown, etc. If the small molecule makes elimination easier, you could also track the protein itself via renal or bile secretions. You could of course radiolabel the small molecule and trace where it goes.

b. Again, radiolabel it to see where it goes. Track metabolism and elimination. Determine if inhibition of the hypothetical neuron-small molecule interaction disrupts the efficacy.

Am I just nerdy, or is he holding a reagant bottle from Fisher Scientific (probably a salt of some kind) and standing behind a GC-FID readout with a solvent peak (probably ethanol or acetone or something of that sort)?


Nootropics
By RivuxGamma on 12/8/2010 12:58:50 PM , Rating: 2
Yes, it's a term used in The Lawnmower Man, but they're real. Stuff similar to this already exists like piracetam and others like it.

They can even protect from severe brain damage by drugs or even electric shock. Granted, that's something hard to anticipate unless you're going to the electric chair soon, or something like that, but it's possible.




RE: Nootropics
By MrBlastman on 12/8/2010 1:18:23 PM , Rating: 2
Nootropics work through an entirely different mechanism than this compound potentially. Nootropics, while having been around for years, alter the neurochemical structure, stimulate nerve growth or provide cognitive enhancements.

This compound here does none of that--from what I read it stops the destructive mechanisms in their tracks.


RE: Nootropics
By geddarkstorm on 12/8/2010 1:33:15 PM , Rating: 2
Nootropics like piracetam are very fascinating. They are indeed a highly different mechanism, seemingly mediated by changing the membrane fluidity of neurons, and thus their action potential parameters (piracetam does not affect neural transmitter balance, which is a very important feature for safety and what distinguishes it from drugs). Somehow, this also upregulates neurogenesis, which is where the cognitive enhancements may stem (along with the better synchrony of ECG waves and hemisphere communication).

But yes, just like you say, they can't stop these diseases; they are meant for healthy individuals. They may lower the chance to acquire, but once it's there the nootropics can only slightly (maybe) decrease severity of symptoms but not alter the cause. That's what makes this new compound so exciting--and it'll likely not affect cognitive functions and IQ in healthy individuals.


HSB-13
By frozentundra123456 on 12/9/2010 12:00:23 AM , Rating: 3
Prions cause mad cow disease and a similar syndrome in humans called Crutzfield-Jacobs disease. They do not cause Alzheimer's or any other neurodegenerative diseases that I am aware of. Alzheimer's is characterized by a build up of plaques and neurofillibrary tangles. They are abnormal proteins, but are not prions.

I wish the article had given some indication of how this drug works. I worked in a research lab for several years studying Alzheimer's disease, and there are many drugs that somewhat slow down the progression of the disease, but many have not lived up to what their developers hoped for because of either bad side effects or less than expected efficacy of treatment.
Here is hoping that maybe there is a significant advance.




RE: HSB-13
By Lugaidster on 12/9/2010 10:01:43 AM , Rating: 2
According to these:
http://www.ncbi.nlm.nih.gov/pubmed/20143421

It inhibits three key enzymes that trigger cell death in these diseases, thus, stopping the progression. Probably won't cure it, meaning that the affected might need to live taking the compound. Maybe with another drug that triggers neurogenesis it could restore some functions to the brain.

I hope we see this available soon. There's nothing worse than to loose your cognitive skills IMO.


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