Severine Kirchner

Stem cell therapy and RNA interference (RNAi) may be the sexiest hook-up since peanut butter and chocolate. And scientists are just beginning to explore the potential of combining these medical therapies.

Until very recently, the application of each therapy seemed very specific and limited: stem cells for regenerative medicine; RNAi for genetic correction. Furthermore, the repairing abilities of stem cells seemed more limited than first expected, and RNAi proved very difficult to be delivered to its intended targets.

But researchers recently discovered that the weakness of one technique was the strength of the other. So some research teams began combining the two to develop innovative and effective therapeutic tools for victims of neurodegenerative disorders like Huntington’s disease (HD).

At present, no preventative or curative treatments exist for HD, a hereditary disorder in which nerve cells (neurons) progressively breakdown in certain parts of the brain. Victims of the disease experience uncontrolled movements, dementia and eventually die from complications (infection, heart failure and pneumonia) that arise from the effects of HD on the body.

Normal human DNA contains a gene that codes for Huntingtin protein (htt). But in HD victims, that particular gene mutates, leading to the production of abnormally long htt proteins. The elongated htt proteins degrade into smaller, toxic fragments that bind together and accumulate in neurons, disrupting their normal functions. [For the record, “huntingtin,” the protein, is spelled with an “i,” while “Huntington,” the disease, is spelled with an “o.”]

The degeneration and eventual death of neurons in certain areas of the brain underlie the signs and symptoms of HD. Therefore, reducing or eliminating the mutant htt would halt or slow the progression of the disease. Many researchers consider gene-silencing with RNAi the best candidate therapy for the job.

Here’s how it works: Scientists produce in vitro snippets of RNA, called small interfering RNA (siRNA). siRNA are a close relative of DNA that match a portion of the gene of interest — like, for example, the mutant gene that produces the abnormal htt protein. siRNA can destroy the gene’s products before they can be turned into a protein. So in theory, specialized siRNA could be designed to interfere with the mutated htt gene’s ability to produce the abnormal htt protein.

But the challenge remains how to dispatch the siRNA into the human brain in a sustained, safe and effective manner. And even after siRNA find its way to the brain, it still has to penetrate into the brain cells in order to reach the degenerating neurons’ of HD patients. This is where stem cells enter the picture. They might be able to help siRNA make this challenging journey.

A group led by Dr. Jan Nolta of the University of California Davis, has tested a unique and very ingenious method to pass siRNA into neurons using mesenchymal stem cells (MSC).

MSCs have a wide variety of important roles in the body, but what interests Nolta is their ability to converge on sites of injury — kind of like cellular paramedics. But unlike ordinary paramedics, MSCs would also be willing to perform a transplant on the spot, using their own organs to save their patient! MSCs fuse with the damaged cells and inject them directly with ‘spare parts’ to help aid healing.

Therefore, if the MSCs contained siRNA designed to reduce the amount of abnormal htt, MSCs could transport and deliver them right to the heart of the degenerating neurons and prevent htt accumulation.

Scientists can easily extract MSCs from fat or bone marrow of adult donors. In Dr. Nolta’s vision, MSCs, isolated from a patient, would be modified in vitro to carry and produce siRNA. These modified MSCs would then be injected back into the patient’s brain, or possibly blood. Because of their natural properties, MSCs would then sidle up to neurons, poke them with a membranous finger, and pump them full of the miracle therapy.

In a paper published this year in Molecular and Cellular Neuroscience, Nolta’s team documented that siRNA-carrying MSCs were able to reduce htt levels by 50% in the target cells…at least in a petri dish. The reduction was not complete, or permanent, but it served as a proof-of-principle that MSCs can indeed deliver siRNA to other cells.

Dr. Nolta’s team has ideas on how to optimize its MSCs/siRNA system and has started testing it in animal models.

“Not only is finding new treatments for Huntington’s disease a worthwhile pursuit on its own,” said Nolta, who recently received a prestigious Transformative Research Grant from the National Institutes of Health to pursue her research, “but the lessons we are learning are applicable to developing new therapies for other genetic disorders that involve excessive protein development and the need to reduce it. We have high hopes that these techniques may also be utilized in the fight against some forms of amyotrophic lateral sclerosis (Lou Gehrig’s disease) as well as Parkinson’s and other conditions.”

While a therapy based on Dr. Nolta’s approach remains far from the doctor’s office, stem cell treatments are closer than ever. Combining them with RNAi, the hottest technique in molecular biology, opens more possibilities and hopes than ever before of curing degenerative diseases.

Regards,

Severine Kirchner
for The Daily Reckoning

Severine Kirchner

After she obtained her PhD in nutrition and Food Science at the University of Bordeaux in 2004, Severine Kirchner left her native France to work as a molecular and cellular biologist in the United-States. Her successive appointments as a research associate for the University of Medicine and Dentistry of New Jersey and the University of California Irvine allowed her to conduct research on the metabolic disorders diabetes and obesity. For more than 10 years she has had a keen interest in new technologies such as transcriptomics and stem cell biology that she studied firsthand in the lab.

Recent Articles

Addison Wiggin
The Central Bank Experiment that’s Destroying the Economy

Addison Wiggin

When it comes to central bankers and the global economy, you might say the inmates are running the asylum. Today, Addison Wiggin sits down with Jim Rickards to discuss the ever-changing world of finance, the likelihood of hyperinflation hitting the U.S., and the massive economic experiment being conducted by the world's central bankers. Read on...


Laissez Faire
The Real Reason ISIS Wants You Dead

Chris Campbell

ISIS is a radical terrorist organization wreaking havoc across Northern Iraq. But its members come from all over the world - including many from Western Countries. The question no one's asking is why... Why are foreigners flocking to the Middle East to fight alongside ISIS? And how far does Obama really want to go? Chris Campbell explores...


How to Trade October Volatility

Greg Guenthner

When it comes to the stock market, October gets a bad rap. It's true, there have been some major crashes in October (ahem... Black Monday, Black Tuesday, etc.) but on a shorter timeline this month hasn't been nearly as bad as you might think. Today, Greg Guenthner offers an optimistic look at the month investors love to hate. Read on...


What the Reboot of the US Budget Means for Your Money

Byron King

Big government doesn't come cheap. And right now the U.S. government is one of the biggest in history. So far the budget writers have been able to move money around to keep the machine moving. But as Byron King points out, that will soon become much more difficult. Read on for the full story...


Invest Like a Shark in the “New” Stock Market

Wayne Mulligan

In the late '90s, financial TV personalities like Jim Cramer became mega stars - often drawing more ratings the ESPN. But that was over 15 years ago... That couldn't happen again, could it? Today, Wayne Mulligan details the new flock of personalities that are set to cash-in on a different kind of investment boom. Read on...