Stem Cell Stories that Caught our Eye: CRISPRing Human Embryos, brain stem cells slow aging & BrainStorm ALS trial joins CIRM Alpha Clinics

Here are the stem cell stories that caught our eye this week. Enjoy!

Scientists claim first CRISPR editing of human embryos in the US.

Here’s the big story this week. Scientists from Portland, Oregon claim they genetically modified human embryos using the CRISPR/Cas9 gene editing technology. While their results have yet to be published in a peer review journal (though the team say they are going to be published in a prominent journal next month), if they prove true, the study will be the first successful attempt to modify human embryos in the US.

A representation of an embryo being fertilized. Scientists can inject CRISPR during fertilization to correct genetic disorders. (Getty Images).

Steve Connor from MIT Technology Review broke the story earlier this week noting that the only reports of human embryo modification were published by Chinese scientists. The China studies revealed troubling findings. CRISPR caused “off-target” effects, a situation where the CRISPR machinery randomly introduces genetic errors in a cell’s DNA, in the embryos. It also caused mosaicism, a condition where the desired DNA sequences aren’t genetically corrected in all the cells of an embryo producing an individual with cells that have different genomes. Putting aside the ethical conundrum of modifying human embryos, these studies suggested that current gene editing technologies weren’t accurate enough to safely modify human embryos.

But a new chapter in human embryo modification is beginning. Shoukhrat Mitalipov (who is a member of CIRM’s Grants Working Group, the panel of scientific experts that reviews our funding applications) and his team from the Oregon Health and Science University said that they have developed a method to successfully modify donated human embryos that avoids the problems experienced by the Chinese scientists. The team found that introducing CRISPR at the same time an embryo was being fertilized led to successful correction of disease-causing mutations while avoiding mosaicism and “off-target” effects. They grew these embryos for a few days to confirm that the genetic modifications had worked before destroying them.

The MIT piece quoted a scientist who knows of Mitalipov’s work,

“It is proof of principle that it can work. They significantly reduced mosaicism. I don’t think it’s the start of clinical trials yet, but it does take it further than anyone has before.”

Does this discovery, if it’s true, open the door further for the creation of designer babies? For discussions about the future scientific and ethical implications of this research, I recommend reading Paul Knoepfler’s blog, this piece by Megan Molteni in Wired Magazine and Jessica Berg’s article in The Conversation.

Brain stem cells slow aging in mice

The quest for eternal youth might be one step closer thanks to a new study published this week in the journal Nature. Scientists from the Albert Einstein College of Medicine in New York discovered that stem cells found in an area of the brain called the hypothalamus can slow the aging process in mice.

The hypothalamus is located smack in the center of your brain near the brain stem. It’s responsible for essential metabolic functions such as making and secreting hormones, managing body temperature and controlling feelings of hunger and thirst. Because the body’s metabolic functions decline with age, scientists have suspected that the hypothalamus plays a role in aging.

The mouse hypothalamus. (NIH, Wikimedia).

In the current study, the team found that stem cells in the hypothalamus gradually disappear as mice age. They were curious whether the disappearance of these stem cells could jump start the aging process. When they removed these stem cells, the mice showed more advanced mental and physical signs of aging compared to untreated mice.

They also conducted the opposite experiment where they transplanted hypothalamic stem cells taken from baby mice (the idea being that these stem cells would exhibit more “youthful” qualities) into the brains of middle-aged mice and saw improvements in mental and physical functions and a 10% increase in lifespan.

So what is it about these specific stem cells that slows down aging? Do they replenish the aging brain with new healthy cells or do they secrete factors that keep the brain healthy? Interestingly, the scientists found that these stem cells secreted vesicles that contained microRNAs, which are molecules that regulate gene expression by turning genes on or off.

They injected these microRNAs into the brains of middle-aged mice and found that they reversed symptoms of aging including cognitive decline and muscle degeneration. Furthermore, when they removed hypothalamic stem cells from middle-aged mice and treated them with the microRNAs, they saw the same anti-aging effects.

In an interview with Nature News, senior author on the study, Dongsheng Cai, commented that hypothalamic stem cells could have multiple ways of regulating aging and that microRNAs are just one of their tools. For this research to translate into an anti-aging therapy, “Cai suspects that anti-ageing therapies targeting the hypothalamus would need to be administered in middle age, before a person’s muscles and metabolism have degenerated beyond a point that could be reversed.”

This study and its “Fountain of Youth” implications has received ample attention from the media. You can read more coverage from The Scientist, GenBio, and the original Albert Einstein press release.

BrainStorm ALS trial joins the CIRM Alpha Clinics

Last month, the CIRM Board approved $15.9 million in funding for BrainStorm Cell Therapeutic’s Phase 3 trial that’s testing a stem cell therapy to treat patients with a devastating neurodegenerative disease called amyotrophic lateral sclerosis or ALS (also known as Lou Gehrig’s disease).

The stem cell therapy, called NurOwn®, is made of mesenchymal stem cells extracted from a patient’s bone marrow. The stem cells are genetically modified to secrete neurotrophic factors that keep neurons in the brain healthy and prevent their destruction by diseases like ALS.

BrainStorm has tested NurOwn in early stage clinical trials in Israel and in a Phase 2 study in the US. These trials revealed that the treatment was “safe and well tolerated” and that “NurOwn also achieved multiple secondary efficacy endpoints, showing clear evidence of a clinically meaningful benefit.  Notably, response rates were higher for NurOwn-treated subjects compared to placebo at all time points in the study out to 24 weeks.”

This week, BrainStorm announced that it will launch its Phase 3 CIRM-funded trial at the UC Irvine (UCI) CIRM Alpha Stem Cell Clinic. The Alpha Clinics are a network of top medical centers in California that specialize in delivering high quality stem cell clinical trials to patients. UCI is one of four medical centers including UCLA, City of Hope, and UCSD, that make up three Alpha Clinics currently supporting 38 stem cell trials in the state.

Along with UCI, BrainStorm’s Phase 3 trial will also be conducted at two other sites in the US: Mass General Hospital in Boston and California Pacific Medical Center in San Francisco. Chaim Lebovits, President and CEO, commented,

“We are privileged to have UCI and Dr. Namita Goyal join our pivotal Phase 3 study of NurOwn. Adding UCI as an enrolling center with Dr. Goyal as Principal Investigator will make the treatment more accessible to patients in California, and we welcome the opportunity to work with this prestigious institution.”

Before the Phase 3 trial can launch at UCI, it needs to be approved by our federal regulatory agency, the Food and Drug Administration (FDA), and an Institutional Review Board (IRB), which is an independent ethics committee that reviews biomedical research on human subjects. Both these steps are required to ensure that a therapy is safe to test in patients.

With promising data from their Phase 1 and 2 trials, BrainStorm’s Phase 3 trial will likely get the green light to move forward. Dr. Goyal, who will lead the trial at the UCI Alpha Clinic, concluded:

“NurOwn is a very promising treatment with compelling Phase 2 data in patients with ALS; we look forward to further advancing it in clinical development and confirming the therapeutic benefit with Brainstorm.”

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