By Don C. Reed
Imagine a calm persuasive voice, telling you to pick up a gun, put it to your head, and squeeze the trigger—you would say no, of course– but what if that voice repeated itself, over and over, and it came from inside your mind?
Schizophrenia “afflicts an estimated 3 million Americans (with) hallucinatory symptoms, such as hearing voices… lifelong drug treatment…can help keep symptoms in check, but there is no cure—and ten per cent still surrender to the disease by taking their own lives.”
—Todd Dubnicoff, CIRM, May 8th, 2015
What might it be like to live with schizophrenia? Check out this three-minute video, courtesy of Rob Klein:
But what a difficult and complicated problem!
It seems like fumbling for car keys in the dark. The electricity has gone out, and you are calling to your spouse—“did you check on top of the refrigerator?” “No, nothing there, what about the drawer by the bed?”
But the challenge must be met. Several top scientists and their labs are struggling to understand and fight schizophrenia: here is my non-scientist’s interpretation of three pieces of the puzzle, work from Marius Wernig, Christina Chatzi, and Fred Gage, who are using different stem cell-based approaches to target the disease.
What causes schizophrenia? Could it be one of those genes that activate the parts of our body during development? Or maybe the opposite, de-activating rival genes– so one can be the strongest?
In nature, the cuckoo bird approaches a robin’s next, and puts its own egg among the others. When the cuckoo chick hatches, it is much bigger than the others, and eats more than its share—and the other chicks may actually starve.
Similarly, genes responsible for nerve development get the signals to become activated—while other genes get repressed and remain silent.
Marius Wernig, MD, associate professor of pathology at the Stanford University School of Medicine, points to a protein called Myt1l (mighty-one L), which “block(s) the activation of …genes.. related to lung, cartilage, heart and other(s). The one set of genes that Myt1L repressor did not act on was neuron-specific genes.” By turning off the genes for the other cell types, Myt1l pushes development of the nerve cells.
However, Wernig says, if there are problems (mutations) with Myt1L: “…neural (nerve) cells get a little confused.”
all-news/2017/04/nerve-cells- actively-repress-alternative- cell-fates.html
Such “confusion” may be devastating.
“Myt1L mutations have been recently found in people with autism, schizophrenia, major depression, and low I.Q….”
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While working at Sanford-Burnham, Christina Chatzi questioned: if one kind of neuron causes a mental illness, could a second kind of neuron inhibit the first? And if so, how do we provide the needed neurons?
Knowing that “some inhibitory neurons rely on…retinoic acid (a form of vitamin A)… Chatzi wondered if exposing embryonic stem cells to retinoic acid would result in these inhibitory neurons.”
Working with Gregg Duester in his lab, Chatzi found that mice who were not able to make the needed retinoic acid in their bodies had “a serious deficiency in (certain) neurons… (this has) been associated with several neurological disorders, including Huntington’s disease, autism, schizophrenia, and epilepsy.…”
But what if there was a way to study—not the nerve cells themselves—but the connections between them?
At the world-famous Salk Institute, named for Jonas Salk, the man who defeated polio, researchers are studying the communication between neurons by developing “mini-brain” brain models in a dish, where conditions can be controlled.
“In a lot of psychiatric diseases, there’s evidence of dysfunction in the connections between the cells,” says Professor and senior author Rusty Gage. “But it’s been very difficult to study the functional connections between human neurons in the lab, until now.”
Dr. Gage’s group has come up with a disease-in-a-dish model of schizophrenia: a way to study the condition without bothering a patient– by coaxing patient cells to grow into partial brain models. Using this methodology, the team compared the interactions of cells from people who had schizophrenia and those who did not.
One key difference they found? Neurons “in the schizophrenic group had dampened activity patterns and less signaling between the sets of neurons.”
Summarizing the three approaches, Mitra J. Hooshman, PhD, (Director of Scientific Programs for Americans for Cures Foundation) said:
“Dr. Wernig is using cell reprogramming techniques to identify the genes involved in development of schizophrenia… Dr. Chatzi is using embryonic stem cells to generate inhibitory neurons and study their role in the manifestation of (the disease)…and Dr. Gage is using the “disease in a dish” model to understand the role of neural networks in the development of schizophrenia.”
What do these three attack plans have in common?
They were all funded by the California Institute for Regenerative Medicine (CIRM), the state stem cell program that is fighting for treatments and cures.
CIRM fights for cure.
Until we have cure, we must have care: to support those who suffer mental illness. Let’s meet an expert in that area.
Alfred “AL” Rowlett serves on the board of directors of the California stem cell research program, as the patient advocate representative for mental illness. He was appointed there because of his life-long work for such non-profits as the Turning Point Community Programs (TPCP), for which he is Chief Executive Officer.
Al helps arrange service for children and adults with psychiatric disabilities– throughout their entire life span– in 8 northern California counties.
Working with psychiatrists, case managers and therapists, Al works to provide life skills training, housing benefits, and other forms of psychiatric rehabilitation and crisis support.—so the people in need can avoid being hospitalized.
“If they cannot come to our office, we go to them, sometimes twice a day, every day, sometimes for medication support. If they desire to work, can we help them find a job– and figure out how to get there every work day?
“There are obstacles and barriers such as trying to locate affordable housing. Social stigma is pervasive, all too often based on false images promoted in movies and on TV. Verifiable data suggests the opposite; individuals diagnosed with psychiatric illnesses are often ostracized and homeless. Often co-occurring symptoms associated with alcohol and drug use/abuse make for a deleterious outcome.”
Rowlett points to mental illnesses such as schizophrenia as having “clear evidence of a biological component”, meaning it may, in time, be overcome, or cured.
We need, in short, a funding program like the California Institute for Regenerative Medicine; we need CIRM. As Al puts it:
“CIRM is a place providing hope: where specific clinical interventions are sought—which may change the trajectory of a person’s life.”
Don C. Reed is the author of “CALIFORNIA CURES: How the California Stem Cell Program is Fighting Your Incurable Disease!”, from World Scientific Publishers, Inc., who brought you the work of the late Professor Stephen Hawking.