"The method does not provide any progress, and will never be the basis for treatment." In these words, the renowned journal Nature Medicine in 2005 rejected a manuscript by Don Cleveland. In the paper, the professor described medicine And Neuroscience at the University of California San Diego A New Way to Treat Neurodegenerative Amyotrophic Lateral Sclerosis (ALS) – The disease was suffered by world famous physicist Stephen Hawking until his death. Cleveland and his team were able to show experiments with mice that the so-called DNA designer drug significantly slows down the course of the disease.
Today, 13 years later, the innovative treatment developed by Don Cleveland is on the verge of using patients. Several clinical trials have been underway with DNA drugs. And it's not just an inherited form of ALS, but also other neurodegenerative diseases such as Huntington's genetic disease, Alzheimer's disease, or prefrontal dementia.
The principle is always the same: the molded DNA drugs, so-called oligonucleotides, can ensure that the production of a disease-causing protein is swallowed up. In dementia of Alzheimer's or Frontotemporal, for example, it is a "tau" protein, which can accumulate into bundles in nerve cells and thus lead to cell death.
DNA drug in the form of muscle wasting is on the market
In other neurodegenerative diseases, spinal muscular dystrophy (SMA), the new medicine of DNA has already reached patients.In this hereditary disease, motor neurons supposedly do not work properly, these are the nerve cells that drive the muscles from the spinal cord, Muscles throughout the body degenerate due to lack of stimulation by motor neurons.
Babies born with the heaviest form of SMA can not sit, hold their heads or turn around, they also struggle to breathe and swallow; They usually do not survive their second birthday. Last year, the first drug was approved for a fatal hereditary disease. The drug Spinraza (BioGen), based on the principle developed by Cleveland, slows down some of the massive muscles, some of the children and patients have evolved almost normally.
ALS, the disease that Stephen Hawking suffered from, may become treatment. Photo: Getty
It will take several years to see if the success of the new DNA drugs ALS, Alzheimer's and degenerative degenerative diseases will be so resonant. They always give reason to hope. For example, in Huntington. The first clinical trial was so promising that Roche Pharmaceuticals in Basel acquired the development and marketing rights for the treatment from Unis Biotech in June. At the end of 2018 or early 2019, Roche plans to launch a large clinical trial. "We know the drug is safe," says Cleveland, "and I hope it will benefit the patients."
The Cleveland principle seems to be paying off. A few years ago, it is ridiculed by the idea of overactively active or inactive gene paralysis with DNA fragments and thus reducing protein production, he tells us at our meeting ahead of the "Unique Scientist" award by the Swiss Private Nomis Foundation in October. In cell biology textbooks finally admitted it does not work. "However, it seems that the nerve cells did not read the textbooks," he adds with a smile, and immediately recounts the anecdote mentioned earlier in the rejection of his manuscript by "natural medicine."
In his work he isolated the protein "Tao"
Cleveland is laughing at the moment, as he and his team at the San Diego Cancer Institute have developed a method that will allow them to treat many other diseases in the future – and this is what Glioblastoma says, an incurable brain tumor to this day. For this breakthrough, Cleveland received the breakthrough award of $ 3 million last year. And now the price of the Nomis Fund. At the awards ceremony Cleveland was acclaimed accordingly. "You will be the first scientist to introduce treatments for devastating neurodegenerative diseases in the clinic," said Alzheimer's researcher Christian Haas of Munich University in the eulogy.
Research has always been more than a Don Cleveland profession. "I always wanted to be a scientist," he says. "I do not remember anything else." Cleveland grew up with two brothers in the state of New Mexico, not far from the Mexican border. His father taught physics at a local college, and one of his sisters still does so in chemistry. Cleveland studied physics first, but moved to biochemistry during his doctoral thesis at Princeton. During this period he made his first breakthrough: He isolated and described the protein "tau," the protein that makes up Alzheimer's, but also in boxer disease and "traumatic football".
Later, he was able to clarify the complex mechanism of cell division, the basic process of biology.
His career was launched so well. And it continued at a similar pace. He was also the first to isolate and describe genes in proteins known as keratin (hair), actin (muscle) or tubulin (cytoskeleton). Later, he was able to clarify the complex mechanism of cell division, the basic process of biology. Then only the development of designer DNA drugs against a variety of neurodegenerative diseases.
The 68-year-old's latest idea is already happening: Cleveland wants to grow new nerve cells in the brain. Dementia diseases like Alzheimer's, Parkinson's or even CTE kill innumerable neuronal cells. As a rule, it still has enough support cells, the so-called astrocytes, which, unlike nerve cells, regrow easily. His team has now been able to use a DNA drug to turn astrocytes into nerve cells, and they would merge with mice, says Cleveland, "I never expected that." This is probably different in the textbooks.
Created: 16.11.2018, 19:16 clock