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"The method does not make any progress and will never be the basis for the therapy." With these words, the renowned magazine "Nature Medicine" in 2005 rejected the Don Cliveland manuscript. In the paper, the professor described it medicine and neuroscience at the University of California, San Diego A new way to treat degenerative diseases of amyotrophic nerve disease (ALS) – a disease experienced by world-famous physicist Stephen Havking until his death. Cleveland and his team could demonstrate in experiments with mice that the so-called designer DNA drug significantly slows down the course of the disease.

Today, 13 years later, the new therapy developed by Don Cleveland is on the verge of using patients. Several clinical trials are already under way with designer DNA drugs. And this is not only in the hereditary form of ALS, but in other neurodegenerative diseases such as Huntington's disease of the genetic disease, Alzheimer's or frontotemporal dementia.

The principle is always the same: designer DNA drugs, the so-called. Antisense oligonucleotides (ASOs) ensure that the production of the protein causing the disease is suppressed. In Alzheimer's or frontotemporal dementia, for example, this is a "tau" protein that can accumulate in the nerve cells and thereby lead to cell death.

The DNA for the form of muscle loss is on the market

In another nerve disease, spinal muscular atrophy (SMA), new DNA drugs have already arrived in patients. In this hereditary disease, the so-called motor neurons do not work properly, those are the nerve cells that affect the muscles of the spinal cord. The reason for this is a defective protein. As a result, muscles through the body degenerate due to the lack of stimulation by motor neurons.

Babies born with the most severe form of SMA can not sit, hold their head or turn, they also struggle to breathe and swallow; Usually they do not survive the second birthday. Last year, the first cure for a deadly hereditary disease was approved. Lek Spinraza (the manufacturer of Biogen), based on the principle developed by Cleveland, slows down some muscles massively massive, some of the treated children are developing almost normal.

ALS, a disease Steven Hoking suffered, could soon be treated. Photo: Getti

It takes several years to make sure that the success of new DNA drugs in ALS, Alzheimer's and other neurodegenerative diseases will be so great. They always give reason to hope. For example, in Huntington. The first clinical trial was so promising that the pharmaceutical company Roche in Basel bought the development and marketing rights for the therapy from biotechnology company California Ionis in April. By the end of 2018 or early 2019, Roche plans to launch a major clinical examination. "We know the drug is safe," Cleveland said, "and I hope the patients will benefit."

Looks like Cleveland's persistence is paying off. A few years ago, he was exhausted with the idea of ​​paralyzing pre-active or irregularly active genes with DNA fragments and in this way reducing protein production, he speaks to us at our meeting in preparation of the "Honorable scientists" award of the private Swiss organization Nomis October. In cell biology it was eventually recognized that textbooks were not working. "It seems, however, that the nerve cells did not read the textbooks," he added with a smile, and immediately testifies to the aforementioned anecdote by rejecting his manuscript "Natural Medicine".

In his dissertation, the protein «tau»

Cleveland is laughing at this very moment, because he and his team at the Louis Cancer Research Institute in San Diego have developed a method that will allow them to treat many other illnesses in the future-and that's what the list says Glioblast, an incurable tumor of the brain and today. For this breakthrough, Cleveland received a passing $ 3 million pass-win last year. Now the price of the Nomis Foundation. At the award ceremony, Cleveland was commended accordingly. "You will be the first scientist to bring therapies against destructive neurodegenerative diseases in the clinic," said Alhajmer researcher Christian Haass of the University of Munich.

Research has always been more than the profession of Don Cleveland. "I always wanted to become a scientist," he says. "I can not think of anything else." Cleveland grew up with two brothers and sisters in the state of New Mexico, not far from the Mexican border. His father taught physics at the local faculty, and one of his nurses still works in chemistry today. Cleveland first studied physics, but then moved on to biochemistry during his doctoral dissertation in Princeton. During this period, he made his first breakthrough: he isolated and described in 1977 the protein "tau", a protein that is formed in Alzheimer, but also in boxer and footballer cases "Chronic Traumatic Encephalopathy" (CTE) and Nerve Cells Destroyed From Within .

Later he managed to clarify the complicated mechanism of cell division, the fundamental process of biology.

His career was so well run. And he continued like that. He was also the first to isolate and describe protein gene known as keratin (hair), actin (muscle) or tubulin (cytoskeleton). Later he managed to clarify the complicated mechanism of cell division, the fundamental process of biology. And then only the development of designer DNA drugs against various neurodegenerative diseases.

The last idea of ​​the 68-year-old already continues: Cleveland wants to regenerate new nerve cells in the brain. Dementia diseases such as Alzheimer's disease, Parkinson's or even CTEs kill countless nerve cells. As a rule, there is still enough cell to support, so-called. Astrocytes, which, unlike nervous cells, easily regenerate. His team has now managed to use DNA drugs to convert astrocytes to nerve cells. And they would be surrounded properly by mice, says Cleveland. "I never expected it." Probably, it's also different in textbooks.

(Editors Tamedia)

Created: November 16, 2018, 19:16 hours

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