"This method does not provide progress and will never form the basis for therapy." With these words, the famous journal "Nature Medicine" in 2005 rejected a text by Don Cleveland. In the newspaper, the professor was explained to drug and Neuroscience at the University of California in San Diego New Ways to Treat Degenerative Nerve Disease Amyotrophic Lateral Sclerosis (ALS) – a disease suffered by world-renowned physicist Stephen Hawking until his death. Cleveland and his team were able to demonstrate in experiments with mice that so-called designer DNA drugs significantly slowed the course of the disease.
Today, 13 years later, new therapies developed by Don Cleveland are on the threshold of use in patients. Several clinical trials have been carried out with designer DNA drugs. And this is not only in the hereditary form of ALS, but also in other neurodegenerative diseases such as Huntington's genetic disease, Alzheimer's or frontotemporal dementia.
The principle is always the same: The designer DNA drug, called antisense oligonucleotide (ASO), ensures that protein production causes disease to decrease. In Alzheimer's or frontotemporal dementia, for example, this is a "tau" protein, which can be combined into bundles in nerve cells and thus cause cell death.
DNA drugs for wasting muscle are on the market
In other neurological diseases, spinal muscular atrophy (SMA), new DNA drugs have arrived in the patient. In this hereditary disease, what are called motor neurons are not functioning properly, these are nerve cells that push the muscles of the spinal cord. The reason for this is the wrong protein. As a result, the muscles in the whole body degenerate due to lack of stimulation by motor neurons.
Babies born with the heaviest form of high school cannot sit, hold their heads or spin, they also struggle to breathe and swallow; usually they don't have a second birthday. Last year, the first drug was approved for deadly hereditary diseases. The Spinraza drug (manufacturer of Biogen), which is based on the principle developed by Cleveland, slowed down a number of muscles on a large scale, some children who were treated developed almost normally.
ALS, Stephen Hawking's disease, can be treated immediately. Photo: Getty
It will take several years to see whether the success of new DNA drugs in ALS, Alzheimer's, and other neurodegenerative diseases will be very echoing. They always give reasons for hope. For example, in Huntington. The first clinical trial was very promising that Roche pharmaceutical company in Basel bought development and marketing rights for therapy from California biotech company Ionis in April. At the end of 2018 or early 2019, Roche plans to launch a large clinical trial. "We know the drug is safe," Cleveland said, "and I hope this will benefit patients."
Cleveland's persistence seemed to pay off. A few years ago, he was ridiculed by the idea of crippling overactive or inactive genes with pieces of DNA and thereby reducing protein production, he told us at our meeting run-up to the "Distinguished Scientist Award" by the Nomis Swiss Private Foundation. October. In cell biology books it was finally recognized as unsuccessful. "It seems, however, that nerve cells have not read the textbook," he added with a smile, and immediately told the anecdote mentioned earlier with the rejection of the text by "Natural Medicine."
In his dissertation isolating protein «know»
Cleveland is enjoying laughter now, because he and his team at the San Diego Cancer Research Institute in San Diego have developed a method that will enable them to treat many other diseases in the future – and that is what the Glioblastoma list, a brain tumor that cannot be cured to today. For this breakthrough, Cleveland received a $ 3 million Breakthrough Prize last year. And now the price of the Nomis Foundation. At the award ceremony, Cleveland was praised as it should be. "You will be the first scientist to bring therapy against destructive neurodegenerative diseases in the clinic," Alzheimer's researcher Christian Haass from Munich University said in the speech.
Research is always more than a profession for Don Cleveland. "I always wanted to be a scientist," he said, "I can't remember anything else." Cleveland grew up with two siblings 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 did the same thing in chemistry today. Cleveland first studied physics, but later turned to biochemistry during his PhD thesis at Princeton. During this time, he made his first breakthrough: He isolated and explained in 1977 the "tau" protein, a protein formed in Alzheimer's, but also in Footballer boxers and diseases "Chronic Traumatic Encephalopathy" (CTE) balls and destroyed nerve cells from within.
Then, he succeeded in explaining the complex mechanism of cell division, the fundamental process of biology.
His career was very well launched. And it continues at the same speed. He was also the first to isolate and describe genes for proteins known as keratin (hair), actin (muscle) or tubulin (cytoskeleton). Then, he succeeded in explaining the complex mechanism of cell division, the fundamental process of biology. And then only the development of designer DNA drugs against various neurodegenerative diseases.
The latest idea of 68 years has gone on: Cleveland wants to grow new nerve cells in the brain. Dementia like Alzheimer's, Parkinson's or even CTE kills countless nerve cells. As a rule, he still has enough support cells, called astrocytes, which, in contrast to nerve cells, grow back easily. His team has now succeeded in using DNA drugs to make astrocytes turn into nerve cells. And they will be well connected with mice, said Cleveland. "I never expected that." Presumably, it is also different in the textbook.
Created: 16.11.2018, at 19:16