"The method does not provide any progress and will never become the basis for therapy." With these words, the renowned journal Nature Medicine in 2005 rejected the manuscript of Don Cleveland. In the article, the professor described medicine and Neurobiology at the University of California, San Diego. A new way to treat degenerative nerve disease. Side-by-side amy sclerosis (ALS) – the disease of the world-renowned physicist Stephen Hawking until his death. Cleveland and his team were able to show in experiments with mice that the so-called designer of the DNA drug significantly slows down the course of the disease.
Today, 13 years later, the new therapy developed by Don Cleveland is at the threshold of use in patients. Several clinical trials with DNA designers are under way. And not only in the inherited form of ALS, but also in other neurodegenerative diseases such as Huntington's genetic disease, Alzheimer's disease or premenstrual dementia.
The principle is always the same: designer DNA drugs, the so-called antisense oligonucleotides (ASO), ensure throttling of the production of the disease-causing protein. In the case of Alzheimer's dementia or frontotemporal dementia, this is, for example, a "tau" protein that can aggregate into bundles in nerve cells and thus lead to cell death.
A DNA medication in the form of muscle wasting is available on the market
In another nerve disease, spinal muscular atrophy (SMA), a new DNA drug has already reached patients. In this hereditary disease, so-called motor neurons do not work properly, they are nerve cells that drive the muscles of the spinal cord. The reason for this is a defective protein. As a result, the muscles of the whole body degenerate due to the lack of stimulation by motor neurons.
Children born with the most severe form of SMA can not sit, keep their heads or rotate, they also have difficulty breathing and swallowing; they usually do not experience their second birthday. Last year, the first drug was approved for a terminal hereditary disease. Spinraza (a producer of Biogen), which is based on the principle developed by Cleveland, slows down some of the massively massive muscles, some of the treated children developed almost normally.
ALS, the illness that Stephen Hawking suffered, may soon be curable. Photo: Getty
It takes several years to check whether the success of new DNA drugs in SLA, Alzheimer and other neurodegenerative diseases will be so great. They always give reason for hope. For example in Huntington. The first clinical trial was so promising that the Roche pharmaceutical company in Basel purchased in April the rights to develop and market as part of the Californian biotechnology company Ionis. By the end of 2018 Or at the beginning of 2019, Roche plans to start a serious clinical trial. "We know the medicine is safe," says Cleveland, "and I hope it will benefit patients."
Cleveland's stubbornness seems to pay off. A few years ago he was ridiculed by the idea of paralyzing overactive or improperly active genes with DNA fragments and thus reducing protein production, he tells us during our meeting in preparation for the "Distinguished Scientist Award" awarded by the private Swiss foundation Nomis Foundation in October. In cell biology textbooks, it was finally acknowledged that it did not work. "It seems, however, that nerve cells have not read the textbooks," he adds with a smile, and immediately mentions the anecdote mentioned earlier on the rejection of his manuscript by "Nature Medicine".
In his dissertation he isolated the "tau" protein
Cleveland was laughing now because he and his team at the Louis Institute for Cancer Research in San Diego developed a method that would allow them to heal many other diseases in the future – and so the Glioblastoma list, an incurable brain tumor to this day, says. In this turn, Cleveland received a $ 3 million breakthrough award last year. And now the price of the Nomis foundation. At the award ceremony, Cleveland was praised. "You will be the first scientist to bring therapies against destructive neurodegenerative diseases in the clinic," said Alzheimer's researcher Christian Haass of the University of Munich in speech.
Research has always been more than just a profession for Don Cleveland. "I've always wanted to become a scientist," he says. "I do not remember anything else." Cleveland grew up with two siblings in New Mexico, near the Mexican border. His father taught physics at a local college, and one of his sisters does the same in today's chemistry. Cleveland first studied physics, but then he went to biochemistry during his doctoral thesis at Princeton. At that time he made the first breakthrough: he isolated and described in 1977 protein "tau", a protein that arises in Alzheimer's disease, but also in boxing and football disease "Chronicle of chronic traumatic encephalopathy" (CTE) and Nerve cells destroyed from the inside.
Later, he was able to explain the complicated mechanism of cell division, the basic process of biology.
His career was so well started. And he continued at a similar pace. He was also the first to isolate and describe the genes of proteins known as keratin (hair), actin (muscle) or tubulin (cytoskeleton). Later, he was able to explain the complicated mechanism of cell division, the basic process of biology. And then only developing designers of DNA drugs against various neurodegenerative diseases.
The latest 68-year-old idea is already underway: Cleveland wants to revive new nerve cells in the brain. Dementia diseases, such as Alzheimer's, Parkinson's and even CTE, kill innumerable nerve cells. As a rule, it still has enough auxiliary cells, so-called astrocytes, which, unlike nerve cells, grow back easily. His team has now been able to use the DNA drug to convert the astrocytes into nerve cells. And they would have a good relationship with mice, says Cleveland. "I never expected it." I suppose it's different in textbooks.
Created: November 16, 2018, 19:16 clock