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A team led by the University of California, San Diego receives $ 9 million to advance Parkinson’s disease treatment




Researchers around the world have tried many methods, and for years, to generate neurons in the laboratory. On-demand neurons may also offer therapeutic options to replace neurons lost in neurodegenerative conditions such as Parkinson’s disease. Researcher at the University of California, San Diego School of Medicine, June 2020 Announcing a big step Toward that goal: A single dose of a new protodrug was able to transform other cell types directly into neurons. This is a feat that alleviates the symptoms of Parkinson’s disease in mouse models.

Currently, a team led by the University of California, San Diego receives a $ 9 million grant from the Parkinson’s Disease-wide Alignment Science (ASAP) initiative to advance the study and position it for the next phase of drug development. increase. ASAP is a collaborative research initiative to advance targeted basic research in Parkinson’s disease. Its mission is to accelerate the pace of discovery and pave the way for treatment through collaboration, research-enabled resources, and data sharing. The Michael J. Fox Foundation for Parkinson’s Disease Research is an implementation partner of ASAP and the issuer of grants to contribute to the University of California, San Diego campaign.

Mouse dopaminergic neurons

Above: Mouse brain before treatment. Dopaminergic neurons are shown in green. Bottom: Mouse brain after PTB antisense oligonucleotide treatment. Converts brain sustentacular cells into dopaminergic neurons (green).

A prominent professor of Xiang-Dong Fu, PhD, Cellular and Molecular Medicine, along with a prominent professor of William C. Mobley, MD, PhD, and Neuroscience, is a Principal Investigator of the project. Dr. Bing Ren and Dr. Steve Dowdy, professors of cell and molecular medicine at the University of California, San Diego School of Medicine. The team also includes researchers from the Chinese Academy of Sciences.

“This grant supports some of the most amazing advances made in the field of Parkinson’s disease. This is a game-changing strategy that hopes to improve the way Parkinson’s disease is treated.” Said David Brenner, Deputy Prime Minister of Health Sciences. “Thanks to ASAP for making these advances possible.”

The team’s work is focused on a protein called PTB, which is known to bind RNA and influence which genes are “on” or “off” in the cell. Their previous studies showed that inhibition of the gene encoding PTB directly converted several types of mouse cells into new neurons in the dish.

To inhibit the PTB of an organism, researchers have developed a virus that carries the antisense oligonucleotide sequence. It is an artificial DNA designed to specifically bind to the RNA encoding PTB, preventing translation into functional proteins and instead stimulating neuronal development. The virus infects brain cells, but it does not infect other mice from the injected mouse.

Researchers have demonstrated that a single treatment that inhibits PTB in mice transforms the natural astrocytes, which are the star-shaped sustentacular cells of the brain, into neurons that produce the neurotransmitter dopamine. bottom. Treatment restores normal dopamine levels in mice designed to mimic Parkinson’s disease. Physically, mice recover motor function within 3 months of a single treatment and remain asymptomatic for Parkinson’s disease for the rest of their lives.

Of course, mice are not humans, and the animal models used by the team do not perfectly reproduce all the essential features of Parkinson’s disease. However, they said the study provided an exciting proof of concept.

ASAP support enables researchers to optimize methods and test them in other preclinical models. They have also patented PTB antisense oligonucleotide therapy to move forward in clinical trials.

Parkinson’s disease is an increasingly exacerbating brain disorder that leads to tremors, difficulty in coordination, and difficulty walking and speaking. This condition occurs when neurons in the area of ​​the brain that control movement slowly fail to function properly and die. Normally, these neurons produce a chemical in the brain called dopamine. When neurons are damaged, less dopamine is produced, causing motor problems that indicate disease.

There is no current cure for Parkinson’s disease, but drugs and surgical treatments that can relieve some symptoms, such as drugs that raise dopamine levels or have therapeutic effects on other brain chemicals. There are several methods.

Private sector support, such as a grant from ASAP, is contributing to the UC San Diego campaign, a comprehensive university-wide fundraiser ending in 2022. Together with UC San Diego’s philanthropic partners, the university has innovative ideas, unexpected answers, life-saving discoveries and earth-changing impacts. Find out more in the University of California San Diego campaign..




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