Roche’s First-in-Class Werner Helicase Inhibitor Shows Early Promise in Phase I Cancer Trial

   

    In a meeting at the American Association for Cancer Research (AACR) Annual Meeting 2025, principal investigator Timothy Yap, M.B.B.S., Ph.D., has published the results of RO758931, a first-in-class drug that inhibits the WRN helicase, a protein essential for survival in certain cancers.

    Although target therapy is the first in a new class of drugs, it is part of a wider group of therapies targeting the DNA damage response for patients with solid tumors and genetic changes known as high microsatellite instability (MSI) or deficient mismatch repair (dMMR). These can occur in many cancer types, and most patients who have these types of solid tumors do not respond to immune checkpoint inhibitors or develop resistance during treatment. Dr, Timothy Yap states:

"RO7589831 appears generally safe and shows promising signals of anti-tumor efficacy. These are encouraging early clinical data, especially because this is a patient population that currently has very limited treatment options. This also further validates Werner helicase as an actionable target, which is exciting because many cancers are highly dependent on it for survival."

    Like other DNA damage response therapies, RO7589831 inhibits the DNA repair enzyme, Werner helicase, preventing it from working properly. This creates a buildup of DNA damage within tumor cells, leading to cell death. However, since normal cells lack MSI, they will not be affected. 

    44 patients were evaluated for safety. Most experienced mild to moderate adverse effects. The most frequent side effects are manageable and similar to those of other treatments. They include nausea, vomiting, and diarrhea. While higher doses are less tolerable, no dose-limiting toxicities were observed. Three randomized dose-level cohorts are underway to establish the optimal recommended dose for the Phase II trial in the future. 

WORKS CITED

 MBT Desk (2025). Roche’s First-in-Class Werner Helicase Inhibitor Shows Early Promise in Phase I Cancer Trial. MedBoundTimes. https://www.medboundtimes.com/biotechnology/roches-first-in-class-werner-helicase-inhibitor-phase-i-cancer-trial

Genentech (2025). A clinical trial to look at how safe and well RO7589831 works at different doses in people with advanced solid tumours, and how the body processes RO7589831. https://genentech-clinicaltrials.com/en/trials/cancer/solid-tumors/a-study-to-evaluate-the-safety--pharmacokinetics--and-a-03859.html

Unraveling the Genetic Prelude to Gastric Cancer

The article discusses research by Coorens et al., which analyzes human stomach tissues to explore the mutational landscapes across normal, precancerous, and cancerous stages. It highlights how normal gastric glands accumulate mutations over time, and how this mutational burden increases in metaplastic glands, potentially setting the stage for cancer. Normal gastric glands accumulate mutations over time primarily due to two factors: the natural aging process and the high turnover of cells. DNA replication errors can occur as cells divide to replenish the gastric epithelium, leading to mutations. Environmental factors such as diet, toxins, and even normal metabolic processes can also introduce DNA damage. These accumulated mutations can then contribute to the development of metaplasia and potentially lead to gastric cancer. This study offers insights into how early mutations in normal tissues could lead to cancer, emphasizing the importance of early detection and understanding mutational processes for cancer prevention.

The findings by Coorens et al. underscore the value of genomic surveillance in seemingly normal tissues. By identifying mutational signatures that appear early in the disease process, researchers may be able to develop biomarkers for early detection or risk assessment. This could pave the way for preventative strategies or targeted surveillance in individuals at higher risk for gastric cancer. Furthermore, understanding the mutational mechanisms at play may guide the development of therapies that interrupt the progression from metaplasia to malignancy.

Links:

https://www.nature.com/articles/d41586-025-00803-y 

https://www.nature.com/articles/s41586-021-03790-y

Shedding Light on Cancer Treatment

 Lightspeed to a Cancer-Free Era

Cancer treatments have been improving year after year leaps and bounds for the last few decades, and another milestone was hit today. A lab in Ohio State found a way to break up the structures of mitochondria by inducing light-activated electrical currents inside the cell. They dubbed the technique mLumiOpto. According to the results of the research this causes "programmed cell death followed by DNA damage." To do this they implant the genetic information of a light-sensitive protein known as CoChR, which carries a positive charge, and a bioluminescent enzyme. They follow that injection with the injection of an unnamed chemical that induces the bioluminescence, and thus activates CoChR, inducing mitochondrial collapse. To ensure that the virus doesn't target host cells, they use "well-characterized adeno-associated virus (AAV)" which has a low infectious characteristic. As the team is well versed in dealing with cancer cells, they decided to refine the process and add a promoter protein to increase the growth of CoChR in the cells. They innovatively use a monoclonal antibody that is geared to detect the specific receptors found in cancer cells. 

This research is phenomenal. I can't wait to see what cancers they are capable of treating in the future, it is unfortunate they patented the technology, and I can only hope that they are doing that so nobody else can price gouge it and that they will release the procedure for a low cost to help save lives. Building off of this could be used for non cancerous tumors possibly, depending on the cell surface receptors found in those cells, leading to a revolution in our cell-specific targeting for diseases and other maladies. Big congratulations to Ohio State for this one, as well as the researchers involved in the project: Lufang Zhou, Margaret Liu, Kai Chen of Liu's lab and Patrick Ernst of Zhou's lab, Anusua Sarkar, Seulhee Kim, Yingnan Si, Tanvi Varadkar and Matthew Ringel. All involved were from Ohio State.

Links

https://www.sciencedaily.com/releases/2024/12/241213125202.htm

https://www.biotechniques.com/cancer-research/let-there-be-light-gene-therapy-targets-cancer-cells-mitochondria/

How a DNA repair study is helping cancer studies

    DNA damage takes place when cells are exposed to radiation which can stall or hurry cell growth leading to aging and cancer. Scientists got together to study further just how damaged DNA cells are mobile. Tubules form to catch DNA breaks when a network of microtubules pushes on the nuclear envelope after DNA inside a nucleus is damaged. The formation of these tubules are promoted by the regulators DNA damage response kinases and tubulin acetyltransferase. The nuclear envelope tubules are used to repair DNA in cells but, cancer cells seem to need them the most. The study continued to analyze more than 8,500 cancer patients to reveal that "targeting factors that modulate the nuclear envelope for damaged DNA repair effectively restrains breast cancer development" (Science Daily). In aggressive cancers, tubule levels are elevated due to having more damaged DNA than average cells. It was found that when fewer tubules were present, the cancer cells were more resistant to PARP inhibitors. The enzyme PARP binds to damaged DNA, while PARP inhibitors block this action, which makes the resulting DNA impossible for cells to replicate. 

    While reading the article, various different studies were brought up and it was explained how many of these articles had been "piggy-backing" off of each other, using the last new results to find newer results. I find it refreshing to see this, especially in studies involving cancer. I thought it was super interesting to read about how each finding lead to the next, and how scientists are trying to piece everything together to hopefully help those affected by cancer. Reading about how there is a correlation found with tubules and PARP, and how certain processes, like the use of tubules, are needed more by some cells rather than others. 

 https://www.sciencedaily.com/releases/2024/04/240417120408.htm

https://phys.org/news/2024-04-uncover-human-dna-nuclear-metamorphosis.html#google_vignette 

Obesity Leads to Gamete Damage

Obesity can lead to a multitude of serious health problems. One that is not often discussed is the damage that it can cause to sperm production. In one experiment Zucker rats, chosen for metabolic characteristics that are close to our own, were examined for a variety of traits revolving around reproductive function. Twelve rats were selected from the same litter, some of which were over fed resulting in obesity. After being examined it was found that obesity caused many problems in regard to reproductive function.

               Among the things affected were the physical anatomy of the genitals, difference in organ weight, onset of puberty, and sperm production. The affects obesity had on sperm production were alarming. It was found that gamete production was significantly decreased as well as having notable damage to the DNA. The DNA fragmentation may result from cells that did not undergo apoptosis correctly and proceed to spermiogenesis. This is most likely due to a deficiency in leptin, a hormone that helps to regulate reproductive function.

These findings are startling to say the least as these hormones and receptors are also part of our own genome. As the obesity crisis continues on, we must start to worry about the damage being inadvertently done to future generations. Not only do future generation have to deal with the epigenetic effects of artificial additives and unknown consequences of GMO foods, but they may very well be damaged before conception.

Sleep Tight! Researchers identify the beneficial role of sleep

Image of chromosome dynamics(red) and neuron activity(green) in Zebrafish

Research has been done and published by the Journal of Nature Communication which studied the pattern of sleep disturbances and sleep affect our brain performance, aging, and it's roles in brain disorders. Researchers were able to successfully isolate and identify sleep in an individual chromosome using 3D time-lapse techniques. These images show how single neurons need sleep so that they are able to perform nuclear maintenance and while we sleep DNA damage levels are normalized because, while we are awake DNA damage consistently accumulates throughout the day and repairing it is less efficient while we are awake.

I think it's interesting to see how something as normal as sleep plays an important role in not only how we function on a day to day basis but, in how our brain develops. It's funny because usually, you hear people saying how without sleep they are not themselves and it's literally true.

Alcohol increases the risk of skin cancer by up to 11% by causing irreparable DNA damage

Researchers from Brown University analyzed 13 studies that compared alcohol intake with a total of 95,241 non-melanoma skin cancer cases. Just one glass of wine a day increases your risk of developing certain forms of skin cancer by up to eleven percent. 

Results reveal that for every 10 gram increase in alcohol intake per day, a person's risk of Basal cell carcinoma (BCC) increases by seven percent and cutaneous squamous cell carcinoma (cSCC)  increases by 11 percent.  BCC and cSCC are abnormal, uncontrolled growths that arise in the outer layers of the skin, but in different cell types. It has been suggested that the ethanol can metabolize into acetaldehyde, a chemical compound that damages DNA and prevents its repair. Past research has shown white wine has higher levels of acetaldehyde than beer or spirits. 

Smokers & Non-Smokers Show Different Cancer Mutation Patterns

A study explains that DNA damages offer hints to help find malignancies in different types of tissues. DNA in malignant tissues of smokers shows a mutation pattern that is significantly different from those in the malignant tissues of those that are nonsmokers. This new study explains how smoking has a correlation with various types of cancer which enhances several types of DNA damage. A mutation in our DNA can arise more naturally in someone's lifetime, but some genetic changes --such as those caused by smoking -- significantly increase the risk of certain cancers. Fortunately, scientists have recognized many patterns of DNA mutations that routinely show up the tissues of certain cancers. The identified patterns that appear over and over again in a tumor DNA, can behave as a signature of the underlying mechanism that caused the mutation, which will offer clues to how different cancers can attack.

Ludmil Alexandrov, a cancer geneticist said that although smoking's link to cancer has been known for many years, it was a mystery to him as to why smoking will increase risks of cancer like the bladder or kidney, tissues that were not exposed to smoke. Alexandrov and his team of researchers found many differences in the number of manipulated DNA signatures in the malignancies of smokers compared to those that had the same type of cancer but did not smoke. Smoking can leave permanent mutations, it destroys the genetic material in many cells in the body. Alexandrov collected DNA from more than 5000 people which represented 17 cancer for which smoking was a known risk factor. Almost half of the samples were from smokers. Signature 4 was mostly found in the people who smoked but occurred far less in nonsmokers. Signature 4 showed up in cancers of the oral cavity, but researchers were not sure why these tissue's which are directly exposed to smoke didn't have a heavy mutational load. DNA damage in smokers differed from those that didn't smoke in an another suite of mutation known as signature 5. The cause of signature 5 is still unknown, but researchers did determine that the amount of signature 5 mutations is like a clock, it increases with age. Researchers also took into account the amount of tobacco smoked, they discovered that the number of mutations in some diseases was linked to smoking a pack a day for one year. A pack a day for one year leads to 150 mutations in a lung cell, 97 in a larynx cell, 39 in the pharynx, 23 in the oral cavity, 18 in the bladder and 6 in a liver cell. 

"When someone has cancer, we can only see what is happening right now, we do not know what happened 20 years ago when that cancer was just one cell," says cancer biologist GerdPfeiffer. I completely agree with Pfeiffer on that because these signatures can give us a clear idea of what might have happened years ago.

Smoking is actually giving one benefit, and that is to figure out why it increases the risks of cancer. With this idea, we can make more experiments on how it can decreases the risks too.

The Difference Between Cancer Mutation Patterns in Smokers and in Non-Smokers

     Gene mutations in any organism can have several causes. Smoking, however, has been known to increase the risk of around 17 cancers, including lung cancer, bladder cancer, kidney cancer, and many more. Tobacco smoke is a complex mixture of chemicals, at least 60 of which are carcinogens. A new analysis shows that DNA in cancerous tissues of smokers are different from those in cancerous tissues of non-smokers. Cancer geneticist Ludmil Alexandrov and his international research team conducted an experiment in which they analyzed and examined mutational signatures and DNA methylation in DNA extracted from 5000 genome sequences, half of which were from smokers. What showed the increase in cancer risks in smokers were the mutational signatures 2,4,5,13, and 16. 

    
  
     Signature 4 mutation signals damage to guanine and it appears in DNA of cells which were exposed to chemicals from burnt products, such as tar in cigarette smoke. This signature was found in non-smokers' tumors, but less often. Smokers with lung squamous cancer, lung adenocarcinoma and larynx cancers had high numbers of signature 4 mutations, while cancers of oral cavity, pharynx, and esophagus had much less signature 4 mutations. Even though the reason why these tissues didn't have as much signature 4 mutations, despite being the most directly exposed to smoke, is unclear, the team speculates that these tissues might metabolize smoke differently.

     Another difference observed between the smoker's damaged DNA and that of non-smokers was the presence of signature 5 mutations. This signature normally shows up in all cancer types but its cause is still unknown. However, it is known that it increases with age and the analysis revealed that the more a person smoked, the more signature 5 mutations were present. Smokers with lung adenocarcinoma also appeared to have more signature 2 and 13 than non-smokers with the same disease. These could have resulted from overactive DNA editing machinery. However they are found in many types cancer and it's still unclear how smoking influenced the increase in these signatures. Signature 16 has only been found in liver cancer tumors, but it was in a higher number in smokers' damaged DNA than in those of non-smokers. It's correlation to smoking is also unknown.

     The researchers took into account the pack years smoked (1 pack year = one pack of cigarettes per day per year) and found a positive correlation between pack years and the number of mutational signatures. This information helped them calculate the mutations caused by smoking for each cancer type in the tumors they researched. The results were that one pack year leads to 150 mutations in a lung cell, 97 in a larynx cell, 39 in the pharynx cell, 23 in the oral cavity cell, 18 in the bladder cell, and 6 in a liver cell.

     I think that this information is very important for the public, so that it can bring better awareness to how harmful smoking is and how important it is to help treat people with smoking addictions. I hope that more answers can be found about how the signatures mentioned in the previous paragraph cause cancer and what the correlation between these mutations and smoking is, because this information can also help identifying the causes of other cancers due to these mutations.

Links:

• https://www.sciencenews.org/article/cancer-mutation-patterns-differ-smokers-nonsmokers

• http://science.sciencemag.org/content/354/6312/618.full

Vital Information about Mechanisms Governing DNA repair

Damage of DNA can lead to serious diseases like cancer. The damage can lead to inactivation or not properly regulated genes. With DNA repair however, cells can survive after damages. Antoine Simoneau of Dr. Hugo Wurtele's laboratory at  Maisonneuve-Rosemont Hospital has found some very important information about the DNA repairs, that could eventually lead to more research that could help with the cure of cancer.

HDAC Structure

While using yeast as their model system they found the mechanisms that influence cell growth with the presence of a certain class of HDACs (histone deacetlyases). The DNA can adopt to a small enough size to be able to wrap around the histones and form chromatin. The cells can now chemically modify the histones and the chromatin can change the structure to be able to control various functions of the DNA. This entire process has been show to be a promising treatment for cancer. In particular, class III HDAC which influences cellular processes involved in carcinogens and response to chemotherapy agents. These agents strongly block the rapid multiplication of cells by preventing the normal functions involved in the response of DNA damage spontaneously generated by cellular metabolism.
With this new information on basic research there is now an open door for more research and eventually clinical uses. Dr. Wurtele's lab will further their research to determine how this new class of drugs inhibits cancer cell growth.

Though there is not much research on this topic it does seem promising for cancer. I would like to see how this research works toward different types of cancer and the rapid growth of certain cell growth. The new class of drugs I think will be a great step forward toward the inhabitation of the cancer cells or at least a possibility of slowing the growth down.

The genes that could one day increase lifespan in humans

     After ten years of research by the Buck Institute for Research on Aging and the University of Washington has identified 238 genes that increase the replicative lifespan of S. cerevisiae yeast cells when removed.  This was the first time 189 of these genes were linked to aging.  The results found could provide new genomic target that could improve human health.

     Dr. Matt Kaeberlein, PhD from the Department of Pathology at the University of Washington and his team began the painstaking process of counting and examining 4700 yeast strains of yeast each with a single gene deletion.  Each strain had the daughter cell and mother cells separated and count to see how many times the mother cell divided. 

     The effort produced the information about how different genes and their pathways modulate aging in yeast. The deletion of gene LOS1, which helps relocate transfer RNA that brings amino acid to ribosomes to build proteins, produced huge results. LOS1 is influenced by a master switch the is associated with caloric restriction and increase lifespan, mTOR; also LOS1 influences another gene Gcn4 that helps govern DNA damage control.
     This research is only part of the process to map the relationship between the gene pathways that govern aging.  A number of these age-extending genes are found in roundworms and humans alike so the deletion of these genes could also prolong the lives of human eventually.  The researchers hope that this research will produce new therapies.
    "Almost half of the genes we found that affect aging are conserved in mammals," said Dr. Kennedy. "In theory, any of these factors could be therapeutic targets to extend healthspan. What we have to do now is figure which ones are amenable to targeting."(1)
      I am a little afraid of this to come true.  I couldn't think about what would happen if more humans were able to extend their lives.  How many people would like to extend their lifespan if they had any of disease or a disability that would affect how they live. Imagine if you were able to live to be over 100 but you happened to lose the use of your legs at later in your life; would you want to live longer if your quality of life starts to decline.

http://www.sciencedaily.com/releases/2015/10/151008142230.htm
http://www.buckinstitute.org/

1. Buck Institute for Research on Aging. "Mapping the genes that increase lifespan: Comprehensive study finds 238 genes that affect aging in yeast cells." ScienceDaily. ScienceDaily, 8 October 2015. <www.sciencedaily.com/releases/2015/10/151008142230.htm>.

Has mRNA been looked over too much?

Everyone knows that damage done to DNA is a problem. However, no one assumed that the damage done to mRNA would ever be a problem. Well they were very wrong. A group of scientists at Washington University in St. Louis discovered one very important factor that may be key to understanding diseases like Alzheimer's.
"Everybody thought, 'Why care about the messenger RNA? These molecules have high turnover rates and are quickly degraded, so what does it matter if one is damaged?'" said Hani Zaher, PhD, assistant professor of biology in Arts & Sciences at Washington University in St. Louis.

"In organisms like E. coli or yeast, that's probably true," Zaher said. "You don't have to worry about mRNA because it turns over really fast. But in neurons you can't use that argument because an mRNA can persist, in some cases for days. And if that mRNA is really damaged it can become a big problem." He also stated that Under normal conditions only about 1 percent of the cellular mRNAs are oxidized, but if you have oxidative stress, for whatever reason, a higher percentage can be damaged.

One of the hallmarks of Alzheimer's is oxidative stress, and studies have shown that in people with advanced Alzheimer's, half of the RNA molecules in the neurons may be oxidized."

When the team at Washington fed oxidized mRNA to ribosomes it appeared that they jammed and stopped. It was said that a frozen ribosome could be rescued by factors that released it from the mRNA however, later chewed up and damaged. With these certain factors missing, damaged mRNA accumulated in the cell, just as it does in Alzheimer's.

It's known that when DNA is transcribed to mRNA, there is a mistake 1/10,000 times. This means when the mRNA is translated to protein, there might be an error 1/1000 times. To test the theory the team was given mRNA transcripts to ribosomes. They damaged one letter in a three-letter mRNA coding unit, oxidizing a G (the base guanine), to create what is called 8-oxo-G.

"We expected that we might get aberrant proteins," Simms said. "But the ribosome didn't make mistakes. It just stopped. It couldn't deal with the mRNA at all"

Because of their finding, they wanted to go further into detail. Simms built a longer 300-nucleotide mRNA to use. And instead of adding the damaged mRNA to a reconstituted bacterial system, she put it in extracts of plant and animal cells. They wanted to rear it with something called "no-go decay"What they found made them question whether or not if oxidized mRNA was the target. To further test everything they turned to yeast. The yeast ribosomes jammed on the oxidized mRNA but were rescued by no-go decay…This caused very little damaged mRNA to accumulate in the cell.  Because of this discovery, Simms was able to delete a gene for a factor that releases the ribosomes from the mRNA when it jams. When she did that, the level of oxidized mRNA went up so she then deleted a gene factor that is recruited to degrade the mRNA after the ribosome is released, and again the level of oxidized mRNA rose. Without no-go decay, the cells were clearly in trouble.

Zaher said "The system that translates mRNA into protein is highly conserved, so what's true for yeast is probably true for people as well… Is oxidized mRNA implicated in disease? Science recently published work showing that mice with a double defect in their translation system have severe neurodegenerative disease”

With the information they now have, who knows how far they can go to repair these damaged mRNA in patents with Alzheimer's? After that who knows how far it could go with all neurodegenerative diseases. This is an amazing discovery and I think a lot of progress will be made within the next couple of years.

Article: http://www.sciencedaily.com/releases/2014/11/141113122235.htm

Asthma Causes Genetic Damage in Circulating Blood

     Until now, doctors have thought that the genetic damage caused by asthma was limited to the lungs. However, recent research at University of California, Los Angeles has shown that it negative affects the genes of peripheral, or circulating, blood in the body. 

     The study was conducted in an animal model that mimicked human asthma. Robert Schiestl, the senior author of the research, was the first to asses the role of IL-13 in genetic damage to cells. IL-13 is interleukin 13, a type of cytokine known to mediate inflammation. The research focused primarily on the over-expression of this IL-13. The results from Schiestl's studies have shown that IL-13 increases important elements of the inflammatory response, such as reactive oxygen species molecules. The research team found that reactive oxygen species-derived oxidative stress induced genetic damage with four main types of systemic effects in the peripheral blood. They are oxidative DNA damage, single and double DNA strand breaks, micronucleus formation, and protein damage. All of these effects cause the chromosome to become unstable, which can result in a variety of other diseases. 

     Schiestl and his team hope to use chemicals to repair the DNA of damaged cells. Their goal in doing this is to determine whether doing so will make asthma less damaging by reducing genetic instability in circulating blood. 

Robert Schiestl is a professor of pathology and radiation oncology at the David Geffen School of Medicine at UCLA.

     I found this article interesting because it is scary to learn that asthma affects the whole body more drastically than people think. Many people experience asthma and do not have it properly treated. It effects more than 150 million people throughout the world. This research shows how serious the disease can be. 

Article: http://www.sciencedaily.com/releases/2014/11/141104153551.htm

DNA Repair Could Lead to Better Cancer Treatment

Researchers from the University of Alberta have made a simple discovery which allows for better understanding to how DNA repairs itself.  DNA can become too damaged, which therefore can lead to cancer.  For years many scientists believed two key proteins involved in DNA repair operated in indetitcal ways.  Mark Glover and his team of researchers discovered that how the proteins actually operate and communicate is very different, which could lead to better cancer treatment.  A protein known as BRCA1 acts like a hallway monitor, constantly scanning DNA for damage.  Right when damage is detected, the protein figures out exactly what help is needed and signals other proteins for help.  Another protein called TopBP1 makes sure DNA can copy itself when needed and when problems occur with this process due to DNA damage, the protein also calls other proteins for help.  Glover states, "The two proteins may be related and look very similar, but their roles and the way they communicate are in fact very different, which was surprising to us.  Each protein plays a role in recognizing damaged regions of DNA, but the problem they each solve is different".  With this new information, it is possible that cancer treatments can become more advanced than ever before.  Glover also adds, "Maybe some of these ideas could ultimately translate into less radiation or chemotherapy needed for patients, if the treatment can be more targeted".  There is still much to be discovered and researched but this new information is a big step in the right direction in my opinion.   

http://www.medicalnewstoday.com/releases/265967.php
http://www.nature.com/scitable/topicpage/dna-damage-repair-mechanisms-for-maintaining-dna-344

Neurodegeneration Linked To ADP-Ribose

In European news, EMBO.org (European Molecular Biology Organization) reports that researchers have identified an enzyme that removes ADP-ribose modifications from proteins by studying a genetic mutation that causes neurodegenerative disease in humans. These findings, suggest that not only addition but also removal of ADP-ribose from proteins is essential for normal cell function. Poly ADP-ribose or PARP chains play key roles in the repair of cellular DNA damage, and in the control of gene expression and cell death. Pharmacological drugs called PARP inhibitors prevent the addition of ADP-ribose or their polymers to proteins. Several of these drugs are undergoing clinical trials for the treatment of different types of cancers.

A breakthrough in the study came when collaborators from the National Institutes of Health, USA and Ludwig Maximilians University, Munich teamed up with clinical geneticists at the Human Genetics Research Center at St. George's University of London lead by Reza Sharifi. She stated,

“By studying genetic mutations in a group of patients with severe neurodegenerative disease, we found a gene that was mutated in a family that had several cases of severe progressive neurodegenerative and seizure disorder.”

She continued to explain that the product of this gene, named TARG1 (for terminal ADP-ribose protein glycohydrolase), exhibited the long-sought-after enzyme activity that fully removes ADP-ribose from proteins, and was further required for the rapid increase of cells and response to DNA damage.

The full research article can be found at The EMBO Journal.

If you read further into the linked articles it talks about how researchers found a gene that was mutated in a family that had several cases of severe progressive neurodegenerative and seizure disorder. The findings revealed that the attaching and removing chains of ADP-ribose to proteins are important to cell survivability and DNA repair. I find it simply amazing that they can analyze patients with a family history of neurodegeneration to gain a better understanding of this mechanism and perhaps give them a better understanding of what is happening to them and eventually, I believe, how to correct it. They are getting ever closer to finding out the exact enzyme(s) that may be responsible for it.