Stem Cell Clinic

What Causes a Weakened Immune System? – Self

Youve probably heard a lot about how important your immune system is, especially over the past few years. Phrases like herd immunity and immunocompromised proliferated in official public health updates, news stories, and health care centers as experts navigated all the uncertainties of the COVID-19 pandemic. Now, we know that the virus can affect anyone, but it can lead to particularly risky complications for the most vulnerable people in our communities.1

Of course, theimmune systems job is to protect your body fromall invaders that may be harmful, not just certain viruses: When functioning properly, it alerts your body to a wide range of potential threats and helps it respond accordingly. However, some people have dysfunctional immune systemswhich are also known as weakened or compromised immune systemsthat cause their bodies protective response to be under- or overactive, perJohns Hopkins Medicine.

Theres no exact figure for how many people live with weakened immune systems, but its safe to say its in the millions,Leonard Calabrese, DO, a rheumatologic and immunologic disease expert at the Cleveland Clinic, tells SELF. Some research suggests at least 7 million adults in the United States are immunocompromised, per theCenters for Disease Control and Prevention (CDC).

Below, experts explain the factors that can break down the immune systems defenses, the common symptoms associated with compromised immune systems, and what kinds of treatments are available to help.

What is a weakened immune system, exactly?

Yourimmune system is an intricate network of cells, tissues, and organs (as well as the substances they make) that, generally speaking, fight disease and infection, according to the National Institutes of Health (NIH). White blood cells may come to mind, but there are lots of body parts that play important roles in your immune health, like your skin, lymph nodes and vessels, thymus gland (which makes white blood vessels), spleen, tonsils, and bone marrow, among others.

The immune system is generally broken down into two parts,Scott Weisenberg, MD, an infectious disease specialist at NYU Langone Health, tells SELF. These are called the innate (or inherited) and the adaptive (or acquired) immune systems. The major difference between the two is that youre born with the former and your body develops the latter.2 Theinnate immune system is the first to respond to an invadersuch as a harmful germby surrounding it with protective cells and, if all goes as planned, killing it. Theadaptive immune system supports your innate response by producing proteins called antibodies.2 These are designed to counter a specific threat, like certain viruses or bacteria, should your body be exposed to them and need backup in the future, perJohns Hopkins Medicine.

Problems can occur when the immune system either doesnt respond enough or responds too strongly, Dr. Calabrese says. A compromised immune system fails to either detect danger or [reacts] aggressively and causes collateral damage to our systems, he explains.3 Its worth noting that problems with the immune system exist on a spectrum, Dr. Calabrese adds. The potential health risks posed by a weakened immune system arent the same if youre comparing one person who, for example, has moderate allergies, to someone whod recently had an organ transplant. Theyre hardly in the same category, Dr. Calabrese says.

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What causes a weakened immune system?

Any number of health issues, such as mild asthma, can affect your bodys ability to fight disease and infectionand certain lifestyle factors, like smoking tobacco and not getting enough sleep, can also interfere with your bodys ability to stay balanced and heal, theCDC says. However, there are several major factors that can compromise your immune systems defenses. These include:

Autoimmune diseases are characterized by a malfunctioning immune response; essentially, your body goes a bit rogue and starts to attack its healthy cells, tissues, and organs, according to theNIH. There are more than 80 autoimmune diseases that experts know of, includingrheumatoid arthritis,type 1 diabetes,lupus, and many more; these conditions are thought to impact at least 24 million people in the United States, while an additional 8 million are estimated to have blood markers that point to their susceptibility of developing one of these disorders, per the NIH.

Autoimmune diseases in general compromise a persons immune system by attacking the body. On top of that, to help a person manage the symptoms caused by their conditionmany of which can severely affect the persons quality of lifeexperts often recommend medications called immunosuppressants, like steroids orbiologics. These medications can be life-changing for some people but, in turn, the treatments can weaken the entire immune system or just a specific part of it, according to theAmerican Academy of Allergy Asthma & Immunology.

People who receive a bone marrow, stem cell,4 or organ transplant will also have a weakened immune system during the first few weeks after the procedure because the bodys white blood cell count is depleted, increasing the risk of potential infection. Immunosuppressants are also commonly prescribed following these procedures because they help the body accept the transplant and prevent it from attacking normal (and vital) tissues, according to experts at theUniversity of Pennsylvania Health System.

Primary immunodeficiency diseases (PIDDs)also commonly known as inborn errors of immunityare rare genetic disorders that cause at least one part of a persons immune system to malfunction, according to theNIH. There are nearly 500 known PIDDs, and theyre typically characterized by repeated or severe infections.5

There are a variety of other health conditions including type 2 diabetes, liver or kidney diseases, alcohol use disorder, and HIV/AIDS, among others,that can compromise your immune system, theCDCnotes. Any form of cancer can also weaken or suppress the immune system, per theAmerican Cancer Society, but the associated treatments, which tend to be really hard on the body, can mess with immune defenses as well. These can include chemotherapy, radiation, surgery, stem cell transplants, and more.

These conditions are known as secondary immunodeficiencies, which are far more common than primary immunodeficiencies. Secondary immunodeficiencies are not a result of geneticerrors, but rather a variety of potential factors that can impact a persons once-normal immune system, like an infectious pathogen, certain substances, and environmental changes, for example.6

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What are some common signs of having a weakened immune system?

Immunocompromised people tend to get infections more often, or they may get severely ill from infections that people with healthy immune systems can recover from more easily, Dr. Weisenberg says. This means the infections may be harder to treat or last longer than expected.

People with weakened immune systems are also more likely to experience symptoms triggered by germsincluding viruses, bacteria, and fungithat arent normally seen in people with healthy immune systems. For example, Dr. Weisenberg says, a serious infection causedby the fungus Pneumocystis jiroveciiis usually only detected in people with weakened immune systems.

Frequentdigestive issues, like diarrhea, constipation, and gas, are also worth noting, per theUniversity of Pennsylvania Health System. (One theory that might explain this: Research suggests a large portion of the immune system lives in the gastrointestinal tract. In fact, up to 80% of your immune cells are found in the gut.7)

Minor woundssuch as cuts and scrapesmay also be slower to heal, since healthy immune cells are needed to shepherd the recovery process.

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What kinds of treatments are available for people with weakened immune systems?

The best treatment plan will vary depending on what, exactly, is compromising a persons immune system, Dr. Weisenberg says. In general, many treatment plans are focused on symptom management and infection control. Some people may also benefit fromintravenous immunoglobulin therapy to help replenish protective proteins, namely antibodies, and prevent infection, he adds. Immune system replacement in the form of stem cell or bone marrow transplants, as well as gene therapy, are also options depending on the cause and severity of a persons condition,as SELF previously reported.

Even with these care options, its important to recognize that people with weakened immune systems often depend on herd immunity or community immunity. This is achieved when a majority of a population has a sufficient level of immunity against aspecific infectious disease through vaccination or prior infection and recovery. This helps reduce the person-to-person spread of a pathogen, ultimately protecting vulnerable people who cant afford to get sick due to a higher risk of complications or who dont respond to or cant receive certain vaccines.8

Community immunity is extremely important,Dusan Bogunovic, PhD, a professor of microbiology at the Icahn School of Medicine at Mount Sinai in New York City, tells SELF. This can be a lifeline for many.

There are other common-sense strategies that slow infection in our communities, too, like frequent handwashing and masking up in crowded spaces. It takes a collective, conscious effort: Together, we can help protect the millions of immunocompromised people we live, work, and hang out with every day.

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What Causes a Weakened Immune System? - Self

Olema Oncology to cut 25% of staff, says it will focus on late-stage … – Endpoints News

Olema Oncology will let go of a quarter of its workforce, as well as two top executives, as the biotech works to keep alive work on an experimental breast cancer drug that has so far been a disappointment.

The cuts will affect workers in R&D and corporate functions, the company said in a press release Thursday. Also out are CBO Kinney Horn and Cyrus Harmon, a co-founder of the company and its chief research officer. Harmon will stay as a member of the board. The company had 83 full-time employees as of Jan. 31, according to a financial filing.

CEO Sean Bohen has led the company since he left the top medical spot at AstraZeneca. The job cuts will let the company focus resources on OP-1250, the breast cancer drug that has worked and struggled with to move forward for years.

Given the challenging equity market environment, we made some difficult decisions regarding our organization and earlier-stage programs, Bohen said in the press release.

The company is worth a fraction of its value from when it IPOed in 2020, and the shares were trading around $50 a share. In November 2021, it announced results from its Phase I/II trial of OP-1250 that greatly disappointed investors because of the low response rate in advanced ER+/HER2- breast cancer. The stock plunged and has never recovered, and now trades around $4 a share.

The San Francisco-based biotech says it has enough cash to last into 2025. It reported $204.4 million in cash, equivalents and marketable securities as of the end of last year and a net loss of $104.8 million.

It plans to start a Phase III trial of OP-1250, an estrogen receptor antagonist, in the second half of the year, as a second- and third-line treatment for metastatic breast cancer. And it has Phase II trials that it expects will report out this year, both as a monotherapy and in combination with Pfizers Ibrance.

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Dr. Shah on the Safety of LV20.19 CAR T-cell Therapy in R/R MCL – OncLive

Nirav N. Shah, MD, associate professor, Medical College of Wisconsin, discusses the safety of the lentiviral bispecific CAR T cells targeting CD20 and CD19 B-cell antigens (LV20.19 CAR), as well as future efforts from a phase 1/2 study (NCT04186520) of the product in patients with relapsed/refractory mantle cell lymphoma (MCL).

At the 2023 Transplantation and Cellular Therapy Meetings, investigators presented data on the single-center, prospective study that examined 14 patients. The trial met its primary end point with an overall response rate (ORR) of 100% at day 28, including a 71% complete response (CR) rate. At day 90, the ORR remained at 100%, and the CR rate improved to 92%.

Regarding safety, findings for the use of LV20.19 CAR in patients with MCL have been in line with other histologies treated with the agent, Shah says. Thirteen of 14 patients (93%) experienced grade 1/2 cytokine release syndrome (CRS); however, there were no instances of grade 3/4 CRS. Two patients (14%) had grade 3/4 immune-effector cell-associated neurotoxicity syndrome (ICANS), and 1 patient (7%) had grade 1/2 ICANS.

Shah notes that no patients required intensive care unitlevel care in the first 28 days; however, 1 non-relapse mortality was reported in a high-risk patient who previously received an allogeneic stem cell transplant for MCL, then subsequently relapsed and received CAR T-cell therapy, Shah explains. This patient died from gram-negative sepsis at day 46, Shah adds. Beyond the lone non-relapse mortality, LV20.19 CAR was well tolerated, and all patients remained alive at data cutoff, Shah continues.

The safety and efficacy profiles of this agent are favorable compared with currently available agents, Shah notes. Investigators next hope to evaluate LV20.19 CAR in patients with relapsed/refractory MCL in a multicenter setting, Shah concludes.

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Investigating KRAS/TP53 Co-Alterations in Pancreatic Cancer – Targeted Oncology

Jashodeep Datta, MD, a surgical oncologist at Sylvester Comprehensive Cancer Center and assistant professor of Clinical at the University of Miami Miller School of Medicine, explains KRAS co-alteration in patients with pancreatic cancer.

Many pancreatic tumors have co-alterations in KRAS and TP53, explains Datta. The reason for these co-alterations is unknown, and oncologists also do not have a clear picture of how this effects the disease. These questions were explored preclinically and warrant further study.

0:07 | We are very interested in understanding the chasm that exists between the genotype of pancreas cancer and the virulent phenotype of pancreas cancer. What makes it so hostile for patients? To do that we approach this from the genome of the pancreatic cancer cell, which is really the incipient event in pancreatic tumorigenesis. And what's very interesting about pancreas cancer is compared with all of the cancers, if you look across the Cancer Genome Atlas, pancreatic cancer is the number one cancer that has cooperated mutations of KRAS and TP53.

0:46 | We really want to understand if there is a biologic basis for that, and what are the downstream repercussions of that. The was really the basis of this study. The most important finding that really paved the way for the remainder of our study was our finding, using a cohort of 250 patients from the University of Miami, as well as validation in two independent datasets, one from the Cancer Genome Atlas, as well as one from an international molecularly annotated data set the ICGC, where we showed that patients who had quadrate mutations in KRAS and TP53 had worse survival and worse prognosis compared with patients who had mutations in either the carrier s gene alone. And they had may have other mutations, but not TP53, or TP53 mutations alone, but not KRAS. So, this really paved the foundation for the remainder of the study.

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Simultaneous advice from FDA and EMA? Very few companies go … – Endpoints News

Amgen wants to open up conversations around relationships and asthma, and is enlisting a well-known therapist and author to help. Lori Gottlieb, a New York Times bestselling author and therapist, is leading the discussion in online videos with people living with asthma, offering advice and guidance directly to them as well as on the campaign website.

The Air Between Us All campaign was created after a survey Amgen conducted with partner Asthma and Allergy Foundation of America (AAFA) found more than half (56%) of people with asthma dont share that they have it unless they have to. And while almost half (46%) agreed that asthma can interfere in important moments with significant others, about the same number (47%) felt that family, friends and significant others dont consider their asthma when planning gatherings.

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Medicaid Expansion Moves Forward In New Hampshire With … – Kaiser Health News

The state Senate gave preliminary approval to continue the expanded Medicaid program and make it permanent, AP reports. Meanwhile, in Wisconsin, Republican lawmakers blocked a plan by the governor to mandate student vaccinations against meningitis and chickenpox.

AP:New Hampshire Senate Backs Medicaid Expansion BillA unanimous New Hampshire Senate gave preliminary approval Thursday to continuing the states expanded Medicaid program and making it permanent. The 24-0 vote to send the bill to the Finance Committee highlighted the Legislatures evolution on what initially was a tough sell when lawmakers first considered expanding health care coverage for low-income residents. (Ramer, 3/9)

AP:Republicans Block Meningitis, Chickenpox Vaccine MandatesWisconsin Republicans blocked Gov. Tony Evers plan Thursday to require student vaccinations against meningitis and tighten student chickenpox vaccination requirements. The Legislatures GOP-controlled rules committee voted 6-4 to block the proposal. All six of the panels Republican members voted to stop the policy. The vote comes two days after a lengthy public hearing on the policy changes that saw parents complain that the new requirements trample their liberties. The committee blocked the proposal last legislative session as well. (Richmond, 3/9)

More health news from across the U.S.

KHN:Montana Considers New Wave Of Legislation To Loosen Vaccination RulesWhen Deb Hornings youngest daughter was 5, she got her measles, mumps, and rubella shot like many other kindergartners. But unlike many other moms, Horning had to stay away from her daughter for a week after the shot. Horning, 51, was diagnosed in 2014 with acute myeloid leukemia, an aggressive cancer the five-year survival rate for those older than 20 is 27%. Horning had been through chemotherapy and a stem cell transplant, which severely weakened her immune system. Because the MMR vaccine contains live virus, she couldnt get the vaccine herself and had to temporarily avoid her vaccinated daughter. (Larson, 3/10)

Oklahoman:Psilocybin Therapy Research Program Approved By Oklahoma HouseHouse Bill 2107 was advanced by the Oklahoma House of Representatives on Thursday and can now be heard in the Senate. Its author, state Rep. Daniel Pae, R-Lawton, said Texas already has adopted similar legislation, and it's also being considered in Montana, Missouri, Pennsylvania and Arizona. (Denwalt, 3/9)

AP:Dealers With Cancer Beg For Atlantic City Casino Smoking BanTammy Brady began her career as an Atlantic City casino dealer at the age of 18. Now 55, she has stage 2 breast cancer. While Im not sure we will ever know the exact cause of my illness, I cant help but wonder if it would have happened if the casinos hadnt forced me to work in second-hand smoke, said Brady, who works at the Borgata casino. Holly Diebler, a craps dealer at Tropicana, is undergoing chemotherapy for throat cancer. I dont even know how long Im going to live, she said. I love my job; I dont want to leave it. But all my oncologists have told me this is a life-and-death choice. (Parry, 3/9)

Capitol News Illinois:Illinois Residents Concerned About Changes To Choate FacilityFamilies of patients at Choate Mental Health and Developmental Center, along with workers and community leaders, reacted with concern after the states announcement this week that it plans to relocate more than 120 residents from the troubled state-run facility in southern Illinois. Rita Burke, whose 53-year-old son has lived at Choate for more than 30 years, said Illinois Department of Human Services Secretary Grace Hou and two other senior state officials called her on Saturday evening to inform her of their plans. (Hundsdorfer and Parker, 3/9)

Environmental health news from Ohio and Indiana

The Washington Post:Senators Grill Norfolk Southern CEO On Toxic Ohio Train DerailmentNorfolk Southerns communication failures left emergency responders scrambling to prepare for a massive plume of toxic chemicals after a train operated by the company derailed and threatened to cause an explosion in East Palestine, Ohio, some witnesses and lawmakers told Congress on Thursday. Pressed by senators at a three-hour hearing on the Feb. 3 derailment, Norfolk Southern CEO Alan H. Shaw apologized for the disaster but stopped short of guaranteeing certain specific cleanup and safety measures, such as paid sick days for his employees or funding for East Palestine residents possible medical expenses. (McDaniel, Duncan, Wang and Dance, 3/9)

The New York Times:Health Concerns Mount In East Palestine Weeks After Ohio Train DerailmentMedical guidance is sparse. The long-awaited state health clinic sent to East Palestine weeks after the spill at first offered only questionnaires and did not have a doctor on hand. Local primary care physicians, booked for weeks, say that without more toxicology data, they arent equipped to diagnose chemical poisoning, so they are simply treating symptoms with ibuprofen and ointment. (Baumgaertner, 3/9)

Indianapolis Star:Plan To Protect Firefighters From Toxic Chemical Leaves Out OthersScientists, lawmakers and government officials across the country are trying to figure out what to do about PFAS, a toxic cancer-causing chemical. In Indiana, that focus has primarily centered on firefighters. Those in the fire service have a higher risk of exposure to the harmful chemical: It's been found in their gear as well as foam they use to put out fires. Firefighters also have higher rates of cancer, particularly some types that are linked to PFAS exposure, compared to the general population. (Bowman, 3/10)

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Medicaid Expansion Moves Forward In New Hampshire With ... - Kaiser Health News

Collaboration Propels Research on Untreatable Neurodegenerative … – Harvard Medical School

To be sure, a lot more work is needed to turn the ASO into a drug that can be safely tested on humans in clinical trials but its very existence demonstrates the lightning-quick pace at which therapeutics research can advance when scientists with complementary expertise work together.

Moreover, the work contributes to a growing field of research on ASOs, which are the basis of a new class of therapies that may be especially useful for treating thorny neurodegenerative diseases and other conditions that stem from genetic mutations, including certain types of cancer and epilepsy.

In recent years, scientists have become increasingly interested in the therapeutic potential of ASOs, which are short, single-strand sequences of synthetic DNA or RNA built in the lab.

The idea is that researchers design an ASO to correct specific protein deficiencies or malfunctions by binding to a particular stretch of RNA transcribed from the gene of interest.

This binding can cause the gene to be expressed at higher or lower levels, thus affecting the production of proteins linked to various physiologic functions.

Perhaps the most well-known ASO to date is a drug called nusinersen, which was approved by the Food and Drug Administration for spinal muscular atrophy in 2016.

Patients with spinal muscular atrophy have a mutation on both copies of their survival motor neuron 1 (SMN1) gene, which causes reduced production of the associated survival motor neuron (SMN) protein.

SMN is the essential fuel for motor neurons in the brain stem and spinal cord that control voluntary muscle movement. The protein deficiency causes patients to experience profound muscle weakness and absence or loss of muscle function that gets worse over time.

Nusinersen is injected into the spine and travels to the brain, where it binds to a section of RNA transcribed from the SMN2 gene in brain cells. SMN2 is closely related to SMN1 but typically produces only a small amount of SMN protein.

Once it binds, nusinersen causes SMN2 to produce more of the protein, thus compensating for what the SMN1 mutation suppresses.

Nusinersen was an overwhelming success it was extremely effective in these patients and so a lot of people became very excited about ASO technology, Park said.

One of those people was Yu, who wondered whether he could design an ASO to treat Mila, a six-year-old girl with a rare, fatal neurodegenerative disease called Batten disease.

Yu and his team figured out that in her case, the disease was caused by a known mutation on one copy of the neuronal ceroid lipofuscinosis 7 (CLN7) gene, combined with another mutation on the other copy of the gene.

As a result of this duo of mutations, the childs body could not produce enough of the CLN7 protein, leading to widespread and worsening nervous system problems, including seizures, poor coordination and balance, and muscle spasms and weakness.

In a matter of months, the researchers were able to create and test a personalized ASO called milasen that targeted the second gene mutation responsible for her disease.

As they had hoped, Milas symptoms improved during treatment: she had fewer seizures and she was better able to swallow and hold up her neck and body.

Mila died in 2021, but the researchers published their results in The New England Journal of Medicine as proof of concept that it was possible to create a safe and effective personalized ASO quickly.

Meanwhile, Park and his research fellow at the time, Jinkuk Kim, were embarking on a journey of their own.

As a computational biologist, Park develops algorithms that analyze human genomes and look for interesting anomalies or trends something he had been doing mostly in the context of cancer.

However, Jinkuk had an interest in ASOs and, more specifically, in finding gene mutations linked to neurodegenerative diseases that could be good targets.

Kim and Park began using their computational tools to analyze human brain sequences publicly available through the National Institutes of Health.

They were looking for something specific: genes in which a mutation on only one copy (versus both copies) is enough to alter protein production and interfere with normal function.

Eventually, they hit on GRN, a gene in which a single mutation on one copy causes brain cells to make less of a protein called progranulin.

Crucially, this GRN mutation is implicated in around 15 percent of cases of FTD a form of dementia often diagnosed in patients between 45 and 65 years old characterized by a loss of cells in the frontal and temporal lobes of the brain.

We had the idea that we could design an ASO that would impact the transcript of this gene in such a way that progranulin production would increase, Park said.

However, he and Kim knew that they needed to take their idea out of the computer and into the lab for testing so Park reached out to his old friend Yu.

When the researchers met to discuss the project, Kim asked Yu if he had ever heard of a drug called nusinersen.

Yu couldnt help but laugh at the sheer serendipity of the situation.

I said, Actually, Ive been doing nothing but studying nusinersen as quickly as I can for the last six months, because we are working on making a drug like it for our patient, Yu recalled.

With that, Park, Kim, Yu, and Yus research fellow Yu-Han Huang threw themselves into developing molecules to target the gene responsible for a significant number of FTD cases.

We began taking these skills that we were learning about ASOs and thinking about how we could apply them to this situation, Yu said.

Their early progress was aided by a $250,000 grant from the Quadrangle Fund for Advancing and Seeding Translational Research at HMS.

Over the past few years, the researchers developed several ASOs that seem promising.

These molecules dont bind to RNA transcribed from the mutated copy of the GRN gene that interferes with progranulin production. Instead, they attach to RNA made from the remaining healthy copy of the gene and by doing so, correct a natural inefficiency in progranulin processing.

Our strategy is to boost progranulin output from the normal copy of the gene, to make up for the lack of progranulin produced by the mutated copy, Huang said.

This strategy is particularly appealing, Yu added, because it means that the ASO does not need to be tailored to each patients specific mutation, as was the case for milasen, which was designed to target a mutation present in a single patient.

In human cells, the ASOs designed by the team have successfully increased progranulin expression.

Testing in mice would typically be the next step, but mice dont have the genetic sequences targeted by the molecules. Instead, the researchers moved to nonhuman primates, which have the same natural inefficiency in progranulin processing as humans.

We felt confident enough with our initial analysis that we thought we should try these ASOs in primates, Park said.

Bolstered by $1 million in funding from a 2020 Blavatnik Therapeutics Challenge Award, a primate study is ongoing.

So far, one ASO has been tested in one animal at different timepoints and doses. The molecule does not seem to be toxic and appears to alter the GRN gene as expected.

There are also signs that the ASO increases progranulin production in the brain, although the researchers are working on developing better ways to measure protein levels.

The molecule needs to be tested in more primates, the researchers cautioned, and they also plan to test the other ASOs they designed, but the results so far seem promising.

The ASO seems to work as well in a primate as was demonstrated in human cell lines, Yu said. This gets you pretty far along the path of what it takes to move something towards the clinic.

If the primate study continues to yield the desired outcomes, the researchers plan to move on to testing the ASO in clinical trials with humans.

The ASO would not only need to alter the GRN gene and increase progranulin levels, but, most importantly, to have a functional effect on patients with FTD.

The ultimate yardstick of success, Yu said, would be demonstrable slowing of disease progression.

Most likely, a treatment like this would be a potential way to keep the disease from progressing further, Yu said.

The chance to work on a therapy has been especially rewarding for Park, who typically spends his time on the computational side of things, far removed from the clinic.

We always consider how the algorithms that we develop might have some tangible impact, and this is a situation where we went from looking at genomic data to identifying the molecule and doing primate experiments in a very short time, Park said.

We typically think of a pharmaceutical company spending many years to develop a drug, but here, a single brilliant postdoctoral fellow at a computer used publicly available data to come up with a promising drug candidate in only a few weeks.

The researchers remain excited about the ASOs they designed, both for their potential to become drugs for FTD, as well as for their contribution to a growing class of novel therapies. The ASOs will continue to be developed by a company set to launch later this year.

ASOs offer several advantages as therapies, Park said. They can be injected directly into the spine, which allows them to easily enter the brain without having to traverse the near-impenetrable bloodbrain barrier that prevents so many medications from reaching their targets in the brain.

Also, unlike the gene-editing tool CRISPR, ASOs dont permanently alter a patients DNA, which means doses can be adjusted to a patients changing needs over time.

Park noted that the GRN gene their ASOs target may also play a role in neurodegenerative diseases beyond FTD, including amyotrophic lateral sclerosis (ALS) and Alzheimer's.

Moreover, it may be possible to develop similar ASOs for neurodegenerative diseases or developmental conditions driven by other mutations that affect only a single gene copy.

The question is whether you can pull this molecular trick for other neurologic gene targets, Yu said. One of the broader avenues for future research is exploring if this strategy can be recycled and applied to other conditions.

The speed at which the project progressed was largely a result of a collaboration across multiple labs and areas of expertise. For Yu it also highlights the promise of gene-targeting treatments.

Taking an idea and advancing it this far this quickly really does point out how promising this technology is. Our ASO is not a clinical drug yet there are a lot more steps but we showed that the concept and the strategy are robust, Yu said.

The story is as much about this process for making these genetically targeted therapies as it is about this particular ASO for this particular disease.

And while the story is far from over, the researchers hope that what started as an idea and a fortuitously timed collaboration will, in the end, be life-changing for patients.

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Collaboration Propels Research on Untreatable Neurodegenerative ... - Harvard Medical School