Nature calms me and nourishes my soul amid the challenges of giving care to my husband, Todd, who has ALS.

A few days ago, I walked down our country road, listening to singing birds and taking in spring’s beauty. I admired signs of new life — budding green leaves on trees, violets growing with new grass in ditches, and wild strawberry flowers in patches here and there. I look forward to retracing my steps in a month to eat the fruit.

On the way back, I stopped to inspect a marvelous scene of textures and contrast in a cluster of dead paper birch, jutting up into a deep blue sky. The trees had died long ago. The branches were bare, and the trunks had begun to rot. On one of the trees, three large mushrooms clung to the white bark.

Decaying birch trees. (Photo by Kristin Neva)

I walked to the base of the broken trees to take a closer look at the mushrooms. They were pretty from a distance, but looked dirty and pocked upon closer inspection.

Mushrooms such as these may not be beautiful, but they’re valuable to our world. Fungi feed on the moist deadwood, contributing to our ecosystem and recycling nutrients back into soil.

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A lesson for living with difficulty

At a distance, our life with ALS might look beautiful, even as the disease gradually took my husband’s mobility and is now taking his breathing. But the smiling pictures we put forward on social media and on our Christmas card don’t show the difficulties of the disease.

Up close, ALS is not pretty. Todd feels discomfort from his immobilization. He panics when he struggles to breathe or cough, and especially when he cannot communicate. We both feel weariness and isolation after years of ongoing decline.

I wouldn’t choose to live with these challenges. I’d rather have lived a life with new green leaves and flowers, but the spring of our marriage too quickly turned into living through the dying process. It’s hard to come to terms with the suffering that this disease has brought into our lives. It’s hard to come to terms with the suffering in the world.

But in a world where we love and are loved, my hope is that the pain of this life will be recycled into more compassion. We all have deadwood in our lives, but maybe with time the spores will work their magic, and something beautiful will grow out of nutrient-rich soil.

Note: ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of ALS News Today or its parent company, BioNews, and are intended to spark discussion about issues pertaining to ALS.

The post Lessons for living with ALS from my recent nature walk appeared first on ALS News Today.

People with amyotrophic lateral sclerosis (ALS) who continued treatment with NurOwn (debamestrocel) after completing a Phase 3 trial experienced additional benefits with extended treatment, data show.

The findings come from 10 adults who received up to six additional doses of NurOwn over nearly one year in an expanded access program (EAP). The patients experienced even greater reductions in neurofilament light chain (NfL) levels, a biomarker of nerve cell damage, after receiving these additional rounds of treatment.

An EAP, also known as a compassionate use program, allows patients with a serious or immediately life-threatening disease to gain access to an investigational treatment outside of clinical studies, when no comparable or satisfactory alternative options are available. 

Stacy Lindborg, PhD, shared these data at this year’s ALS Drug Development Summit, held May 21 to 23 in Boston. Her presentation was titled “Promising Longer-Term Biomarker Data from NurOwn Program in ALS: Spotlight on NfL in EAP Extension Cohort.”

“We are very pleased to share these important outcome data from the NurOwn EAP with the ALS community,” Lindborg, a member of the board of directors at BrainStorm Cell Therapeutics, which is developing NurOwn, said in a press release. She previously served as the company’s co-CEO.

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Phase 3b study to validate efficacy of NurOwn for mild to moderate ALS

With the go-ahead from the U.S. Food and Drug Administration, the company is planning to launch a Phase 3b study later this year to validate the efficacy of NurOwn in adults with mild to moderate ALS and gather enough data to support an application toward its potential approval.

The two-part study plans to enroll 200 patients who have been experiencing symptoms for less than two years. First, they will be randomly assigned to receive either NurOwn or a placebo for six months along with standard of care. Then, for the next six months, all will receive NurOwn.

To prepare NurOwn, a patient’s blood stem cells are collected and modified in the lab to release neurotrophic factors, or molecules that help nerve cells survive and thrive.

After being grown to hundreds of millions in number, the stem cells are injected into the patient’s spinal canal (intrathecal injection), where they are expected to release enough neurotrophic factors to ease inflammation and prevent nerve cells from dying, thereby slowing disease progression.

The earlier Phase 3 study (NCT03280056), which enrolled 189 adults with rapidly progressing ALS, failed to meet its main goal of slowing disease progression. However, an analysis of a small group of patients who started treatment with less advanced disease showed NurOwn may offer benefits over a placebo.

Eligible ALS participants who received all three intrathecal injections in the Phase 3 trial, including some who had been assigned to a placebo, could then enter an EAP (NCT04681118) and continue receiving NurOwn over two 28-week (six-month) periods.

A total of 10 patients entered the EAP. Eight completed the first period, where they received three doses, and six completed both periods, receiving a total of six doses.

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NurOwn significantly lowered levels of NfL in spinal fluid during Phase 3 trial

During the Phase 3 trial, treatment with NurOwn significantly lowered the levels of NfL in the spinal fluid compared with a placebo (by 11% vs. 1.6%), suggesting slower disease progression.

Changes in NfL may predict clinical outcomes, and “the data demonstrate a consistent reduction of neurofilament light (NfL) from baseline [the study’s start] among participants who were randomized to receive NurOwn in the Phase 3 study,” Lindborg said.

Among patients who entered the EAP, NurOwn treatment resulted in a 4% reduction in NfL levels over the Phase 3 trial. However, these patients showed further reductions in NfL levels during the EAP — by 27% after the first period and by 36% after the second period.

On the other hand, patients in the EAP who had initially received a placebo in the Phase 3 study had shown a 37% increase in the NfL levels during the trial. After receiving three doses of NurOwn as part of the EAP, their levels of NfL were 17% higher compared with baseline, and after six doses, they had decreased by 5%.

“These results suggest continual benefit from extended treatment of NurOwn,” the company wrote.

Lindborg said, “We look forward to confirming this finding in the planned Phase 3b study.”

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By taking advantage of a molecular interaction between the disease-related protein TDP-43 and another, innocuous protein, scientists have found a novel strategy that potentially may be used as a treatment for amyotrophic lateral sclerosis (ALS).

“Importantly, this interaction could be key to unlocking a treatment not just for ALS but also for other related neurological conditions, like frontotemporal dementia. … It is a gamechanger,” Michael Strong, MD, a physician-scientist at Western University, in Canada, said in a university press release.

The team detailed their findings in a manuscript titled “Mitigation of TDP-43 toxic phenotype by an RGNEF fragment in amyotrophic lateral sclerosis models,” published in the journal Brain.

According to the researchers, “it seems we are on the edge of a new era for the developing of treatments for neurodegenerative diseases such as ALS.”

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Scientists say TDP-43 protein interactions could be ‘key’ in treatment of ALS

Although the causes of ALS are not fully understood, the TDP-43 protein is thought to play a central role. In virtually all ALS cases, TDP-43 forms toxic clumps inside of nerve cells, which damage nerves and are thought to drive disease progression. Toxic clumps of TDP-43 also are characteristic of the related neurological disorder frontotemporal dementia.

In previous studies, Strong and colleagues at Western’s Schulich School of Medicine and Dentistry, and other institutions, had found that the TDP-43 protein is able to stick to another protein called RGNEF.

Now, the researchers conducted a detailed battery of molecular experiments in which they zeroed in on exactly how these two proteins stick together. They found that TDP-43 specifically can bind to a terminal section of RGNEF dubbed NF242.

NF242 is especially good at interacting with the disease-associated version of TDP-43 that characterizes ALS, the researchers found. In theory, this could mean that NF242 could be a useful treatment strategy for ALS, the basic idea being that NF242 could bind to TDP-43 and prevent it from forming toxic disease-driving clumps.

“Blocking toxic aggregates with an innocuous protein … could be as beneficial as eliminating the aggregates,” the researchers wrote.

To put this idea to the test, the researchers conducted experiments in fly and mouse models of ALS. In both animal models, inducing the production of NF242 led to less TDP-43 clumping as expected — and, as a result, the animals lived longer and had significantly better motor function.

Altogether, this study “suggests that a therapeutic strategy expressing NF242 or a biologically active fragment of NF242 could be promising in humans” with ALS and other disorders mediated by toxic TDP-43, the researchers concluded. However, they stressed that further work is needed to bring this approach toward clinical testing.

Blocking toxic aggregates [protein clumps] with an innocuous protein … could be as beneficial as eliminating the aggregates.

Strong and colleagues have set a goal of bringing this strategy into clinical trials in five years. To help support that goal, the Temerty Foundation, a Canada nonprofit, is donating $10 million CAD (about $7.3 million) over the next five years.

“Finding an effective treatment for ALS would mean so much to people living with this terrible disease and to their loved ones,” said James Temerty, founder of the foundation, who added that “Western is pushing the frontiers of ALS knowledge, and we are excited for the opportunity to contribute to the next phase of this groundbreaking research.”

According to Western, this donation brings to $18 million the Temerty Foundation’s total investment in neurodegenerative disease research at the university.

“Dr. Strong’s relentless dedication to his field is matched only by the Temerty family’s deep desire to make a difference for the thousands of people around the world diagnosed with this devastating disease,” said Alan Shepard, president of Western University.

“The investment — and foresight — of the Temerty Foundation has accelerated progress in finding an effective treatment for ALS. We are grateful for the Temerty family’s commitment to life-changing research,” Shepard added.

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An old adage says, “Do something today that your future self will thank you for.” Well, I’m in that future now, so today, I’m sending my past self a basket full of thanks. Why? Because every time I walk into our bathroom, I’m grateful. And I believe the modifications my husband and I made to our bathroom during my first year with ALS were among our best decisions.

Ask a real estate professional what the most important room in a house is and they’ll probably say the kitchen or the living room. But ask someone like me who lives with ALS and we’ll likely tell you it’s the bathroom. Among the many challenges of living with ALS are the physical symptoms of muscle stiffness and weakness. I have both and need to use a wheeled walker to steady my balance. That makes having to deal with awkwardly placed bathroom fixtures, along with tight spaces, a mighty frustrating experience.

Did you know that 80% of falls in the home happen in the bathroom? When I learned of that alarming statistic, I knew my ALS puts me in the high-risk category. So, besides making our bathroom a more pleasant experience and convenient for me, safety also became a high priority.

Following is a quick summary of the modifications we made:

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A sprinkling of grab bars

Standing in the middle of our bathroom, I asked myself, “If I felt off-balance, where should a grab bar be at the ready to steady me?” Soon, several strategically placed grab bars adorned the walls. Some were horizontal, others vertical, and one near the toilet was even at an angle. My advice is to be generous in the number of bars you install and run through all of your possible movements to choose the perfect placement.

A shower conversion

Originally, our bathroom had a walk-in shower with a glass door that swung open. Our remodeling began by pulling out the prefab shower and adding tile to the back walls and floor. This opened the entrance and eliminated the door and its bottom rim, which I had difficultly stepping over.

Instead of a door, we now have a simple pull-curtain. Other changes included a wall-mounted, hand-held shower head, a recessed area for soap and shampoo bottles, and of course, sturdy grab bars.

We also switched out our standard toilet for an ADA-height bidet model and made sure there was plenty of room to maneuver a rollator to access it.

A renovated bathroom helps keep columnist Dagmar Munn safe while living with ALS. (Photo by Dagmar Munn)

To chair or not to chair?

My husband and I discussed adding a shower chair, but I was resistant to using one. Sure, I had all the excuses: I didn’t need one yet, getting one meant I was giving up, and shower chairs are for old people anyway!

All it took was one instance of me having to shampoo my hair one-handed while my other hand clung to a grab bar and then the scary moment of feeling my bare feet sliding away on the soapy tiles below. That quickly changed my mind, and we promptly ordered a sturdy PVC shower chair.

I discovered that sitting while showering not only gave me full use of both my hands, but also my body felt relaxed and the chair gave me the luxury of time to enjoy taking a shower. Most importantly, I felt safe.

Final thoughts

At the time we began making the modifications to our bathroom, I wondered if it would be worth the expense. Now, 14 years later, I am thankful we did it.

It’s important to adapt my examples and experiences to what is best for you. Your doctor, caregivers, and family are good resources, as is Your ALS Guide, which offers many more helpful suggestions.

I believe we can live well while living with ALS.

Note: ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of ALS News Today or its parent company, BioNews, and are intended to spark discussion about issues pertaining to ALS.

The post These bathroom safety modifications were a great decision appeared first on ALS News Today.

NeuroSense Therapeutics is collaborating with PhaseV for insights into how to better design the protocol for the planned Phase 3 trial that will test PrimeC for amyotrophic lateral sclerosis (ALS).

A specialist in machine learning technology for clinical trials, PhaseV used data from the ongoing Phase 2b PARADIGM trial (NCT05357950) as input to a causal machine learning model. This is a form of artificial intelligence that can help unlock insights and identify features that may contribute to a treatment response.

As part of its independent analysis, the company found that PrimeC could work well in multiple subgroups of patients in the Phase 3 study, which should start in the coming months.

Being able to predict treatment outcomes in certain patients may help optimize the design of the upcoming trial by selecting the patients most likely to respond, while reducing costs.

ALS is a complex disease that manifests in unique ways in each patient. “Although there is an improved understanding of the underlying mechanisms of ALS, therapeutic options remain limited,” Raviv Pryluk, CEO and co-founder of PhaseV, said in a press release.

NeuroSense plans to submit an end-of-Phase 2 package for review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency, the FDA’s European counterpart, and discuss the clinical protocol for the Phase 3 trial with the regulators.

“There remains a critical need for new innovative approaches to address this devastating neurodegenerative disease,” said Alon Ben-Noon, CEO of NeuroSense. “We plan to continue to collaborate with PhaseV as we develop our Phase 3 trial.”

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Testing PrimeC in ALS

PrimeC contains fixed doses of two FDA-approved oral medications: the antibiotic ciprofloxacin and celecoxib, a pain killer that reduces inflammation. Both are expected to work together to slow or stop disease progression by blocking key mechanisms that lead up to ALS, such as inflammation, iron accumulation, and RNA processing.

PARADIGM is testing a long-acting formulation of PrimeC in 68 adults with ALS who started to see symptoms up to 2.5 years before enrolling. While continuing their standard ALS treatments, the participants were randomly assigned to PrimeC or a placebo, taken as two tablets twice daily for six months.

An analysis of PARADIGM’s per-protocol population — 62 adults with ALS who adhered well to the clinical protocol  — showed a significant 37.4% reduction in functional decline, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).

A subgroup of those patients who were at a higher risk for rapid disease progression had the most clinical benefit, with those treated with PrimeC for six months showing a significant, 43% reduction in functional decline over a placebo. High-risk patients made up about half the adults in the Phase 2b trial.

Another subgroup of newly diagnosed patients who’d had their first symptoms of ALS within a year of enrollment showed a 52% reduction in the rate of disease progression. This translated to a 7.76-point difference in favor of PrimeC on a maximum total of 48 points in the ALSFRS-R.

“Through our initial collaboration with PhaseV, we gained an even greater understanding of the effect of PrimeC across multiple patient subgroups,” Ben-Noon said. “We will apply these insights to optimize the design of our Phase 3 study with the aim of maximizing meaningful clinical results that will differentiate PrimeC in the market.”

“Through a unique combination of causal [machine learning], real-world data, and advanced statistical methods, we confirmed the potential clinical benefit of PrimeC,” Pryluk said. “Our analysis predicted a high rate of success for PrimeC in the Phase 3 clinical trial for multiple recommended subgroups.”

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Biogen and Ionis Pharmaceuticals have decided to terminate the development of BIIB105, their experimental treatment for amyotrophic lateral sclerosis (ALS), based on data from a Phase 1/2 clinical trial.

The therapy resulted in no significant clinical benefit compared with a placebo after six months, and data from the open-label extension part of the trial, which evaluated BIIB105 for about nine months, also showed no evidence of an impact on clinical outcome measures, according to a press release issued by the two companies.

Further, among trial participants, more adverse events were seen with the treatment for ALS than with the placebo, the release stated.

Analyses of trial data — to further understand underlying disease processes and the effects of BIIB105 in ALS — are ongoing and will be presented next month at the upcoming European Network to Cure ALS (ENCALS) meeting in Stockholm.

“We are deeply grateful for the contributions of the study participants and remain committed to developing treatments that can meaningfully change the disease trajectory for people living with ALS,” said Stephanie Fradette, head of Biogen’s neuromuscular development unit.

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ALSpire trial tested safety, tolerability of BIIB105

Several genetic mutations have been associated with an increased risk of developing ALS — including one alteration in the ATXN2 gene. Mutations in this gene involve an unusually higher repetition of a trio of nucleotides, or DNA building blocks, causing too many copies of an amino acid called glutamine to be inserted into the ataxin-2 protein.

Regardless of whether ATXN2 is mutated or not, studies have suggested that the ataxin-2 protein may be targeted to prevent the toxic accumulation of TDP-43 protein clumps — which is observed in nearly 97% of all ALS cases.

Preclinical data supports this, demonstrating that blocking ataxin-2 in a mouse model of TDP-43-related ALS led to slower disease progression and longer survival times.

BIIB105 is an antisense oligonucleotide, or ASO, designed to reduce the amount of ataxin-2 in cells by binding and promoting the degradation of its messenger RNA — the intermediate molecule derived from the gene that’s used to guide protein production.

The ALSpire Phase 1/2 clinical trial (NCT04494256) was launched in 2020 to investigate the safety and tolerability of BIIB105 in about 99 adults with ALS, with or without mutations in the ATXN2 gene.

In a first part, participants were randomly assigned to receive either BIIB105 or a placebo, administered directly into the spinal canal (intrathecal injection), for three to six months.

Then, those who completed the placebo-controlled period were eligible to enroll in the open-label extension, in which all would receive the treatment for ALS for as long as three years.

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Treatment candidate for ALS failed to slow disease progression

Results from the first part showed the therapy significantly reduced ataxin-2 levels in the spinal fluid, indicating it was working as intended.

However, no reductions in neurofilament light chain (NfL) levels, a marker of nerve damage, were observed, and BIIB105 also had no impact on measures of disability, breathing, and muscle strength over this period.

The most common side effects reported in people who received BIIB105 in this part included pain associated with the injection, headache, and fall. But according to the release, side effects or “[adverse events] leading to study discontinuation” occurred more frequently in the BIIB105 group (8.3%) than among those treated with the placebo (3.6%).

“While BIIB105 lowered ATXN2 protein, it did not reduce neurofilament, which gives us confidence that BIIB105 did not slow the disease process,” Fradette said.

Treatment over more than 40 weeks in the open-label extension part of the study led to similar results, with patients experiencing sustained reductions in ataxin-2 levels, but no significant changes in NfL or clinical measures of efficacy.

BIIB105 did not slow the disease process.

The absence of benefit was observed in all analyzed patient groups, including those with mutations in the ATXN2 gene.

The ongoing collaboration between the two companies has resulted in other ASO candidates for ALS, including the now-approved treatment Qalsody (tofersen) for people with SOD1 mutations. However, in 2022, the companies also discontinued development of another treatment candidate called BIIB078 for C9orf72-associated ALS, after a Phase 1 trial found no significant clinical benefit compared with a placebo. BIIB078 had been shown to be generally safe and well tolerated in that trial.

Ionis also is working on a similar therapy called ulefnersen, previously known as ION363, for people with mutations in the FUS gene.

“Ionis continues to be committed to the ALS community and is advancing our Phase 3 ulefnersen program for people with the genetic form of the disease known as FUS-ALS,” said Frank Bennett, PhD, Ionis’ executive vice president and chief scientific officer.

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A new amyotrophic lateral sclerosis (ALS) assessment called delta-FS — defined as the rate of decline over time in the ALS Functional Rating Scale-Revised (ALSFRS-R) — has been proposed as an attractive, easily obtainable tool to monitor disease severity and predict patient prognosis.

The assessment also could be used to identify certain groups of patients who could benefit the most from an experimental treatment, helping to optimize patient selection in clinical trials, the researchers said.

“[Delta]-FS is a clinically relevant, independent predictor of survival, capable of distinguishing patient subgroups that have a different course of disease progression,” Albert Ludolph, MD, PhD, a professor at the University Hospital and Medical Faculty of Ulm, in Germany, and the study’s senior author, said in a press release.

“Categorization of the ALS population via post-onset [delta]-FS is therefore an important study design consideration that may facilitate optimization of drug effectiveness and patient management, and as such is recommended for inclusion in the design of clinical trials,” Ludolph said.

The merits of delta-FS was discussed by researchers in the study “Categorization of the amyotrophic lateral sclerosis population via the clinical determinant of post-onset ΔFS for study design and medical practice,” which was published in the journal Muscle & Nerve.

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Seeking new, more nuanced measures of disease severity in ALS

Early symptoms of ALS can vary substantially from person to person. Most patients first experience weakness in their limb muscles (known as limb-onset ALS), while others have such symptoms in the muscles around the face and throat (bulbar-onset disease). Over time, muscle weakness often develops into paralysis and breathing difficulties, with many patients dying of respiratory failure.

As ALS is a progressive disease, its symptoms are known to worsen over time. However, the rate of decline to eventual death can vary between patients, from a matter of months to more than a decade.

The most widely used measure of ALS severity in clinical practice and clinical trials is the ALS Functional Rating Scale-Revised, known more simply as ALSFRS-R. But despite its widespread acceptance, ALSFRS-R has certain limitations, including its inability to distinguish between patients with very severe or very mild disability and the absence of a cognitive function domain, or area of assessment.

ALSFRS-R also doesn’t capture non-linear decline, or periods of rapid or slow decline that may sometimes occur over time.

Now, researchers in Germany, France, and the U.S. are proposing delta-FS, defined by the rate of decline in ALSFRS-R scores, as a new measure of disease severity in ALS.

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Delta-FS has been shown to be a sensitive and independent clinical outcome measure. This makes it a predictor of survival and capable of distinguishing patient subgroups with different disease courses.

“In this article we discuss the merits of post-onset [delta]-FS as a tool for innovative ALS study design,” Ludolph said.

To capture the non-linear features of ALS, delta-FS values can be calculated differently at each stage of the disease, the researchers noted. Early, or post-onset delta-FS measures the initial ALSFRS-R rate of decline from symptom onset, while late, or interval delta-FS considers the decline between follow-up assessments.

Another distinguishing feature is the timeframe differences in calculating delta-FS. Post-onset delta-FS is measured about 11 to 24 months after symptom onset, so it is less affected by short-term variations in ALSFRS-R scores. Moreover, post-onset delta-FS can be measured as part of routine clinical practice, providing physicians who treat ALS with a patient selection tool.

According to the researchers, post-onset delta-FS can be used to classify and select participants in clinical trials, providing more homogeneous patient populations. It also allows for subgroup analysis based on variations in ALS severity, which may detect differences in treatment response, as well as underlying disease-related processes, across the overall ALS population.

The team noted two limitations of post-onset delta-FS. First, it is a retrospective measure, meaning it collects data from the past. Second, as a subjective assessment of functional disability, regular training of assessors is required to ensure reliability, the team stressed.

To date, several clinical trials have applied delta-FS in patient selection. One is AB10015 (NCT02588677), a Phase 2/3 study that evaluated AB Science’s masitinib, an add-on oral medication meant to slow ALS progression.

“Although this article is not specifically directed towards the masitinib study AB10015 in ALS, it describes very well the design philosophy behind that study and as such is a strong validation of this approach,” said Olivier Hermine, MD, PhD, president of the scientific committee of AB Science.

There are no insurmountable barriers regarding the application of post-onset [delta]-FS in clinical practice, making it [a] very attractive enrichment tool that is, can and should be regularly incorporated into ALS trial design.

The researchers suggested that delta-FS be put into use as soon as possible as a measure of disease severity.

“Overall, there are no insurmountable barriers regarding the application of post-onset [delta]-FS in clinical practice, making it [a] very attractive enrichment tool that is, can and should be regularly incorporated into ALS trial design,” the researchers concluded.

Hermine added that this study, sponsored by AB, “shows that there is consensus among … key opinion leaders that post-onset [delta]-FS is a simple-to-use instrument for patient selection, with no obvious barriers regarding its application in clinical practice.”

The post Scientists propose delta-FS as new measure of disease severity in ALS appeared first on ALS News Today.

My son joined middle school track this year, and after a few days of practice, my husband, Todd, asked how it was going.

“I’m not a long-distance runner,” he said. “I don’t know how to pace myself.”

“I was no good for any distance, either,” Todd said. “I ran the 200- and 400-meter dashes.”

“You were in track?” my son asked incredulously. We’ve both heard Todd talk about high school wrestling, but neither of us have heard him mention that he was in track.

Yesterday was my son’s first track meet. He competed in the 200-meter hurdles event, which had two heats of runners. My son was in a heat with only two other boys — one of his buddies and a kid from another school. He and his buddy sprinted ahead of the other runner and were neck and neck for the first 100 meters, my son just slightly ahead. His friend pushed forward, and my son glanced sideways at him. With a burst of speed, my son pulled ahead, winning his heat and ultimately the event.

My son said he’d never run that hard before.

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A hard race

ALS is a sprint for some and a long-distance race for others, but we don’t entirely know which it is when it begins.

Sometimes people new to the disease ask, “Should we spend money on renovating our home so we have an accessible bathroom, or should we travel?”

It depends.

When Todd was diagnosed with ALS, his neurologist told him, “Progression is typically linear. If it starts slow, it will continue slow.” Based on Todd’s self-assessment of his strength a year prior, he thought he may be on the upper end of the bell curve relative to the estimated two-to-five-year life expectancy after symptom onset. We put our house on the market and made plans to build a one-story house with wide doorways and an accessible bathroom.

A year later, one of our neighbors also was diagnosed with ALS. In his case, the disease was progressing quickly, and he and his wife chose to travel to Europe to meet her family. He left walking and returned in a wheelchair. A mobility store loaned him a used scooter, and volunteers built a ramp into his house. There was no time for him and his wife to even consider home renovations. He died a year later.

Todd was in a power wheelchair by his fourth year of ALS, but he was still breathing well enough, and we thought he probably had a few active years left. We made a similar calculation with our decision to purchase an accessible vehicle. It was convenient and improved his quality of life, but at this point, if the van dies, it would make more sense to use a transport service on the rare occasions he needs to see a doctor, as he only leaves our home for medical appointments now.

After five years with the disease, we realized we were in a long-distance race, and I would need to pace myself with caregiving, particularly at night. Todd wasn’t able to sleep independently, and I wasn’t able to go without uninterrupted sleep for long. I did it for months, but when that turned into a year and then two, it became unsustainable. We eventually started hiring nighttime help. On nights when we don’t have a caregiver, Todd stays up on his computer and in his wheelchair, where he is more independent and can adjust his seat to stay comfortable. I get a few hours of sleep and then get up to put him into bed.

I’ve also had to pace myself with other demands of caregiving. I’ve learned not to immediately switch gears every time he asks for something. If Todd asks me to do something that isn’t urgent, I might choose to finish whatever I’m in the middle of first, such as loading the dishwasher.

Todd sometimes calls me with panic in his voice, either to use the bathroom or to cough. In those moments, I move swiftly, but I’ve learned to stay calm and work methodically, detached from the stress of the situation so I can do what needs to be done.

ALS is a hard race, whether it’s a sprint in which we run harder than we’ve ever run before or a marathon where we try to pace ourselves to go the distance.

Note: ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of ALS News Today or its parent company, BioNews, and are intended to spark discussion about issues pertaining to ALS.

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Target ALS has reached its capital campaign goal of $250 million to accelerate research and fuel scientific breakthroughs in amyotrophic lateral sclerosis (ALS).

The campaign was spearheaded by founder Dan Doctoroff, a former deputy New York City mayor who was diagnosed with ALS in late 2021. He was committed to raising the funds to increase investment in ALS by leveraging his deep relationships and fundraising talents.

“This is deeply personal for me given my family history; my dad and my uncle died from ALS, but my mission is to save the one in 400 people who will die of this disease,” Doctoroff said in a Target ALS press release. “Over the past 11 years, we have developed a unique collaborative model to advance ALS research, and the $250 million – and I’m not stopping until I can’t do it anymore – will advance discovery dramatically.”

Doctoroff and his team at Target ALS, a 501(c)(3) medical research foundation, set out to raise awareness and funds for ALS research and put together a comprehensive ALS research investment strategy with the help of specialists in ALS and other neurodegenerative diseases, along with those who’ve been affected by the disease. The strategy also incorporates the latest in scientific research and drug discovery.

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7 Pillars of research success

Over the next eight years, the $250 million will be invested across Target ALS’ Seven Pillars to fuel scientific breakthroughs and drive the development of biomarkers and ALS therapies.

In Pillar 1, called Diversification and Expansion of Talent, fresh perspectives and new technologies will be attracted to advance ALS research led by the next generation of researchers and clinicians. Through grant-making programs, Target ALS will support researchers at different stages of their careers to encourage long-term interest in ALS.

In Pillar 2, called Maintenance and Expansion of Scientific Core Facilities, ALS research  will be democratize by granting swift, unrestricted access to biosamples, datasets, and reagents for scientists worldwide. So far, more than 1,100 ALS projects have used these resources.

In Pillar 3, called Applying the Target ALS Model to Related Diseases, the focus will be placed on related diseases with shared genetic roots and underlying disease mechanisms, such as frontotemporal dementia and Alzheimer’s disease, to broaden the field of experts working on ALS and find new research paths.

In Pillar 4, called Discovery and Development of New Therapeutic Targets, collaborations will be fostered between academic scientists specializing in disease biology and industry partners with expertise in drug discovery. The goal is to expand the pipeline of potential therapies and speed their path toward clinical application.

In Pillar 5, called Discovery and Development of Toolkit of Biomarkers, new biomarkers will be found to aid in shortening the time to diagnosis, monitoring disease progression, and assessing treatment efficacy with accurate biomarkers, which will also improve the efficiency of clinical trials.

In Pillar 6, called Treatment of Ultra-Rare Forms of ALS, the focus will be on investigating ultra-rare ALS variants to uncover unique disease-related targets toward broader applications in ALS and other diseases.

In Pillar 7, called Prudent Growth of Target ALS Capacity, the aim will be to expand Target ALS’ team and leadership to strengthen its expertise across different fields and increase its capacity for further work supporting ALS research.

“The true achievement is not the fundraising itself, but what we will be able to accomplish with the resources entrusted to us,” said Manish Raisinghani, PhD, president and CEO of Target ALS. “We take this opportunity as a responsibility to help build a world where everyone with ALS lives, and we won’t stop until we realize this vision.”

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Scientists at Broken String Biosciences and the Francis Crick Institute are teaming up to study how genomic instability, or an increased tendency to DNA mutations, contributes to amyotrophic lateral sclerosis (ALS).

The findings may shed light on the mechanisms leading to sporadic cases of ALS, the term used for cases in those with no known family history of the disease, and potentially help to devise new approaches for improved diagnosis and treatment of ALS patients.

The researchers will use Broken String’s INDUCE-seq technology to identify breaks in DNA in order to track genomic instability and better understand its role in disease.

“This collaboration with the Crick Institute is validation of our differentiated approach to DNA break-mapping,” Felix Dobbs. PhD, CEO of Broken String, said in a press release announcing the collaboration.

The project is “a fantastic opportunity to apply our expertise across other key research areas to support the advancement of human health,” Dobbs said. “There is an unmet clinical need for effective ALS treatments, as well as strategies for earlier diagnosis that can significantly improve patient outcomes.”

DNA provides cells with the instructions for making all their proteins, and the genetic code stored in DNA is vital for cellular function. Cells have molecular mechanisms to repair damaged DNA, but they aren’t perfect, and the process can result in small changes and mutations in the genetic code. Genomic instability refers to a higher than normal frequency of mutations in certain cells due to defects in the repair machinery.

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Exploring how failures in cell repair lead to ALS

Simon Boulton, PhD, principal group leader and assistant research director at the institute, said the research is “focused on exploring how cells repair damage to their DNA, and how failures in this process lead to disease.”

“We are excited to leverage the INDUCE-seq platform’s unique capabilities in directly measuring and quantifying DNA double-strand breaks, and applying this to deepen our understanding of diseases that have genomic instability as a contributing factor, such as ALS,” Boulton said.

Joining Boulton on the project is Crick researcher Nishita Parnandi, PhD, who like Boulton is an expert on DNA damage. Crick researchers who focus on ALS, including senior group leader Rickie Patani, PhD, and visiting scientist Giulia Tyzack, PhD, also will be involved, as will Simon Reed, PhD, co-founder and CSO at Broken String.

“Following exploratory work with Professor Reed, we were keen to collaborate with Broken String,” Boulton said.

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