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A partnership between <a href="https://www.lifearc.org/">LifeArc</a> and the UK Dementia Research Institute (UK DRI) is awarding £14.5 million (about $18.2 million) to seven research projects aimed at developing new tests, treatments, and devices for neurodegenerative diseases.
“Our partnership with UK DRI allows us to identify and back the most promising translational research with the potential to transform the lives of those with neurodegenerative conditions,” Karen Skinner, LifeArc’s chief project and portfolio officer, said in an <a href="https://www.globenewswire.com/news-release/2023/11/14/2779633/0/en/MULTI-MILLION-POUND-BOOST-FOR-RESEARCH-PROJECTS-AIMED-AT-DEVELOPING-NEW-TESTS-TREATMENTS-AND-DEVICES-FOR-NEURODEGENERATIVE-DISEASES.html">organization press release</a>.
More than 1 million people in the U.K. live with conditions such as <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), frontotemporal dementia (FTD), <a href="https://alzheimersnewstoday.com/what-is-alzheimers-disease/">Alzheimer’s</a>, and <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson’s disease</a>.
The selected projects are the first to be funded through the £30 million strategic partnership, which was established in 2022 to leverage UK DRI’s research skills and LifeArc’s translational competencies to advance research in dementia and contribute to bringing laboratory discoveries closer to clinical applications, thereby speeding up the development of new therapies.
“By working together, we reduce risk by further validating opportunities and enhancing appeal to potential future partners, such as pharmaceutical companies, who can subsequently advance these innovations through the clinic and onto the market for those who desperately need them,” Skinner said.
[recommended-reading id=87476]
<h3>7 projects for ALS, neurodegenerative disease research</h3>
ALS is marked by damage to motor neurons, the nerve cells that control voluntary movements. This results in trouble controlling muscles, leading to <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a> such as trouble walking, swallowing, speaking, and breathing.
Patients can also experience mental health, cognitive, and behavioral problems. Up to 20% of people with ALS will develop dementia, which features marked changes in thinking and behavior that affect the ability to perform everyday tasks, increasing the burden for patients and their families.
Among the seven projects receiving funding, three will investigate new treatments for motor neuron diseases, a group that include ALS and feature damage to motor neurons.
One, led by Marc-David Ruepp, PhD, a group leader at the UK DRI center at King’s College London, will investigate a unique gene therapy approach for ALS and FTD, a related condition made up of a group of neurological disorders that affect brain regions typically associated with personality, behavior, and language.
A project led by Adrian Isaacs, PhD, a professor of neurodegenerative disease at UK DRI center at University College London, would develop a small molecular drug target for ALS and FTD.
And a study led by Siddharthan Chandran, PhD, UK DRI&#8217;s director and a researcher at the University of Edinburgh, will try to identify new combinations of existing medications to treat motor neuron disease.
Three projects will focus on Alzheimer&#8217;s and small vessel disease, and a fourth one hopes to improve care for people with dementia by harnessing digital and computational tools.
“It is fantastic to see such a breadth of high-quality translational research from across many of our [centers] in these projects. These pioneering projects will bring us ever closer to our mission of new treatments for people affected by dementia,” said Kay Penicud, UK DRI’s director of innovation and business.
Neurodegenerative diseases are one of five healthcare areas identified by LifeArc as having a significant unmet patient need. The U.K. medical research charity is investing up to £100m in research on neurodegenerative conditions. UK DRI is the largest single investment in dementia research, operating across seven leading U.K. universities. It works to prevent, treat, and care for people with all types of dementia.

£14.5M awarded toward ALS, other neurodegenerative disease projects

<a href="https://www.pasithea.com/">Pasithea Therapeutics</a> has selected a lead candidate for its PAS-003 program, which is intended to target a &#8220;velcro-like&#8221; protein to treat <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The new therapy is a humanized monoclonal antibody that potently inhibits the alpha-5/beta-1 integrin protein. It was selected after extensive screening and characterization studies deemed it the best candidate for both <a href="https://alsnewstoday.com/forms-of-als/sporadic-als/">sporadic</a> and <a href="https://alsnewstoday.com/forms-of-als/familial-als/">familial ALS</a>.
PAS-003 is ready for manufacturing and preclinical studies to support an investigational new drug (IND) application to request advancing it into clinical testing.
“We have chosen the most optimal [alpha-5/beta-1]] humanized [monoclonal antibody] for the treatment of both sporadic and familial ALS. PAS-003 is now ready for manufacturing and IND-enabling studies,&#8221; Tiago Reis Marques, CEO of Pasithea, said in a <a href="https://www.globenewswire.com/news-release/2023/11/09/2777261/0/en/Pasithea-Therapeutics-Selects-PAS-003-Lead-Development-Candidate-a-Humanized-Monoclonal-Antibody-that-Targets-%CE%B15%CE%B21-Integrin-for-the-Treatment-of-both-Sporadic-and-Familial-ALS.html">company press release</a>.
The PAS-003 program is being established after <a href="https://alsnewstoday.com/news/als-therapy-target-integrin-that-spurs-immune-cells-to-eat-neurons/">promising data from a recent study</a> in animal models of ALS. In a collaborative effort between Pasithea and researchers at Stanford, the Mayo Clinic, and Oregon Health &amp; Science University, the alpha-5/beta-1 integrin was identified as a possible target for easing nerve cell loss in ALS.
“I have spent my career studying integrins and I believe [alpha-5/beta-1] integrin is an important therapeutic target for the treatment of ALS,&#8221; said Lawrence Steinman, a neurologist and professor at Stanford Medical School, and co-lead author of the breakthrough study. &#8220;I am as excited about the PAS-003 development program as I was 30 years ago when I first published as senior author in Nature on targeting integrins for treating multiple sclerosis.&#8221;
Steinman is also co-founder and chairman of Pasithea.
[recommended-reading id=86261]
<h3>Integrin&#8217;s role in ALS disease progression</h3>
ALS is marked by the progressive damage and death of motor neurons, nerve cells that control voluntary muscle movement. As a result, patients develop a range of <a href="https://alsnewstoday.com/symptoms-of-als-2/">disease symptoms</a>, from trouble walking and speaking to difficulty swallowing and breathing.
While the processes underlying the onset and development of ALS aren&#8217;t fully understood, inflammation in the central nervous system, the brain and spinal cord, is believed to be significant.
In this study, scientists found alpha-5/beta-1 integrin levels were markedly high in microgila and macrophages, immune cells that work to engulf and destroy threats and are known to play a role in the <a href="https://alsnewstoday.com/stages-of-als/">progression of ALS</a>.
This was observed in animals with late-stage ALS, but not healthy mice, and in post-mortem samples from ALS patients. In patients, immune cells positive for the integrin were located close to motor neurons and in regions where motor neurons were previously found.
Treatment with an anti-alpha-5/beta-1 integrin antibody delayed disease progression in mice and extended survival. The animals also had better motor function, fewer symptoms, and better general health.
The findings highlighted the role of the alpha-5/beta-1 integrin “on different cell types involved in neuroinflammation in ALS and has shown that blocking α5β1 integrin is a therapeutic target for the treatment of ALS,” Marques said. “We are pleased to have achieved this significant development milestone through extensive and repeated preclinical studies, to have made key patent filings and we are looking forward to introducing our PAS-003 program to partners to appropriately advance this important program to the clinic.&#8221;
Pasithea’s development of its anti-integrin antibodies was supported by an <a href="https://alsnewstoday.com/news/pasithea-therapeutics-receives-au1-million-develop-antibodies-als/">award worth AU$1 million</a> (about $660,000) from <a href="https://fightmnd.org.au/">FightMND</a>, an Australian nonprofit that supports disease research.
“I would like to thank all of the parties involved, including the Mayo Clinic and Oregon Health Sciences University, who were influential in the discovery and research efforts, as well as Paul B. Manning and FightMND, a registered not-for-profit Australian charity, who helped fund the progress to our lead candidate selection,&#8221; Steinman said.

Lead PAS-003 candidate chosen to target key protein in ALS

<a href="https://insilicotrials.com">InSilicoTrials</a> and <a href="https://www.axoltis.com">Axoltis Pharma</a> are teaming up to advance the development of NX210c, the latter’s lead candidate for treating <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) and other neurodegenerative diseases.
Axoltis will use InSilicoTrials’ <a href="https://insilicotrials.com/platform2/">simulation platform</a> to see how well NX210c works in virtual simulations that mimic brain and spinal cord features of people with neurological conditions, including ALS, <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson’s disease</a>, and <a href="https://multiplesclerosisnewstoday.com/multiple-sclerosis-overview/">multiple sclerosis</a>.
“This partnership represents an exciting synergy between cutting-edge simulation technologies and innovative biotechnological advancements,” Luca Emili, CEO of InSilicoTrials, said in a <a href="https://www.prnewswire.co.uk/news-releases/insilicotrials-and-axoltis-pharma-collaborate-to-advance-therapeutic-solutions-for-neurological-disorders-301886792.html">company press release</a>. “Together, we aim to unlock new insights and develop groundbreaking treatments that will positively impact the lives of patients with neurologic impairments worldwide.&#8221;
InSilicoTrials’s platform combines artificial intelligence (AI) and software tools to develop potential treatments faster while cutting the costs associated with time-consuming and often expensive clinical trials.
It will assess the best dosing regimens of NX210c based on how it impacts brain health and the levels of certain biomarkers, and how safe and effective it might be in a wide range of neurological and neurodegenerative conditions.
“We are very delighted to initiate this collaboration with InSilicoTrials and have the opportunity to optimize and accelerate our next clinical steps,” Yann Godfrin, PhD, CEO of Axoltis, said. “Integrating their industry-leading AI and computational modeling solutions in the development plan of our promising disease-modifying drug will allow us to address the pressing challenges faced by individuals suffering from neurological disorders.&#8221;
[recommended-reading id=84680]
<h3>What is NX210c and how does it work?</h3>
A Phase 2 clinical trial of NX210c in people with ALS is <a href="https://www.axoltis.com/pipeline/">expected to start in the coming years</a>. Multiple, increasing doses of the therapy are being evaluated in healthy elderly people in a <a href="https://classic.clinicaltrials.gov/ct2/show/NCT05827653">Phase 1 trial (NCT05827653)</a>. That study is expected to enroll people with <a href="https://alzheimersnewstoday.com/what-is-alzheimers-disease/">Alzheimer’s disease</a>.
Several neurodegenerative diseases, including ALS, share features such as blood-brain barrier (BBB) leakage, neuronal communication problems, and neuron death. The blood-brain barrier is a highly selective membrane that prevents microbes and other harmful molecules in circulation from entering the brain and spinal cord.
In ALS, motor neurons — nerve cells that control voluntary movements — are affected, causing <a href="https://alsnewstoday.com/symptoms-of-als/">muscle weakness</a> and other symptoms.
NX210c is a lab-made small peptide (small protein) derived from SCO-spondin, a protein involved in several developmental processes, including neuronal survival, maturation, and growth. NX210c corresponds to the specific domain of SCO-spondin that mainly exerts its beneficial effects.
According to Axoltis, NX210c has <a href="https://www.axoltis.com/our-product/properties/">three main properties</a> that make it a promising candidate for treating neurodegenerative conditions: it&#8217;s neuroprotective, it boosts neuronal communication, and it improves the integrity of the blood-brain barrier.
It helps neurons in the brain <a href="https://www.mdpi.com/1422-0067/23/16/8867">communicate better</a> by increasing the transmission of glutamate signals, earlier work in lab-grown neurons and mice has shown. At the same time, it <a href="https://www.sciencedirect.com/science/article/pii/S0306452221000701">protects neurons</a> against damage caused by glutamate overload.
Glutamate is a chemical messenger molecule used by neurons to communicate with each other and plays a crucial role in learning, memory, and brain function. Glutamate signaling <a href="https://alsnewstoday.com/news/reduced-editing-efficiency-mrna-molecule-als-may-be-biomarker/">is abnormal in ALS</a>, suggesting a potential role in the disease.
By acting on the connections between BBB cells, NX210c is thought to help prevent leakage into the brain, including the entry of the <a href="https://alsnewstoday.com/causes-of-als/">overactive immune cells</a> known to contribute to neuroinflammation in ALS.
In a previous Phase 1 trial with 39 healthy people, the related peptide NX210 was found to be <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338184/">safe and well tolerated</a> when given as single ascending doses into the bloodstream. It also was rapidly eliminated from the bloodstream.
The therapy received orphan drug status in the U.S. for ALS and in Europe for treating spinal cord injury. The designation is meant to accelerate a therapy’s clinical development and regulatory review.

InSilicoTrials, Axoltis partner to work on potential ALS therapy

It&#8217;s long been known that some molecules are misplaced in the nerve cells that progressively die in <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), but a new study shows this affects hundreds of different molecules, not just a handful, as previously thought.
“This research represents a shift in our thinking about what causes ALS – it doesn’t involve abnormal movement of just a few proteins, but the abnormal localization of hundreds of proteins and mRNAs [messenger RNAs],” Rickie Patani, MD, PhD, the study’s senior author at the Francis Crick Institute, in London, U.K., said in an <a href="https://www.crick.ac.uk/news-and-reports/2023-07-21_research-reveals-the-scale-of-disorder-underpinning-motor-neurone-disease">institute press release</a>. “This opens new avenues for research and potential therapies.&#8221; mRNA is an intermediary molecule derived from DNA that guides protein production.
The researchers also found the experimental therapy ML240, which blocks the activity of the ALS-linked enzyme VCP, could partially block the misplacement of cellular contents in patient-derived nerve cells.
“As ML240 improved the mislocalization and other disease features in ALS, we now need to understand if this can be a tractable therapy for ALS more widely. This is just the beginning and there is lots more to do, but our work provides some hope for effective therapies,” Patani said.
The study may be an important first step, but the researchers emphasized more work is needed before the therapy can be given to people. It hasn&#8217;t yet been tested in animals, a crucial step for assessing the safety of investigational treatments.
The study, “<a href="https://www.sciencedirect.com/science/article/pii/S0896627323004786?via%3Dihub">Nucleocytoplasmic mRNA redistribution accompanies RNA binding protein mislocalization in ALS motor neurons and is restored by VCP ATPase inhibition</a>,” was published in <a href="https://www.sciencedirect.com/journal/neuron">Neuron</a>.
[recommended-reading id=85075]
<h3>Role of incorrect placement in motor neurons in ALS</h3>
ALS <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a> are driven by the death and dysfunction of motor neurons, the specialized nerve cells that control voluntary movement. While the <a href="https://alsnewstoday.com/causes-of-als/">causes</a> of their dysfunction are incompletely understood, incorrect placement of proteins and mRNA has long been thought to be involved.
Previous research has suggested that certain proteins normally found in the nucleus (the central cellular compartment that houses all genetic information) are instead found outside of it in ALS patients’ cells.
One such protein is TDP-43, which helps regulate RNA processing and forms toxic clumps outside the nucleus — a hallmark of the disease. While TDP-43 mislocalization has been <a href="https://alsnewstoday.com/news/scientists-find-how-tdp-43-affects-important-nerve-protein-als/">extensively documented</a>, it was assumed that ALS-associated mislocalization mainly impacted just a few key molecules.
In this study, the scientists performed wide-scale assessments of mRNA and protein localization in motor neurons from healthy people and ALS patients with mutations in either the TARDBP or VCP genes. TARDBP encodes for TDP-43, while VCP encodes an enzyme of the same name that&#8217;s involved in protein breakdown.
The researchers found that hundreds of mRNA molecules and proteins were abnormally distributed in patients’ cells. Molecules usually found in the nucleus were outside it, while molecules normally found outside the nucleus were inside.
The findings supported the presence of transport issues in the cells of people with ALS.
There were some differences in the specific molecules that were incorrectly located between cells carrying different ALS-associated mutations. There was still a lot of overlap, however, and several of the shared misplaced molecules have been implicated in developing ALS.
Across mutations, about two-thirds of the misplaced proteins moved from inside the nucleus to outside it. Analyses of cells from deceased patients showed similar findings.
“These findings indicate that ALS mutations induce notable changes in [the distribution of molecules inside and outside the nucleus], which is remarkably consistent across mutations,” the researchers wrote.
“We were surprised to see the extent of the mislocalization, particularly for mRNAs, as this hasn’t been reported before,” said Oliver Ziff, MD, PhD, one of the study’s co-first authors at the Crick.
Many of the mRNAs and proteins were able to physically stick to each other. The researchers speculated this could help explain why so many molecules become misplaced, since one moving molecule might drag along others that are attached to it.
“These data support the concept that interactions between mRNA and proteins contribute to widespread [inside and outside the nucleus] redistribution and mislocalization in ALS motor neurons,” the scientists wrote.
<h3>ML240 helps restore molecular localization</h3>
The researchers also showed that ML240, a VCP-blocking investigational therapy, restored the localization of more than 95% of these molecules in patients’ motor neurons, regardless of the mutated gene.
ML240 was found to change how the VCP protein interacts with other proteins that help control the movement of molecules into and out of the nucleus. This effect was seen only in cells with VCP mutations, not with TARDBP mutations.
Nonetheless, in motor neurons with either mutation, blocking the VCP protein with ML240 led to reductions in DNA damage and other signs of ALS-associated cellular damage.
While these findings are promising, the researchers emphasized the study was limited to cell models and only in those caused by a few ALS-associated mutations.
“Future research should aim to validate these findings in different ALS <a href="https://alsnewstoday.com/forms-of-als/">genetic backgrounds</a> and models,” they wrote, noting more studies into the underlying cause of improper molecule placement in ALS cells are needed.
“The goal now is to find where this problem starts and there are many intriguing possibilities, one being a breakdown in the transport between the nucleus and [outside the nucleus],” Ziff said.

In ALS, motor neurons’ molecule misplacement is widespread: Study

<a href="https://www.athira.com">Athira Pharma</a>’s experimental therapy ATH-1105 shows anti-inflammatory and neuroprotective effects, promoting neuron growth and reducing damage associated with mechanisms of <a href="https://alsnewstoday.com">amyotrophic lateral sclerosis</a> (ALS) and frontotemporal dementia (FTD), a related condition.
The small molecule reduced inflammation and the buildup of a faulty version of TDP-43, a protein that’s thought to drive neuronal damage in both ALS and FTD.
That’s according to new data from preclinical studies in lab-grown cells and a mouse model of the two diseases that were shared in a poster at this year’s Alzheimer’s Association International Conference (AAIC), July 16-20, virtually and in person in Amsterdam, the Netherlands.
The poster was titled “<a href="https://www.athira.com/wp-content/uploads/2023/07/AAIC2023_FTD_L5_6July2023.pdf">ATH-1105, a small-molecule positive modulator of the HGF/MET system, is neuroprotective and attenuates TDP-43 protein pathology in ALS and frontotemporal dementia-relevant preclinical models</a>.”
The findings add to previous evidence that ATH-115 <a href="https://alsnewstoday.com/news/als-mouse-model-sees-prolonged-survival-with-ath-1105/">extended lifespan</a> and <a href="https://alsnewstoday.com/news/ath-1105-aid-nerve-health-motor-skills-als-mouse-model/">improved motor function</a> in ALS mouse models.
“We are encouraged by the growing body of preclinical research supporting ATH-1105, which shows the molecule is protective against several [disease-causing mechanisms] common to ALS and FTD,” Kevin Church, PhD, Athira’s chief scientific officer, said in a <a href="https://www.globenewswire.com/news-release/2023/07/17/2705476/0/en/Athira-Pharma-Presents-Phase-2-Clinical-Data-Correlating-Improvements-in-Biomarkers-of-Neurodegeneration-and-Neuroinflammation-with-Improvements-in-Measures-of-Cognition-and-Functi.html">company press release</a>.
[recommended-reading id=85595]
<h3>Effects of ATH-1105 on ALS, FTD</h3>
Mutations in the TARDBP gene, which codes for TDP-43, have been linked to the risk of <a href="https://alsnewstoday.com/causes-of-als/">developing ALS</a>. The mutations cause the protein to fold into the wrong shape and form toxic clumps.
Nearly everybody (97%) with ALS grow these TDP-43 aggregates in motor neurons, the nerve cells that control voluntary movement and are progressively lost with the disease. The damage results in <a href="https://alsnewstoday.com/symptoms-of-als/#Muscular_symptoms">muscle weakness</a> and an inability to control movement. The aggregates also form in roughly half of people with FTD.
ATH-115 works as a <a href="https://www.athira.com/science/">positive modulator</a> of the HGF/MET system, meaning it activates it. The HGF/MET system is a signaling pathway that helps safeguard neurons from damage by promoting their growth, repair, and survival.
“Positive modulation of the HGF/MET system has been shown to protect against several drivers of neurodegeneration in preclinical models, and this approach may represent a potential therapeutic strategy for ALS and FTD,” wrote the researchers, who tested ATH-115 in lab-grown neurons from the hippocampus of healthy rats. The hippocampus is a brain region linked to memory and learning, and TDP-43 clumps <a href="https://alsnewstoday.com/news/study-links-cognitive-impairment-with-toxic-protein-clumps-in-als/">also build up there</a>.
Neurons treated with ATH-115 grew about twice as many neurites, or projections that form connections with other neurons, and about three times more synapses, which are the points of contact between them.
The effect had about the same magnitude as treatment with HGF, the growth factor in the HGF/MET system.
<h3>ATH-1105 offers protection</h3>
The scientists then used four chemicals in amounts that were toxic to lab-grown rat cortical neurons, or neurons from the brain’s outermost layer. The chemicals were the neurotransmitter glutamate, bacteria-derived lipopolysaccharide (LPS), hydrogen peroxide, and 1-methyl-4-phenylpyridinium, a neurotoxin.
Each of them reduced the number of neurons that remained alive. However, when treated with ATH-1105 beforehand, the neurons were protected against their associated damage and didn&#8217;t die as much. In fact, almost all remained alive.
The researchers then analyzed the effects of ATH-1105 when added to LPS-exposed lab-grown human macrophages, a type of immune cell. LPS exposure increased the cells’ production of IL-6 and TNF-alpha, two pro-inflammatory signaling molecules, while ATH-1105 significantly reduced their levels.
Inflammation induced by LPS can cause cognitive impairment. In mice, this can be studied using a test called a T-maze. Compared with a placebo, ATH-1105 (given by mouth once daily for 14 days) eased cognitive impairment in LPS-exposed mice.
Finally, the researchers used a mouse model of ALS and FTD that produces a faulty version of human TDP-43. Some mice were given ATH-1105 by mouth once daily from 1-3 months of age. Others were given a placebo.
Similar to data from previous preclinical studies, ATH-1105 reduced blood IL-6 and TNF-alpha levels. It also reduced the levels of neurofilament light chain, a marker of neuronal damage.
Moreover, ATH-1105 reduced TPD-43 levels in the mice’s sciatic nerve by about three times, nearly reaching those seen in healthy mice. The sciatic nerve is a long nerve that runs from the lower back down the lower limbs.
“The consistency and breadth of these effects in reducing markers of inflammation, neurodegeneration, and TPD-43 protein pathology continue to support the broad therapeutic potential and continued advancement of ATH-1105,” Church said.

ATH-1105 protects against common ALS, FTD disease mechanisms

<figure id="attachment_84106" aria-describedby="caption-attachment-84106" style="width: 271px" class="wp-caption aligncenter"><img loading="lazy" decoding="async" class="wp-image-84106 size-medium" src="https://alsnewstoday.com/wp-content/uploads/2023/05/Jodi-headshot-271x380.jpg" alt="Jodi O'Donnell-Ames" width="271" height="380" data-wp-pid="84106" /><figcaption id="caption-attachment-84106" class="wp-caption-text">Jodi O&#8217;Donnell-Ames founded Hope Loves Company after losing her husband to ALS. (Courtesy of Jodi O&#8217;Donnell-Ames)</figcaption></figure>
This is Jodi O&#8217;Donnell-Ames&#8217; story:
The term <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) was not a part of my vocabulary until May 1995. That&#8217;s when my husband, Kevin O&#8217;Donnell, was diagnosed with the disease at age 30. It was Memorial Day weekend and our world was turned upside down when those three letters were said to us. We drove home in tears and disbelief and had no idea how to share the news with our family, our friends, and our daughter, who was still a toddler.
Kevin and I began sharing our voices with the ALS community. We spoke before the U.S. Food and Drug Administration for the approval of the first ALS drug, <a href="https://alsnewstoday.com/rilutek-riluzole-for-als/">riluzole</a>, with Alina in our arms. The therapy was approved and our picture was featured in its marketing campaign. We also advocated for a change in the Medicare waiting period from 24 months to five months, which was also approved. Our story and involvement in that monumental decision is  preserved in the <a href="https://www.govinfo.gov/content/pkg/CREC-2000-12-15/pdf/CREC-2000-12-15-pt1-PgS11821-2.pdf#page=1">Congressional Record</a>.
Kevin battled ALS for five and a half years. In that time, I learned how to change a trach, operate a Hoyer lift, provide range of motion help, and survive on no sleep. Kevin proved to be courageous, strong, funny, and caring, but in February 2001 he lost his battle and we were left with no idea how to handle it.
<figure id="attachment_84107" aria-describedby="caption-attachment-84107" style="width: 253px" class="wp-caption aligncenter"><img loading="lazy" decoding="async" class="wp-image-84107 size-medium" src="https://alsnewstoday.com/wp-content/uploads/2023/05/Jodi-wearing-a-Hope-Loves-Company-hoodie-1-253x380.jpg" alt="Jodi O'Donnell-Ames" width="253" height="380" data-wp-pid="84107" /><figcaption id="caption-attachment-84107" class="wp-caption-text">Jodi O&#8217;Donnell-Ames founded Hope Loves Company to provide educational and emotional support to children and young adults who have a loved one who&#8217;s battling ALS. (Courtesy of Jodi O&#8217;Donnell-Ames)</figcaption></figure>
I got a job as the director of communications for the <a href="https://www.alshf.org/">ALS Hope Foundation</a> in Philadelphia and met Benton Ames, and his children, Nora and Adam. They&#8217;d also lost someone they loved to ALS. We married two years later and, in the midst of raising three children who&#8217;d lost a parent to ALS, the idea for <a href="https://www.hopelovescompany.com/">Hope Loves Company</a> (HLC) was born.
Hope Loves Company (HLC) is a 501c(3) nonprofit the mission of which is to provide educational and emotional support to children and young adults who&#8217;ve had or have a loved one battling ALS. We are celebrating its 10th anniversary!
 The organization offers numerous programs, all free of charge to families affected by ALS.
Camp HLC is a weekend overnight retreat for children and young adults. It&#8217;s an opportunity to have fun, participate in team-building exercises and meet other children. We also provide art and music therapy, healing circles facilitated by grief counselors, and opportunities for the children to open up in a comfortable, informal environment. Campers have fun and gain valuable coping techniques to face their continued challenges. The camp takes place in six states — New Jersey, Massachusetts, Indiana, Florida, Illinois, and California. We also offer Virtual Camp HLC.
Other offerings include: Hugs of Hope care packages, scholarships, ALS children&#8217;s books, online support sessions called HLC hangouts, and more. We are proud of the work we have accomplished in 10 years. To learn more, visit our website or call 609-730-1144.
In recognition of ALS Awareness Month in May, the ALS Community Spotlight campaign features a series of stories highlighting the real-life experiences of people affected by ALS, written in their own words. Follow us on <a href="https://www.facebook.com/alsnewstoday">Facebook</a> and <a href="https://www.instagram.com/alsnewstoday/">Instagram</a> for more stories like this, using the hashtag #ALSSpotlight, or read the full series.

To families affected by ALS, Hope Loves Company offers hope, support

A new technology powered by artificial intelligence (AI) may one day help doctors diagnose people in the early stages of <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), according to data from a clinical trial.
Developed by <a href="https://pisontechnology.com">Pison</a>, the technology was able to detect involuntary muscle twitches, or fasciculations, and changes in muscles&#8217; electrical activity that helps distinguish healthy people from people <a href="https://alsnewstoday.com/living-with-als/">with ALS</a>.
This means it could serve as a digital disease biomarker of ALS, helping patients start treatment earlier when it&#8217;s more effective at slowing disease progression. It could also let doctors monitor patients and see how well they&#8217;re responding to treatment.
“If these results are validated, then this will enable clinicians to detect motor neuron involvement noninvasively and track it over the course of disease and with treatment interventions,” Terry Heiman-Patterson, a professor of neurology and study lead investigator, said in a <a href="https://www.businesswire.com/news/home/20230418005133/en/Landmark-Study-Finds-Pison-AI-Technology-Can-Detect-Neurological-Disorder-in-ALS-Patients">Pison press release</a>.
[recommended-reading id=78444]
Muscle movement occurs when the brain sends electrical signals through specialized nerve cells called motor neurons. These signals can be measured via a technique known as electroneurography, which uses a biosensor, or a set of electrodes, in contact with the skin.
Pison developed a neural biosensor for the wrist that contains electrodes similar to those used in electroneurography, but allows for round-the-clock recording of electrical signals. Machine learning, a type of AI, then helps turn the recordings into information a computer can understand.
Because ALS damages motor neurons, electrical signals from the brain are weaker, which can help the algorithms distinguish ALS patients from healthy people, perhaps even before <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms of ALS</a> manifest.
“This technique may enable earlier diagnosis of motor neuron damage in presymptomatic gene carriers, help to detect motor neuron involvement in other disorders and provide a system that can remotely monitor progression in ALS and help in patient-centric clinical trial design,” said Heiman-Patterson, also the director of the MDA/ALS Center of Hope at Temple University.
The company is working to incorporate the technology into wearable devices, such as fitness trackers and smartwatches, which could help doctors collect information about motor neuron health and monitor their patients remotely. Having this technology in wearable devices also could help monitor the general population and potentially diagnose motor neuron-related conditions well before symptoms are evident.
“We have begun licensing our neural biosensor for incorporation into popular wearables such as smartwatches and fitness trackers for passive health monitoring, which will ultimately have the ability to track ALS and other neurological disorders in the form of neural health apps and telehealth services,” said John Croteau, CEO of Pison.
“New and better ways to diagnose and monitor people with ALS are urgently needed,” said Kuldip Dave, senior vice president of research at the <a href="https://www.als.org">ALS Association</a>, which funded the study, along with the <a href="https://www.nsf.gov">National Science Foundation</a>. “We are proud to have supported the initial testing of this promising new technology. We look forward to seeing the results of future studies to confirm and validate these findings with larger groups of participants.&#8221;
The company has announced plans to conduct larger and longer studies to better understand how well the technology can diagnose and and monitor the progression of ALS and other neurodegenerative diseases, such as <a href="https://multiplesclerosisnewstoday.com/multiple-sclerosis-overview/">multiple sclerosis</a> and <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson’s disease</a>.

Pison’s AI-powered technology may help identify early ALS

<a href="https://www.neurosense-tx.com/">NeuroSense Therapeutics</a> has joined researchers at Massachusetts General Hospital to study the impact of its investigational therapy PrimeC on key <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) processes.
The collaboration will the headed by Ghazaleh Sadri-Vakili, director of the Neuroepigenetics laboratory at the MassGeneral Institute for Neurodegenerative Disease. Using a new laboratory model generated from post-mortem brain tissue samples, the researchers seek to know more about PrimeC&#8217;s mechanisms of action in ALS.
&#8220;We are excited to join NeuroSense in its mission to advance PrimeC for people living with ALS,&#8221; Sadri-Vakili said in a <a href="https://www.prnewswire.com/news-releases/neurosense-therapeutics--massachusetts-general-hospitals-neuroepigenetics-lab-to-collaborate-on-elucidating-neurotherapeutic-effects-of-primec-in-als-301781895.html">company press release</a>. &#8220;Our in vitro model may serve as an effective tool to increase our understanding of PrimeC&#8217;s neurotherapeutic mechanism of action.&#8221;
PrimeC is an extended-release oral formulation that combines a fixed dose of the antibiotic ciprofloxacin and the anti-inflammatory celecoxib. Both are individually approved by the U.S. Food and Drug Administration and have established safety profiles.
The combination therapy is thought to target multiple disease processes in ALS, including iron accumulation, faulty RNA processing, inflammation, and motor nerve cell degeneration.
In a previous <a href="https://clinicaltrials.gov/ct2/show/NCT04165850">Phase 2a trial (NCT04165850)</a>, the original formulation of PrimeC markedly <a href="https://alsnewstoday.com/news/primec-safe-lowers-als-disease-biomarkers-phase-2-clinical-study/">reduced levels of ALS biomarkers</a> and showed trends toward lower disease progression rates and lung function declines compared with historical controls.
In particular, it <a href="https://alsnewstoday.com/news/primec-safe-lowers-als-disease-biomarkers-phase-2-clinical-study/">reduced the amount of TDP-43</a>, a protein that&#8217;s abnormal in most ALS cases, in neuron-derived exosomes (NDEs) — packets of cellular cargo released by nerve cells into the extracellular space.
As part of the new collaboration, Sadri-Vakili and her team will explore how PrimeC affects TDP-43 accumulation in patients. The scientists will also try to unravel how it works to reduce other disease mechanisms, including defects in autophagy (the process by which cells recycle faulty or unwanted molecules) and abnormalities in mitochondria, the cells energy-producing factories.
Its impact on oxidative stress, another ALS-related process caused by an imbalance between reactive oxygen-containing molecule production and the body&#8217;s ability to clear them, will also be investigated.
[recommended-reading id=78033]
<h3> Study to explore PrimeC&#8217;s effects on oxidative stress, mitochondrial defects</h3>
To address that, the researchers will use vesicles derived from nerve tissue from ALS patients and control subjects after death. The team has shown these vesicles can induce oxidative stress and mitochondrial defects in cell cultures.
They aim now to see how much these processes are impaired when cells are treated with the vesicles in the presence of PrimeC. They&#8217;ll also compare the effects of the individual components of PrimeC, celecoxib and ciprofloxacin, with those seen with the combination therapy.
“We are pleased to formally establish this important collaboration with Dr. Sadri-Vakili&#8217;s team, where we hope to elucidate PrimeC&#8217;s efficacy via key measurements that correlate with our Phase 2b ALS study endpoints,” said Shiran Zimri, PhD, vice president of research and development at NeuroSense.
PrimeC was granted orphan drug status in the U.S. in 2020 and in Europe the following year. The designation is given to potential treatments for rare diseases to accelerate their development and possible regulatory review.
The extended-release formulation of PrimeC is being investigated in the Phase 2b <a href="https://clinicaltrials.gov/ct2/show/NCT05357950">PARADIGM trial (NCT05357950)</a>. The trial is <a href="https://alsnewstoday.com/news/paradigm-trial-testing-als-therapy-primec-drops-u-s-sites/">enrolling about 69 patients</a>, ages 18-75, at multiple sites in Israel, Canada, Germany, and Italy.
In addition to standard ALS therapies, participants will be randomly assigned to receive PrimeC — two oral tablets twice daily for a total of 1,496 mg a day — or a placebo for six months.
The trial&#8217;s main goals are to determine the therapy&#8217;s safety and impact on disease biomarkers. Other, secondary measures include changes in the rate of disease progression, lung function and quality of life declines, and survival. Top-line data are expected later this year.

Collaboration to study PrimeC’s impacts on ALS disease mechanisms

A small Phase 2 clinical trial is evaluating the safety and tolerability of investigational treatment candidate EPI-589 in adults with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The <a href="https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2061210031">EPIC-ALS trial (jRCT2061210031)</a>, being conducted in Japan, will also assess exploratory effectiveness outcomes after six months of treatment. Data collection began in September 2021 and is expected to finish in October.
The trial&#8217;s design was recently described in, &#8220;<a href="https://www.researchprotocols.org/2023/1/e42032">An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study</a>,&#8221; which was published in <a href="https://jmirpublications.com/?__hstc=178719527.3ebc998c2f077e2b06b5464d7c63d5c3.1675280644317.1675280644317.1675280644317.1&amp;__hssc=178719527.2.1675280644317&amp;__hsfp=1616247428">JMIR Research Protocols</a>. 
EPI-589, also called (R)-troloxamide quinone, is a brain-penetrant small molecule given orally that&#8217;s designed to reduce oxidative stress, a type of cellular death implicated in the progression of ALS and other neurodegenerative diseases.
Oxidative stress is marked by an imbalance between toxic reactive oxygen species and the antioxidant defense systems needed to fight them.
The treatment works to boost or speed up processes involved in controlling oxidative stress and enhance energy metabolism in cells&#8217; mitochondria, the cellular energy production centers that become dysfunctional in ALS.
It was originally developed by BioElectron Technology Corporation (previously Edison Pharmaceuticals) for inflammatory neurodegenerative diseases, including ALS and <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson&#8217;s disease</a>. Under an agreement with BioElectron, <a href="https://www.sumitomo-pharma.com/">Sumitomo Pharma</a> holds the licensing rights for EPI-589 in Japan and North America and is providing the EPI-589 to be used in the trial. BioElectron was <a href="https://www.spglobal.com/marketintelligence/en/news-insights/trending/9pIzMOZy1PRAYMOnz6uCKA2">acquired</a> by PTC Therapeutics in 2019.
In ALS cell models, EPI-589 was <a href="https://www.tandfonline.com/doi/pdf/10.1080/21678421.2019.1646991">more potent</a> than edaravone — sold as <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a>, an approved ALS treatment with an antioxidant mechanism — at protecting against oxidative stress and mitochondrial dysfunction.
Additional preclinical studies showed dose dependent effects of EPI-589 on <a href="https://www.biorxiv.org/content/10.1101/2022.03.13.484182v1">slowing motor deterioration in an ALS mouse model</a>, where it also reduced biomarkers of oxidative stress and nerve cell damage.
A Phase 1 study <a href="https://accp1.onlinelibrary.wiley.com/doi/10.1002/cpdd.1146">found</a> EPI-589 at doses up to 1,500 mg per day to be well tolerated in healthy adults, prompting the launch of a <a href="https://clinicaltrials.gov/ct2/show/NCT02460679">Phase 2 trial (NCT02460679)</a>, which evaluated its safety in 19 adults with ALS.
The <a href="https://alsnewstoday.com/news/epi-589-shows-positive-results-als-patients-phase-2a-trial/">results showed</a> EPI-589 at a dose of 500 mg twice per day was safe and well tolerated.
Signs of clinical effectivenesss were also observed, including a reduction in disease-associated biomarkers in the blood and the cerebrospinal fluid (CSF), which surrounds the brain and spinal cord.
Results also suggested EPI-589 may slow disease progression, as assessed with the ALS Functional Rating Scale-Revised (ALSFRS-R), and lead to improvements in grip strength and swallowing.
[recommended-reading id=80592]
<h3>Clinical trial to test EPI-589&#8217;s safety, tolerability</h3>
The ongoing exploratory Phase 2 trial seeks to evaluate EPI-589&#8217;s safety and tolerability at a dose of 500 mg three times a day among 10 adults with ALS. Participants are being recruited from three centers in Japan.
Eligible participants, ages 18-79, have had an onset of ALS within 1.5 years of screening. Patients on <a href="https://alsnewstoday.com/als-treatment/rilutek-riluzole/">Rilutek</a> (riluzone) must be on a stable dose and regimen for at least a month before enrolling. Using other medications that may also have an antioxidant mechanism, such as Radicava, is not permitted.
The trial will last 40 weeks — a 12 week run-in period, 24 weeks (six months) of treatment, and a four week follow-up. The run-in period is designed to assess each patient&#8217;s baseline clinical status before treatment.
During the treatment phase, patients will take 500 mg EPI-589 — two 250 mg oral tablets — three times a day at least an hour before eating.
The trial&#8217;s main goal is safety, which will be evaluated with side effects, lab tests, vital signs, heart tests, and monitoring for suicidality.
Disease progression will be monitored by a change in ALSFRS-R scores as well as time to death, tracheostomy, or use of whole-day ventilation support. Additional physical findings will include tests of lung function, muscle strength, functional ability, and health-related quality of life.
Blood and CSF biomarkers, including markers of oxidative stress and nerve cell damage will also be assessed, as will MRI disease markers.
&#8220;As the primary objective of this trial is to evaluate safety and tolerability, placebo-controlled trials will be needed to confirm the efficacy,&#8221; the researchers wrote. &#8220;This pilot trial will provide insights into the variability of efficacy endpoints and the feasibility of the next large randomized controlled trial.&#8221;

Tag: amyotrophic lateral sclerosis (ALS)