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In most cases of <a href="https://alsnewstoday.com/?page_id=9613">amyotrophic lateral sclerosis</a> (ALS), dysfunction of a protein known as TDP-43 leads to abnormally low levels of another protein, stathmin-2, which is sufficient to drive nerve cell dysfunction, new data suggest.
In an aim to restore stathmin-2 levels, researchers created a designer DNA treatment. Now, that experimental therapy has shown promise in early mouse studies.
Results from the research were shared by Clotide Lagier-Tourenne, MD, PhD, a professor at Massachusetts General Hospital and Harvard Medical School, at the Muscular Dystrophy Association&#8217;s MDA Clinical &amp; Scientific Conference, held March 19-22 in Dallas and virtually. The talk was titled &#8220;Stathmin-2: an emerging therapeutic target in TDP-43 proteinopathies.&#8221;
The data also were detailed in the study, &#8220;<a href="https://www.science.org/doi/10.1126/science.abq5622">Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies</a>,&#8221; which was published in <a href="https://www.science.org/journal/science">Science</a>.
&#8220;Our findings lay the foundation for a clinical trial to delay paralysis in ALS by maintaining stathmin-2 protein levels in patients using our designer DNA drug,&#8221; Don Cleveland, PhD, a professor at the University of California San Diego (UCSD) and co-author of the study, said in a <a href="https://today.ucsd.edu/story/dna-treatment-could-delay-paralysis-that-strikes-nearly-all-patients-with-als">university press release</a>.
[recommended-reading id=78093]
<h3>Creating a designer DNA therapy to restore stathmin-2</h3>
Nearly all cases of ALS are characterized by abnormalities with the protein TDP-43. Normally, TDP-43 is located in the nucleus, the cellular compartment that houses DNA, but in ALS, the protein moves outside of the nucleus, disrupting its normal function.
TDP-43 has long been known to be involved in processing messenger RNA (mRNA) — an intermediary molecule made when genes are read to make protein. In particular, TDP-43 plays essential roles in mRNA splicing.
Within a cell&#8217;s DNA, genes contain exons — the parts of the genetic code that have instructions for making proteins — that are interspersed with introns. While introns don&#8217;t provide instructions for making protein, they have other regulatory functions.
When a gene is read, the entire sequence normally is copied over into mRNA, and then the mRNA undergoes splicing to remove all the introns and string the exons together. The final mature mRNA sequence is then sent to the cell&#8217;s protein-making machines, which can read the code to make protein.
&#8220;Now, as a field, we know that TDP-43 binds thousands of targets, and actually leads to hundreds if not thousands of RNA alterations and RNA splicing,&#8221; Lagier-Tourenne said.
In cell experiments, the researchers showed that reducing TDP-43 levels leads to a change in splicing for the gene STMN2, which provides instructions for making the protein stathmin-2. Specifically, the lack of TDP-43 led to the inclusion of an extra sequence called a cryptic exon, which is normally removed from the mature code.
The researchers showed that TDP-43 normally binds to the cryptic exon sequence, preventing it from being included in the mature mRNA. Without TDP-43, the cryptic exon gets included in the mature sequence, but other exons get left out, resulting in a shortened mRNA that cannot be used to produce the stathmin-2 protein. The end result is that dysfunctional TDP-43 leads to reduced levels of stathmin-2.
In their study, the team found high levels of the shortened STMN2 mRNA containing the cryptic exon in spinal cord samples from people with <a href="https://alsnewstoday.com/sporadic-als/">sporadic ALS</a>. However, the abnormal mRNA was not present in people without ALS. Consistently, levels of stathmin-2 protein were decreased in the sporadic ALS patients, but not in spinal cords unaffected by ALS.
The abnormal mRNA also was present in people with ALS caused by mutations in the C9ORF7 gene, which is known to cause TDP-43 abnormalities. However, patients with mutations in the gene SOD1 — a rare genetic form of ALS that typically doesn&#8217;t cause abnormalities with TDP-43 — did not have the abnormal mRNA.
[recommended-reading id=81458]
<h3>Designer DNA drug is similar to therapy for spinal muscular atrophy</h3>
The stathmin-2 protein is known to play roles in providing structural support to nerve cells and axons — the long fibers that nerves use to connect with each other. The researchers showed that motor neuron cells lacking stathmin-2 were unable to regrow after an axon injury. Cells lacking TDP-43 and, consequently, with low stathmin-2 levels, also were not able to regrow.
However, when the researchers engineered cells lacking TDP-43 so that they could express higher levels of stathmin-2 protein, the cells&#8217; ability to regrow was restored.
&#8220;What was very surprising was that, in these motor neurons where we have TDP-43 knock-down, we know there are hundreds if not thousands of [RNA] expression and splicing alterations, and restoring stathmin-2 was sufficient to completely rescue the regeneration ability of these motor neurons,&#8221; Lagier-Tourenne said.
In mice, reducing levels of stathmin-2 in the nervous system led to progressive motor weakness and dysfunction, with poorer connections between nerve and muscle cells. These findings collectively implied that increasing stathmin-2 levels could be therapeutic in ALS.
[quote align=&#8221;center&#8221;]Our findings lay the foundation for a clinical trial to delay paralysis in ALS by maintaining stathmin-2 protein levels in patients using our designer DNA drug.[/quote]
The researchers created a designer DNA drug, called an antisense oligonucleotide, which basically aims to mimic the function of TDP-43, thereby correcting splicing of STMN2 mRNA and restoring production of stathmin-2 protein.
A similar type of therapy is approved in the U.S. and other countries to treat <a href="https://smanewstoday.com/what-is-spinal-muscular-atrophy/">spinal muscular atrophy</a>, a genetic disorder that, like ALS, affects motor neurons.
&#8220;What we have now found is that we can mimic TDP-43 function with a designer DNA drug, thereby restoring correct stathmin-2 RNA and protein level in the mammalian nervous system,&#8221; Cleveland said.
To test the experimental therapy, the researchers used mice engineered to express a version of the human STMN2 gene that lacked sites for TDP-43 to bind — meaning that these mice always produced the abnormal, truncated mRNA, and had low stathmin-2 levels as a result. Treatment with the experimental DNA therapy restored stathmin-2 levels.
&#8220;With mouse models we engineered to misprocess their stathmin-2 encoding RNAs, like in these human diseases, we show that administration of one of these designer DNA drugs into the fluid that surrounds the brain and spinal cord restores normal stathmin-2 levels throughout the nervous system,” Cleveland said.

MDA 2023: Designer DNA drug for ALS shows promise in mouse studies

On average, a person with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) will require a wheelchair to get around within two years of the initial onset of <a href="https://alsnewstoday.com/symptoms-of-als/">disease symptoms</a>.
Findings underscore the condition&#8217;s rapid advance, and the need for new <a href="https://alsnewstoday.com/als-treatment/">ALS treatments</a> that work to slow disease progression, its researchers noted.
&#8220;Effective therapies that slow down disease progression may have the potential to reduce [the] humanistic burden of ALS and would help patients, physicians, and caregivers to plan better around these transitions and spread out the costs over time,&#8221; they wrote.
These data were shared at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, taking place March 19-22 in Texas, in the poster, &#8220;<a href="https://www.mdaconference.org/abstract-library/time-from-amyotrophic-lateral-sclerosis-onset-to-key-disease-milestones-analysis-of-patient-data-from-a-real-world-cross-sectional-survey/">Time From Amyotrophic Lateral Sclerosis Onset to Key Disease Milestones: Analysis of Patient Data From a Real-World Cross-Sectional Survey</a>.&#8221;
[recommended-reading id=82887]
<h3>Estimates of average time of ALS progression based on neurologist survey</h3>
<a href="https://alsnewstoday.com/causes-of-als/">ALS is caused</a> by the death and dysfunction of motor neurons, the specialized nerve cells that control movement, resulting in muscle weakness that eventually progresses to paralysis. It tends to progress very quickly, though considerable variation among patients can be seen.
To better understand ALS progression given current approaches, scientists led by a team at <a href="https://cytokinetics.com/" rel="nofollow">Cytokinetics</a> analyzed information from the Adelphi ALS Disease Specific Programme, which surveyed neurologists in the U.S. and several European countries: France, Germany, Italy, Spain, and the U.K.
The analysis included data covering 1,003 ALS patients — 379 in the U.S. and 624 in Europe — collected between July 2020 and March 2021. About two-thirds of the patients were male, and the vast majority were white.
Most patients in Europe (82.5%) were on treatment with riluzole (sold as <a href="https://alsnewstoday.com/als-treatment/rilutek-riluzole/">Rilutek</a> and other formulations), while most U.S. patients (78.1%) were being treated with riluzole and/or <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> (edavarone), which is not available in Europe.
Among all the patients, 3.9 months was the average time from initial awareness of symptoms to a first medical visit. The average time from symptom onset to <a href="https://alsnewstoday.com/als-diagnosis/">ALS diagnosis</a> was eight months.
At about 1.5 years after disease onset, the average patient started to require a walking aid like a cane or walker. Around this time, these people also tended to experience changes in employment and require more caregiving.
On average, the time to needing a wheelchair was slightly less than 23 months after disease onset. Between 24.6 months and 28.6 months after onset, on average, patients required medical intervention to help them communicate, eat, and breathe. The average time before they needed the care of a specialized facility was slightly more than 30 months.
&#8220;Patients rapidly transitioned through various disease milestones, which demonstrates the rapid progression of ALS,&#8221; the researchers wrote in their abstract.
Comparisons of patients by where they lived showed that U.S. patients tended to be diagnosed earlier, by nearly four months on average. However, patients in the U.S. also tended to hit other disease milestones (e.g., needing a walking aid, caregiver support, or wheelchair) earlier than their European counterparts.
Because these data were based on neurologists&#8217; reports about their patients at a single point in time, the researchers stressed that caution is needed in interpreting these differences. Findings, they noted, contained &#8220;limited information about individual patient journeys or disease history.&#8221;

MDA 2023: Patients typically need wheelchairs within 2 years of onset

A potential new genetic risk factor for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) has been discovered by researchers at the University of Washington.
The scientists say a mutation in which a region of the WDR7 gene is repeated more times than usual may increase the risk of ALS.
“We believe that this expansion acts as a genetic modifier to disease susceptibility, as in the repeat on its own doesn’t cause disease, but it functions in conjunction with other genetic risk factors,” Samuel Smukowski, a graduate student at the University of Washington, said in a talk at the Muscular Dystrophy Association&#8217;s MDA Clinical &amp; Scientific Conference, held in Texas and virtually March 19 through 22.
Smukowski’s talk was titled “<a href="https://www.mdaconference.org/abstract-library/functional-consequences-of-a-human-specific-tandem-repeat-in-wdr7-associated-with-als/">Functional consequences of a human-specific tandem repeat in WDR7 associated with ALS</a>.”
[recommended-reading id=82805]
<h3>More than 50 VNTR expansions have been linked to neurological diseases</h3>
The human genome contains instructions for making all of the proteins needed for the body to function. Within the genome, there are many areas called variable number tandem repeats, or VNTRs, where a particular sequence of nucleotides (the building blocks of DNA) gets repeated over and over.
A VNTR expansion is a type of mutation where a VNTR sequence has many more repeats than normal. More than 50 VNTR expansions have been linked to neurological diseases, and a mutation of this type in the gene C9ORF72 is the most common <a href="https://alsnewstoday.com/als-and-genetics/">ALS-associated mutation</a>.
Smukowski and his colleagues initially assessed data from a family affected by <a href="https://alsnewstoday.com/forms-of-als/familial-als/">familial ALS</a>. Using cutting-edge genetic sequencing technology, the team discovered a previously unreported 69-nucleotide-long VNTR sequence in the gene WDR7.
A VNTR expansion in this gene, which provides instructions for making a protein that’s involved in the function of synapses (the connections between nerve cells), appeared to be associated with ALS in the family.
Analyses of data from more than 900 people in three groups of <a href="https://alsnewstoday.com/forms-of-als-2/sporadic-als/">sporadic ALS</a> patients — one from the Answer ALS program, one from Quebec, and a third from the Coriell Institute for Medical Research — showed that ALS patients more commonly had an expanded VNTR region in the WDR7 gene compared with people who did not have ALS.
&#8220;ALS patients disproportionately have longer repeat expansions,&#8221; Smukowski said.
[quote=&#8221;center&#8221;]We believe that this expansion acts as a genetic modifier to disease susceptibility, as in the repeat on its own doesn’t cause disease, but it functions in conjunction with other genetic risk factors.[/quote]
When WDR7 and other protein-coding genes are &#8220;read&#8221; to produce a protein, the genetic code is copied over into a temporary molecule called messenger RNA (mRNA). Some ALS-associated mutations are known to cause mRNA and proteins to clump up inside cells, which is thought to be toxic and contribute to the nerve cell degeneration that drives ALS.
The researchers showed that mRNA from the WDR7 gene harboring an expansion in the VNTR region was found in clumps alongside the ALS-linked protein TDP-43.
The team also showed that the repeat region could be used by cells to produce microRNAs, which are regulatory RNA molecules that bind to the mRNAs of certain proteins to reduce their levels. The larger the expansion in the WDR7 VNTR region, the more microRNAs were produced, the research showed.
In theory, this could mean that the VNTR expansion could change the levels of specific proteins in cells, ultimately dysregulating cellular activity.
[recommended-reading id=82220]
Smukowski noted that several of the genes known to be regulated by these microRNAs have important roles in neurological function, with mutations in one gene, called VPS53, having been shown to spontaneously lead to ALS in mice.
&#8220;Therefore it’s possible that a high copy number of this repeat expansion is interfering with these target genes’ normal expression,&#8221; he said.
“Our findings underscore the biological impact of tandem repeat expansions in modulating susceptibility to ALS,” the scientists wrote in their abstract.
They are continuing work to understand how this WDR7 mutation, and other VNTR expansions, may affect the development and progression of ALS.

MDA 2023: Expansion in WDR7 gene linked to increased ALS risk

Four people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) each experienced a marked slowing in disease progression with COYA 302, an experimental immune-modulating therapy tested in a small proof-of-concept clinical trial, according to <a href="https://www.coyatherapeutics.com/">Coya Therapeutics</a>, its developer.
Based on these findings, Coya is planning to start work on further trials to test the therapy candidate in larger groups of ALS patients. Pending regulatory approvals, the company hopes to begin Phase 1b/2 clinical testing later this year or early next year.
&#8220;We believe the results of this initial proof-of-concept study in a small number of ALS patients are encouraging and warrant conducting a larger and controlled industry-sponsored study,&#8221; Adrian Hepner, MD, chief medical officer of Coya, said in a <a href="https://www.businesswire.com/news/home/20230321005042/en/Coya-Therapeutics-Inc.-Announces-Positive-Results-from-a-Proof-of-Concept-Academic-Clinical-Study-for-COYA-302-in-Amyotrophic-Lateral-Sclerosis-ALS">company press release</a>.
Stanley Appel, MD, chair of Coya’s scientific advisory board and a trial investigator at Houston Methodist Research Institute, in Texas, shared the study&#8217;s findings at the Muscular Dystrophy Association&#8217;s MDA Clinical &amp; Scientific Conference, held March 19-22 in Dallas. His talk was titled, &#8220;Novel Treg-modulating Immunotherapy Targets Inflammation in ALS.&#8221; The work was funded in part by Coya.
[recommended-reading id=77518]
<h3>Seeking to slow disease progression in ALS</h3>
COYA 302 contains a combination of the immune signaling molecule IL-2 and a fusion protein known as CTLA4-Ig or abatacept. It is administered via subcutaneous (under-the-skin) injection.
The therapy is designed to reduce inflammation by increasing the activity of regulatory T-cells — a type of anti-inflammatory immune cells known as Tregs — while simultaneously decreasing the activity of pro-inflammatory immune cells
Inflammation in the nervous system, termed neuroinflammation, is &#8220;an extremely important part in propagating neuronal injury in ALS,&#8221; Appel said.
Coya recently forged an agreement with a global pharmaceutical company known as Dr. Reddy’s Laboratories for the production of COYA 302. Under the agreement, Coya will produce the IL-2 component of the therapy — which the company is also developing separately under the name COYA 301 — while Dr. Reddy&#8217;s will provide the CTLA4-Ig part of COYA 302.
&#8220;We believe that the combined resources of both organizations strengthens our chances to bring this therapeutic modality to patients with neurodegenerative diseases if approved by regulatory authorities,&#8221; Howard Berman, PhD, Coya&#8217;s CEO, said in a <a href="https://www.businesswire.com/news/home/20230317005028/en/Coya-Therapeutics-Inc.-Announces-an-Agreement-with-Dr.-Reddy%E2%80%99s-Laboratories-Ltd.-to-License-its-proposed-biosimilar-Abatacept-for-the-Development-and-Commercialization-of-COYA-302-for-the-Treatment-of-Neurodegenerative-Diseases">press release</a> announcing the agreement.
In the proof-of-concept clinical trial, four ALS patients were treated with COYA 302 for 48 weeks, or about one year. The participants then were followed for an additional eight weeks (about two months) after they stopped receiving the medication.
The therapy was generally well tolerated, with no serious side effects reported. The most common side effects were injection site reactions that were mostly rated as mild.
&#8220;Safety and tolerability went very very well in these patients,&#8221; Appel said, noting that the injection reactions seen were similar to reactions that are common with other injectable therapies like insulin.
[recommended-reading id=71573]
<h3>ALS progression slowed, ALSFRS-R scores show</h3>
The participants&#8217; symptom severity and functional abilities were measured with the ALS Functional Rating Scale (ALSFRS-R), in which higher scores indicate a better ability to function. Prior to starting the study, the participants&#8217; ALSFRS-R scores were decreasing at a rate of about 1.1 points per month on average.
At the start of the study (baseline), the average ALSFRS-R score was 33.5 points. Halfway through the study, at week 24, the average score was stable at 33.75 points. After 48 weeks of treatment, the average score had declined less than two points to 32. The difference in scores from the start of the trial to its end was not statistically significant.
These results indicate that ALS progression was slowed considerably while patients were receiving treatment with COYA 302. However, after treatment with COYA 302 stopped, patients showed rates of disease progression resembling those before treatment, going from 32 points in the ALSFRS-R scale to 30 in about eight weeks.
&#8220;The average patient decline, as measured by ALSFRS-R, is approximately -1-point/month. In the present study there was no average decline from baseline to 24 weeks and we observed minimal average decline from baseline to 48 weeks,&#8221; Appel said.
&#8220;To us, this was truly exciting to go 48 weeks and have the patients doing as well as they were, with good safety and good tolerability,&#8221; he said.
[quote align=&#8221;center&#8221;]We believe the results of this initial proof-of-concept study in a small number of ALS patients are encouraging and warrant conducting a larger and controlled industry-sponsored study.[/quote]
Analyses of immune cell function indicated that the therapy was working as designed: data suggested that Treg activity increased during the 48 weeks of treatment with COYA 302, then decreased again once patients were off the therapy. Other markers of inflammation and oxidative stress — a type of cell damage associated with inflammation — also decreased with COYA 302 treatment.
&#8220;The therapy was well tolerated, and most significantly it enhanced [Treg] suppressive functions, suppressed markers of oxidative stress, and ameliorated disease progression over 48 weeks,&#8221; Appel said. He added that these findings suggest COYA 302 &#8220;may provide a potentially meaningful approach for the &#8216;unmet need&#8217; in ALS.&#8221;
Appel stressed that further studies will be needed to conclusively evaluate the efficacy of COYA 302.
But he added, &#8220;We&#8217;re very excited about where we are as the preliminary proof of concept.&#8221;
Coya also is developing a cell therapy called COYA 101, in which Treg cells are administered as a form of treatment. Data from early trials of that therapy also have suggested <a href="https://alsnewstoday.com/news/coya-treg-therapy-als001-als-reduces-inflammation-early-trial/">reductions in oxidative stress</a> and <a href="https://alsnewstoday.com/news/treg-therapy-found-safe-effective-slowing-als-small-trial/">slower ALS disease progression</a>.

MDA 2023: COYA 302 therapy slows ALS progression in early trial

<a href="https://alsnewstoday.com/what-is-als/">Amyotrophic lateral sclerosis</a> (ALS) patients treated with <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> (edaravone) tend to go longer before reaching disease milestones such as needing a walking aid or breathing support, according to an analysis of insurance data.
The findings were presented at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference in the poster, &#8220;<a href="https://www.mdaconference.org/abstract-library/longer-milestone-free-time-in-iv-edaravone-treated-vs-iv-edaravone-naive-amyotrophic-lateral-sclerosis-patients-an-administrative-claims-analysis/">Longer Milestone-free Time in IV Edaravone-treated vs IV Edaravone-naïve Amyotrophic Lateral Sclerosis Patients: An Administrative Claims Analysis</a>.&#8221; The work was funded by <a href="https://www.mt-pharma-america.com/">Mitsubishi Tanabe Pharma America</a> (MTPA), which markets Radicava in the U.S.
Radicava is an <a href="https://alsnewstoday.com/als-treatment/">approved treatment</a> for ALS that&#8217;s thought to work by decreasing oxidative stress, a type of cellular damage that contributes to nerve cell death. It&#8217;s administered via infusion into the bloodstream, but an oral formulation called Radicava ORS has been approved in the U.S. MTPA <a href="https://www.prnewswire.com/news-releases/mitsubishi-tanabe-pharma-america-announces-more-than-10-000-people-with-als-treated-with-radicava-ors-edaravone-andor-radicava-edaravone-301773547.html">recently announced</a> that more than 10,000 people in the U.S. have received one of the two formulations.
A team of scientists at MTPA and other institutions analyzed data from a large U.S. insurance database between 2017-2021. The analysis only included patients with commercial insurance or Medicare Advantage plans, so it may not represent all ALS patients, the researchers noted.
The researchers examined 360 patients treated with Radicava for a median of 9.1 months and an equal number of patients who weren&#8217;t given Radicava. The two groups were matched based on available data so they were comparable for age, race, gender, and disease duration.
[recommended-reading id=82739]
<h3>Comparing outcomes of Radicava treatment</h3>
To compare outcomes between them, the researchers calculated a statistical measure called restricted mean time lost (RMTL), which represents the average amount of time lost due to a certain milestone. For instance, a lower RMTL for death would suggest longer survival times. The researchers specifically assessed the first year after patients were entered into the database.
Results showed, for both commercially insured and Medicare Advantage patients, the RMTL for requiring a walking aid (such as a cane, walker, or wheelchair) was lower for those given Radicava, suggesting treated patients retained their ability to walk independently longer.
Radicava-treated patients also had lower RMTLs for noninvasive ventilation, using artificial nutrition, and hospice care. RMTLs were significantly higher among Radicava-treated patients for invasive ventilation or speech-generating devices, however.
The researchers also compared survival outcomes in the first and second year after patients were enrolled in the database. Results showed, for those who didn&#8217;t receive Radicava, mortality rates were 69.9% in the first year and 77.3% in the second. By contrast, mortality rates were 40.4% and 47% in the first and second years respectively for patients on Radicava.
These results &#8220;provide an example of real-world impact of [Radicava] in patients with ALS,&#8221; the scientists said, adding the findings &#8220;may be useful to payers and clinicians in evaluating the use of [Radicava].&#8221;
Both Radicava and Radicava ORS are administered in 28-day cycles of 14 days on treatment, followed by 14 days off. MTPA is currently running a Phase 3 clinical trial called <a href="https://clinicaltrials.gov/ct2/show/NCT04569084">MT-1186-A02 (NCT04569084)</a> to compare alternative dosing regimes of Radicava ORS.
Results are expected later this year. Scientists at MTPA and other institutions shared details of the trial&#8217;s design at the MDA conference in the poster, &#8220;<a href="https://www.mdaconference.org/abstract-library/phase-3b-study-to-evaluate-efficacy-and-safety-of-oral-edaravone-over-48-weeks-in-patients-with-amyotrophic-lateral-sclerosis-mt-1186-a02/">Phase 3b Study to Evaluate Efficacy and Safety of Oral Edaravone Over 48 Weeks in Patients with Amyotrophic Lateral Sclerosis (MT-1186-A02)</a>.&#8221;
The trial intends to enroll about 380 adults with ALS whose disease began within two years of enrollment. Participants will be randomly assigned to one of two groups and treated for about a year.
In one group, participants will be treated with Radicava ORS (105 mg) every day, rather than taking 14 days off treatment in each 28-day cycle. In the second group, participants will first get Radicava ORS for 14 days, then a placebo for 14 days (mimicking the currently approved schedule) for one 28-day-cycle. For the next 11 cycles, participants will take the therapy for 10 days and a placebo for 18 days.
The main goal is to compare outcomes on the ALS Functional Rating Scale Revised (ALSFRS-R), a standardized measure of ALS symptom severity. Secondary measures include changes in lung function, survival, and quality of life.
After completing the main trial, participants will be able to enter an open-label extension and receive Radicava ORS for an extended period.
&#8220;This study will provide important information on the safety, efficacy, and tolerability of 2 dosing regimens for [Radicava ORS] in patients with ALS,&#8221; the researchers concluded in their poster.
&#8220;These presentations reflect our determination to not only broaden our expertise in ALS, but to continue sharing key insights that have a meaningful impact on the patient and medical communities,&#8221; Gustavo A. Suarez Zambrano, MD, vice president of medical affairs at MTPA, said in a <a href="https://www.prnewswire.com/news-releases/mitsubishi-tanabe-pharma-america-announces-presentations-in-als-at-2023-mda-clinical--scientific-conference-301774776.html">company press release</a>.

Tag: MDA 2023

MDA 2023: Designer DNA drug for ALS shows promise in mouse studies

MDA 2023: Patients typically need wheelchairs within 2 years of onset

MDA 2023: Expansion in WDR7 gene linked to increased ALS risk

MDA 2023: COYA 302 therapy slows ALS progression in early trial

MDA 2023: Walking, other functions retained longer on Radicava